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Section editor transclusions Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: regimens tested in specific populations have been moved to dedicated pages:

88 regimens on this page 145 variants on this page

Guidelines

ASH

2020: Sekeres et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

ELN

2022: Döhner et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN

Older

2017: Döhner et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
2010: Döhner et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet

ESMO

2020: Heuser et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Older

2013: Fey et al. Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

"How I Treat"

2020: DeWolf & Tallman How I treat relapsed or refractory AML
2020: DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020 Jan 9;135(2):85-96. link to original article PubMed
2016: Ofran Y, Tallman MS, Rowe JM. How I treat acute myeloid leukemia presenting with preexisting comorbidities. Blood. 2016 Jul 28;128(4):488-96. Epub 2016 May 27. link to PMC article PubMed
2015: Röllig C, Ehninger G. How I treat hyperleukocytosis in acute myeloid leukemia. Blood. 2015 May 21;125(21):3246-52. Epub 2015 Mar 16. link to original article PubMed
2014: Ossenkoppele G, Löwenberg B. How I treat the older patient with acute myeloid leukemia. Blood. 2015 Jan 29;125(5):767-74. Epub 2014 Dec 16. link to original article PubMed

NCCN

NCCN Guidelines - Acute Myeloid Leukemia

Antifungal prophylaxis

2022: Stemler et al. Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association

Older

2015: Halpern et al. Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia

Upfront induction therapy, standard and older "fit" patients

These are aggressive remission induction regimens given with curative intent.

7+3d (standard-dose)

7+3d: 7 days of cytarabine + 3 days of daunorubicin
AD: Ara-C (Cytarabine) & Daunorubicin
DA: Daunorubicin & Ara-C (Cytarabine)

Regimen variant #1, 700/135 (CI Ara-C)

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Yates et al. 1973	NR in abstract	Non-randomized, <20 pts (RT)
Rai et al. 1981 (CALGB 7421)	1974-1975	Phase 3 (E-esc)	1. 7+3d; bolus Ara-C)	Seems to have superior CR rate
			2. 5+2d	Superior CR rate
			3. 5+2d; bolus Ara-C	Superior CR rate
Omura et al. 1982	1974-1975	Phase 3 (E-de-esc)	1. AVML	Not directly compared
Omura et al. 1982	1974-1975	Phase 3 (E-de-esc)	2. TAD	Superior time to CR
Yates et al. 1982 (CALGB 7721)	1977-1979	Phase 3 (C)	1. 7+3d (low-dose)	Did not meet efficacy endpoints
Yates et al. 1982 (CALGB 7721)	1977-1979	Phase 3 (C)	2. 7+3a; 30 mg/m²	Did not meet efficacy endpoints
Vogler et al. 1984	1977-1981	Non-randomized portion of RCT
Preisler et al. 1987 (CALGB 7921)	1979-1982	Phase 3 (C)	1. 10+3d	Did not meet primary endpoint of CR rate
Preisler et al. 1987 (CALGB 7921)	1979-1982	Phase 3 (C)	2. TAD	Did not meet primary endpoint of CR rate
Stein et al. 1990	1982-1985	Phase 3 (C)	MA	Did not meet primary endpoint of CR rate
Arlin et al. 1990	NR in abstract	Phase 3 (C)	7+3m	Did not meet efficacy endpoints
Dillman et al. 1991 (CALGB 8321)	1982-1986	Phase 3 (C)	7+3d; higher-dose Ara-C	Did not meet primary efficacy endpoints
Wiernik et al. 1992	1985-1989	Phase 3 (C)	7+3i	Seems to have inferior OS
Vogler et al. 1992	1985-1989	Phase 3 (C)	7+3i	Seems to have inferior CR rate
Rowe et al. 2004 (ECOG E3993)	1993-1997	Phase 3 (C)	1. 7+3d & GM-CSF 2. 7+3i 3. 7+3i & GM-CSF 4. 7+3m 5. 7+3m & GM-CSF	Did not meet primary endpoint of CR rate
Latagliata et al. 2008 (GIMEMA GSI 103 AMLE)	2001-2004	Phase 3 (C)	7+3 (Daunoxome)	Did not meet primary endpoint of CR rate
Cripe et al. 2010 (ECOG E3999)	2002-2005	Phase 3 (C)	7+3d & Zosuquidar	Did not meet primary endpoint of OS
Fernandez et al. 2009 (ECOG E1900)	2002-2008	Phase 3 (C)	7+3d; high-dose	Inferior OS
Dombret et al. 2015 (AZA-AML-001)	2010-2014	Phase 3 (C)	Azacitidine	Might have inferior OS

Note: this was the lower bound of the allowable daunorubicin dose in AZA-AML-001.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 45 mg/m² IV once per day on days 1 to 3

7-day course

Subsequent treatment

ECOG E3993, patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of 7+3i

Regimen variant #2, 700/150 (CI Ara-C)

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bishop et al. 1990	1984-1987	Phase 3 (C)	ADE; standard-dose	Did not meet endpoint of OS

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 50 mg/m² IV bolus once per day on days 1 to 3

7-day course

Regimen variant #3, 1120/120 (intermittent Ara-C)

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Masaoka et al. 1996	NR in abstract	Randomized Phase 2 (E-switch-ic)	7+3i	Seems to have inferior CR rate

Chemotherapy

Cytarabine (Ara-C) 80 mg/m² IV over 2 hours every 12 hours on days 1 to 7
Daunorubicin (Cerubidine) 40 mg/m² IV bolus once per day on days 1 to 3

7-day course

Regimen variant #4, 1400/135 (CI Ara-C)

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Dillman et al. 1991 (CALGB 8321)	1982-1986	Phase 3 (E-esc)	7+3d; lower-dose Ara-C	Did not meet primary efficacy endpoints
Weick et al. 1996	1986-1991	Phase 3 (C)	HiDAC+3d	Seems to have inferior RFS
Zittoun et al. 1996 (AML 8B)	1986-1993	Phase 3 (C)	7+3d & GM-CSF	Did not meet primary efficacy endpoint
Moore et al. 2004 (CALGB 9222)	1992-1995	Non-randomized portion of phase 3 RCT
Anderson et al. 2002 (SWOG S9333)	1995-1998	Phase 3 (C)	ME	Did not meet primary endpoint of CR rate
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)	2000-2006	Phase 3 (C)	7+3d; high-dose	Inferior CR rate
Lee et al. 2011 (ADcomparison)	2001-2008	Phase 3 (C)	7+3d; high-dose	Seems to have inferior OS
Stone et al. 2015 (ACCEDE)	2008-2010	Phase 3 (C)	Amonafide & Cytarabine	Did not meet primary endpoint of CR rate

Chemotherapy

Cytarabine (Ara-C) 200 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m²)
Daunorubicin (Cerubidine) 45 mg/m² IV once per day on days 1 to 3

7-day course

Subsequent treatment

CALGB 9222: HiDAC versus multi-agent chemotherapy consolidation
HOVON 43 AML/SAKK 30/01: MiDAC consolidation
ACCEDE: patients received a second course of the same regimen if their day 14 bone marrow was positive. Patients with PR or better at time of count recovery received allogeneic stem cell transplant if eligible, otherwise HiDAC if younger than 60 or MiDAC if greater than or equal to 60.

References

Yates JW, Wallace HJ Jr, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973 Nov-Dec;57(4):485-8. PubMed
CALGB 7421: Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Bloomfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Ellison RR, Kung F, Henry P, McIntyre OR, Kaan SK. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood. 1981 Dec;58(6):1203-12. link to original article contains dosing details in manuscript PubMed
Omura GA, Vogler WR, Lefante J, Silberman H, Knospe W, Gordon D, Jarrell R. Treatment of acute myelogenous leukemia: influence of three induction regimens and maintenance with chemotherapy or BCG immunotherapy. Cancer. 1982 Apr 15;49(8):1530-6. link to original article contains dosing details in manuscript PubMed
CALGB 7721: Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosik H, Levy R, Hoagland C, Henry P, Gottlieb A, Cornell C, Berenberg J, Hutchison JL, Raich P, Nissen N, Ellison RR, Frelick R, James GW, Falkson G, Silver RT, Haurani F, Green M, Henderson E, Leone L, Holland JF. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood. 1982 Aug;60(2):454-62. link to original article contains dosing details in manuscript PubMed
Vogler WR, Winton EF, Gordon DS, Raney MR, Go B, Meyer L; SECSG. A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial. Blood. 1984 May;63(5):1039-45. link to original article PubMed
CALGB 7921: Preisler H, Davis RB, Kirshner J, Dupre E, Richards F 3rd, Hoagland HC, Kopel S, Levy RN, Carey R, Schulman P, Gottlieb AJ, McIntyre OR. Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: a Cancer and Leukemia Group B study. Blood. 1987 May;69(5):1441-9. link to original article contains dosing details in manuscript PubMed
Stein RS, Vogler WR, Winton EF, Cohen HJ, Raney MR, Bartolucci A; Southeastern Cancer Study Group. Therapy of acute myelogenous leukemia in patients over the age of 50: a randomized Southeastern Cancer Study Group trial. Leuk Res. 1990;14(10):895-903. link to original article PubMed
Bishop JF, Lowenthal RM, Joshua D, Matthews JP, Todd D, Cobcroft R, Whiteside MG, Kronenberg H, Ma D, Dodds A, Herrmann R, Szer J, Wolf MM, Young G; Australian Leukemia Study Group. Etoposide in acute nonlymphocytic leukemia. Blood. 1990 Jan 1;75(1):27-32. link to original article contains dosing details in abstract PubMed
Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. PubMed
CALGB 8321: Dillman RO, Davis RB, Green MR, Weiss RB, Gottlieb AJ, Caplan S, Kopel S, Preisler H, McIntyre OR, Schiffer C. A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B. Blood. 1991 Nov 15;78(10):2520-6. link to original article contains dosing details in manuscript PubMed
Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. link to original article contains dosing details in manuscript PubMed
Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL; Southeastern Cancer Study Group. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group study. J Clin Oncol. 1992 Jul;10(7):1103-11. link to original article contains dosing details in abstract PubMed
AML 8B: Zittoun R, Suciu S, Mandelli F, de Witte T, Thaler J, Stryckmans P, Hayat M, Peetermans M, Cadiou M, Solbu G, Petti MC, Willemze R. Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol. 1996 Jul;14(7):2150-9. link to original article contains dosing details in manuscript PubMed NCT01324063
1. Update: Hengeveld M, Suciu S, Karrasch M, Specchia G, Marie JP, Muus P, Petti MC, Rotoli B, Amadori S, Fioritoni G, Leoni P, Morra E, Thaler J, Resegotti L, Fazi P, Vignetti M, Mandelli F, Zittoun R, de Witte T; EORTC; GIMEMA. Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organisation for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. Ann Hematol. 2012 Jun;91(6):825-35. Epub 2012 Mar 31. link to original article link to PMC article contains dosing details in abstract PubMed
Masaoka T, Ogawa M, Yamada K, Kimura K, Ohashi Y. A phase II comparative study of idarubicin plus cytarabine versus daunorubicin plus cytarabine in adult acute myeloid leukemia. Semin Hematol. 1996 Oct;33(4 Suppl 3):12-7. contains dosing details in abstract PubMed
Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M; SWOG. A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1996 Oct 15;88(8):2841-51. link to original article contains dosing details in abstract PubMed
SWOG S9333: Anderson JE, Kopecky KJ, Willman CL, Head D, O'Donnell MR, Luthardt FW, Norwood TH, Chen IM, Balcerzak SP, Johnson DB, Appelbaum FR. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood. 2002 Dec 1;100(12):3869-76. Epub 2002 Aug 1. link to original article contains dosing details in abstract PubMed
ECOG E3993: Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. link to original article contains dosing details in manuscript PubMed NCT04446052
CALGB 9222: Moore JO, George SL, Dodge RK, Amrein PC, Powell BL, Kolitz JE, Baer MR, Davey FR, Bloomfield CD, Larson RA, Schiffer CA. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222. Blood. 2005 May 1;105(9):3420-7. Epub 2004 Nov 30. link to original article link to PMC article contains dosing details in manuscript PubMed
GIMEMA GSI 103 AMLE: Latagliata R, Breccia M, Fazi P, Iacobelli S, Martinelli G, Di Raimondo F, Sborgia M, Fabbiano F, Pirrotta MT, Zaccaria A, Amadori S, Caramatti C, Falzetti F, Candoni A, Mattei D, Morselli M, Alimena G, Vignetti M, Baccarani M, Mandelli F. Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia. Br J Haematol. 2008 Dec;143(5):681-9. Epub 2008 Oct 20. link to original article contains dosing details in manuscript PubMed
HOVON 43 AML/SAKK 30/01: Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology; AMLSG; Swiss Group for Clinical Cancer Research. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. link to original article contains dosing details in manuscript PubMed ISRCTN77039377
ECOG E1900: Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00049517
1. Update: Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016 Mar 24;127(12):1551-8. Epub 2016 Jan 11. link to original article link to PMC article PubMed
ECOG E3999: Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Luger S, Tallman MS. Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999. Blood. 2010 Nov 18;116(20):4077-85. Epub 2010 Aug 17. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00046930
ADcomparison: Lee JH, Joo YD, Kim H, Bae SH, Kim MK, Zang DY, Lee JL, Lee GW, Lee JH, Park JH, Kim DY, Lee WS, Ryoo HM, Hyun MS, Kim HJ, Min YJ, Jang YE, Lee KH; Cooperative Study Group A for Hematology. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood. 2011 Oct 6;118(14):3832-41. Epub 2011 Aug 9. link to original article contains dosing details in abstract PubMed NCT00474006
ACCEDE: Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00715637
AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01074047
1. Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed

7+3d (intermediate-dose)

7+3d: 7 days of cytarabine + 3 days of daunorubicin

Regimen variant #1, CI Ara-C (100 mg/m²)

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Büchner et al. 2012 (OSHO 061)	2002-2008	Phase 3 (C)	See paper for details	Did not meet primary endpoint of EFS
Schaich et al. 2013 (AML2003)	2003-2009	Non-randomized portion of phase 3 RCT
Walker et al. 2021 (CALGB 10201)	2004-2006	Phase 3 (C)	7+3d & Oblimersen	Did not meet primary endpoint of OS
Petersdorf et al. 2013 (SWOG S0106)	2004-2009	Phase 3 (C)	7+3d & GO	Did not meet primary endpoint of CR rate
Serve et al. 2013 (AML2006)	2006-2008	Randomized Phase 2 (C)	7+3d & Sorafenib	Did not meet primary endpoint of EFS
Röllig et al. 2015 (SORAML)	2009-2011	Randomized Phase 2 (C)	7+3d & Sorafenib	Seems to have inferior EFS
Müller-Tidow et al. 2015 (AML-AZA)	2010-2012	Phase 3 (C)	7+3d & Azacitidine	Did not meet primary endpoint of EFS
Dombret et al. 2015 (AZA-AML-001)	2010-2014	Phase 3 (C)	Azacitidine	Might have inferior OS
Lancet et al. 2018 (CLTR0310-301)	2012-2014	Phase 3 (C)	CPX-351	Inferior OS

Note: this was the upper bound of the allowable daunorubicin dose in AZA-AML-001.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 60 mg/m² IV once per day on days 1 to 3
- Note: Dombret et al. 2015 did not specify which days the daunorubicin is administered; some protocols give daunorubicin on days 3 to 5

7-day course

Subsequent treatment

AML2003: HiDAC versus MAC/MAMAC/MAC consolidation
CALGB 10201: IDAC consolidation x 2
SWOG S0106: HiDAC consolidation x 3
CLTR0310-301: 5+2d consolidation

Regimen variant #2, CI Ara-C (200 mg/m²)

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Holowiecki et al. 2004 (PALG AML1/1999)	1999-2002	Phase 3 (C)	DAC	Inferior CR rate after first induction
Chevallier et al. 2010 (LAM-2001)	2001-2005	Phase 3 (C)	7+5i	Did not meet primary endpoint of LFS
Holowiecki et al. 2012 (PALG AML1/2004)	2004-2008	Phase 3 (C)	1. DAC	Inferior OS
Holowiecki et al. 2012 (PALG AML1/2004)	2004-2008	Phase 3 (C)	2. DAF	Seems to have inferior OS
Castaigne et al. 2012 (ALFA-0701)	2008-2010	Phase 3 (C)	7+3d & GO	Inferior EFS

Chemotherapy

Cytarabine (Ara-C) 200 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m²)
Daunorubicin (Cerubidine) 60 mg/m² IV over 5 minutes once per day on days 1 to 3

Supportive therapy

"According to commonly accepted guidelines with no prophylactic IV antibiotics"
Granulocyte colony-stimulating factor recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression

7-day course

Subsequent treatment

Patients with only partial remission in both PALG studies underwent a second course with the same drugs, doses, and schedule.
PALG AML1/1999, non-responders: CLAG salvage
Patients in remission in both PALG studies: HAM, then HiDAC consolidation
ALFA-0701, CR or CRp: Cytarabine & daunorubicin consolidation

References

PALG AML1/1999: Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. link to original article contains dosing details in manuscript PubMed
LAM-2001: Chevallier P, Fornecker L, Lioure B, Béné MC, Pigneux A, Recher C, Witz B, Fegueux N, Bulabois CE, Daliphard S, Bouscary D, Vey N, Delain M, Bay JO, Turlure P, Bernard M, Himberlin C, Luquet I, Ifrah N, Harousseau JL; GOELAMS. Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial. Leukemia. 2010 Jul;24(7):1380-5. Epub 2010 May 27. link to original article contains dosing details in abstract PubMed
1. Update: Récher C, Béné MC, Lioure B, Pigneux A, Vey N, Delaunay J, Luquet I, Hunault M, Guyotat D, Bouscary D, Fegueux N, Jourdan E, Lissandre S, Escoffre-Barbe M, Bonmati C, Randriamalala E, Guièze R, Ojeda-Uribe M, Dreyfus F, Harousseau JL, Cahn JY, Ifrah N, Guardiola P; Groupe Ouest-Est d’ étude des Leucé mies Aiguës et autres. Long-term results of a randomized phase 3 trial comparing idarubicin and daunorubicin in younger patients with acute myeloid leukaemia. Leukemia. 2014 Feb;28(2):440-3. Epub 2013 Oct 9. link to original article PubMed
PALG AML1/2004: Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains dosing details in manuscript PubMed
ALFA-0701: Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. Epub 2012 Apr 5. link to original article contains dosing details in manuscript PubMed NCT00927498
1. Update: Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. link to original article link to PMC article PubMed
OSHO 061: Büchner T, Schlenk RF, Schaich M, Döhner K, Krahl R, Krauter J, Heil G, Krug U, Sauerland MC, Heinecke A, Späth D, Kramer M, Scholl S, Berdel WE, Hiddemann W, Hoelzer D, Hehlmann R, Hasford J, Hoffmann VS, Döhner H, Ehninger G, Ganser A, Niederwieser DW, Pfirrmann M. Acute Myeloid Leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML Intergroup. J Clin Oncol. 2012 Oct 10;30(29):3604-10. Epub 2012 Sep 10. link to original article contains dosing details in manuscript PubMed NCT01414231
AML2003: Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. Epub 2013 Apr 29. link to original article contains dosing details in manuscript PubMed NCT00180102
AML2006: Serve H, Krug U, Wagner R, Sauerland MC, Heinecke A, Brunnberg U, Schaich M, Ottmann O, Duyster J, Wandt H, Fischer T, Giagounidis A, Neubauer A, Reichle A, Aulitzky W, Noppeney R, Blau I, Kunzmann V, Stuhlmann R, Krämer A, Kreuzer KA, Brandts C, Steffen B, Thiede C, Müller-Tidow C, Ehninger G, Berdel WE. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. J Clin Oncol. 2013 Sep 1;31(25):3110-8. Epub 2013 Jul 29. link to original article contains dosing details in abstract PubMed NCT00373373
SWOG S0106: Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. link to original article link to PMC article PubMed NCT00085709
AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01074047
1. Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
AML-AZA: Müller-Tidow C, Tschanter P, Röllig C, Thiede C, Koschmieder A, Stelljes M, Koschmieder S, Dugas M, Gerss J, Butterfaß-Bahloul T, Wagner R, Eveslage M, Thiem U, Krause SW, Kaiser U, Kunzmann V, Steffen B, Noppeney R, Herr W, Baldus CD, Schmitz N, Götze K, Reichle A, Kaufmann M, Neubauer A, Schäfer-Eckart K, Hänel M, Peceny R, Frickhofen N, Kiehl M, Giagounidis A, Görner M, Repp R, Link H, Kiani A, Naumann R, Brümmendorf TH, Serve H, Ehninger G, Berdel WE, Krug U; Study Alliance Leukemia Group. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia. Leukemia. 2016 Mar;30(3):555-61. Epub 2015 Nov 2. link to original article contains dosing details in manuscript PubMed NCT00915252
SORAML: Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. link to original article PubMed NCT00893373
CLTR0310-301: Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. link to original article contains dosing details in abstract link to PMC article PubMed NCT01696084
1. Update: Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. link to original article PubMed
CALGB 10201: Walker AR, Marcucci G, Yin J, Blum W, Stock W, Kohlschmidt J, Mrózek K, Carroll AJ, Eisfeld AK, Wang ES, Jacobson S, Kolitz JE, Thakuri M, Sutamtewagul G, Vij R, Stuart RK, Byrd JC, Bloomfield CD, Stone RM, Larson RA. Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance). Blood Adv. 2021 Jul 13;5(13):2775-2787. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00085124.
AMLSG31-19: NCT04628026
ECOG E2906: NCT02085408
ENHANCE-2: NCT04778397

7+3d (high-dose)

7+3d: 7 days of cytarabine + 3 days of daunorubicin

Regimen variant #1, 700/270

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Fernandez et al. 2009 (ECOG E1900)	2002-2008	Phase 3 (E-esc)	7+3d; standard-dose	Superior OS Median OS: 23.7 vs 15.7 mo (HR 0.74, 95% CI 0.60-0.90)
Zeidner et al. 2015 (JHOC-J1101)	2011-2013	Randomized Phase 2 (C)	FLAM	Inferior CR rate

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 90 mg/m² IV once per day on days 1 to 3

7-day course

Subsequent treatment

JHOC-J1101: Patients with residual leukemia at day 14 underwent 5+2d salvage

Regimen variant #2, 1400/240

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Castaigne et al. 2004 (ALFA 9000)	1990-1996	Phase 3 (C)	1. 7+3d x 2 2. Timed sequential induction	Did not meet primary endpoint of RFI

Chemotherapy

Cytarabine (Ara-C) 200 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m²)
Daunorubicin (Cerubidine) 80 mg/m² IV once per day on days 1 to 3

7-day course

Regimen variant #3, 1400/270

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)	2000-2006	Phase 3 (E-esc)	7+3d; standard-dose	Superior CR rate
Lee et al. 2011 (ADcomparison)	2001-2008	Phase 3 (E-esc)	7+3d; standard-dose	Seems to have superior OS OS60: 46.8% vs 34.6% (HR 0.74, 95% CI 0.58-0.97)
Lee et al. 2017 (COSAH C-022)	2010-2014	Phase 3 (C)	7+3i	Inconclusive whether non-inferior CR rate

Chemotherapy

Cytarabine (Ara-C) 200 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m²)
Daunorubicin (Cerubidine) 90 mg/m² IV once per day on days 1 to 3

7-day course

Subsequent treatment

HOVON 43 AML/SAKK 30/01: MiDAC consolidation
COSAH C-022, with CR, good- or intermediate-risk cytogenetics: HiDAC consolidation
COSAH C-022, with CR, high-risk cytogenetics: Cytarabine & etoposide consolidation

References

ALFA 9000: Castaigne S, Chevret S, Archimbaud E, Fenaux P, Bordessoule D, Tilly H, de Revel T, Simon M, Dupriez B, Renoux M, Janvier M, Micléa JM, Thomas X, Bastard C, Preudhomme C, Bauters F, Degos L, Dombret H. Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood. 2004 Oct 15;104(8):2467-74. Epub 2004 May 13. link to original article contains dosing details in manuscript PubMed
HOVON 43 AML/SAKK 30/01: Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. link to original article contains dosing details in manuscript PubMed ISRCTN77039377
ECOG E1900: Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00049517
1. Update: Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016 Mar 24;127(12):1551-8. Epub 2016 Jan 11. link to original article link to PMC article PubMed
ADcomparison: Lee JH, Joo YD, Kim H, Bae SH, Kim MK, Zang DY, Lee JL, Lee GW, Lee JH, Park JH, Kim DY, Lee WS, Ryoo HM, Hyun MS, Kim HJ, Min YJ, Jang YE, Lee KH; Cooperative Study Group A for Hematology. A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood. 2011 Oct 6;118(14):3832-41. Epub 2011 Aug 9. link to original article contains dosing details in abstract PubMed NCT00474006
JHOC-J1101: Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01349972
COSAH C-022: Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. link to original article contains dosing details in manuscript PubMed NCT01145846

7+3d & GO

7+3d & GO: 7 days of Cytarabine, 3 days of daunorubicin, Gemtuzumab Ozogamicin

Regimen variant #1, split GO dosing

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Castaigne et al. 2012 (ALFA-0701)	2008-2010	Phase 3 (E-RT-esc)	7+3d; intermediate-dose	Seems to have superior OS OS24: 53.2% vs 41.9% (HR 0.69, 95% CI 0.49-0.98)

Chemotherapy

Cytarabine (Ara-C) 200 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m²)
Daunorubicin (Cerubidine) 60 mg/m² IV once per day on days 1 to 3

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² (maximum dose of 5 mg) IV over 2 hours once per day on days 1, 4, 7

7-day course

Subsequent treatment

Patients in CR or CRp and platelet count at least 100 x 10⁹ by day 45 after the initiation of chemotherapy: Cytarabine, Daunorubicin, Gemtuzumab ozogamicin consolidation
Patients in CR or CRp and platelet count less than 100 x 10⁹ by day 45 after the initiation of chemotherapy: Cytarabine & Daunorubicin consolidation

Regimen variant #2, single-day GO

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Petersdorf et al. 2013 (SWOG S0106)	2004-2009	Phase 3 (E-esc)	7+3d; intermediate-dose	Did not meet primary endpoint of CR rate

Note: this was a failed confirmatory study which led to the withdrawal of the FDA indication in 2010. The FDA indication was later reinstated in 2017.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 45 mg/m² IV once per day on days 1 to 3

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 6 mg/m² IV over 2 hours once on day 4

7-day course

Subsequent treatment

HiDAC consolidation x 3

References

ALFA-0701: Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. link to original article contains dosing details in manuscript PubMed NCT00927498
1. Update: Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. link to original article link to PMC article PubMed
SWOG S0106: Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00085709

7+3i

7+3i: 7 days of cytarabine + 3 days of idarubicin
AI: Ara-C (Cytarabine) & Idarubicin
IA: Idarubicin & Ara-C (Cytarabine)

Regimen variant #1, 80/12, intermittent Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Masaoka et al. 1996	NR in abstract	Randomized Phase 2 (E-switch-ic)	7+3d; standard-dose	Seems to have superior CR rate

Chemotherapy

Cytarabine (Ara-C) 80 mg/m² IV over 2 hours every 12 hours on days 1 to 7
Idarubicin (Idamycin) 12 mg/m² IV bolus once per day on days 1 to 3

7-day course

Regimen variant #2, 100/12, CI Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Mandelli et al. 1991	1984-1987	Phase 3 (E-RT-switch-ic)	7+3d	Did not meet primary endpoint of FFS
Vogler et al. 1992	1985-1989	Phase 3 (E-RT-switch-ic)	7+3d	Seems to have superior CR rate
Haas et al. 1993	1989-NR	Non-randomized
Rowe et al. 2004 (ECOG E3993)	1993-1997	Phase 3 (E-switch-ic)	1. 7+3d; standard-dose 2. 7+3d + GM-CSF 3. 7+3i + GM-CSF 4. 7+3m 5. 7+3m + GM-CSF	Did not meet primary endpoint of CR rate
Ohtake et al. 2010 (JALSG AML95)	1995-1997	Phase 3 (C)	Individualized chemotherapy	Did not meet efficacy endpoints
Miyawaki et al. 2005 (JALSG AML97)	1997-2001	Non-randomized portion of RCT
Ohtake et al. 2010 (JALSG AML201)	2001-2005	Phase 3 (C)	7+5d	Inconclusive whether non-inferior CR rate

Note: Patients in ECOG E3993 with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Idarubicin (Idamycin) 12 mg/m² IV once per day on days 1 to 3

7-day course (see note)

Regimen variant #3, 100/13, CI Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Wiernik et al. 1992	1985-1989	Phase 3 (E-RT-switch-ic)	7+3d; standard-dose	Seems to have superior OS

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Idarubicin (Idamycin) 13 mg/m² IV once per day on days 1 to 3

7-day course

Regimen variant #4, 200/12, CI Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Löwenberg et al. 2003 (HOVON/SAKK AML 29)	1995-1999	Phase 3 (C)	7+3i & G-CSF	Seems to have inferior DFS
Pautas et al. 2010 (ALFA-9801)	1999-2006	Phase 3 (C)	1. 7+3d; high-dose 2. 7+4i	Did not meet primary endpoint of EFS
Löwenberg et al. 2011 (HOVON/SAKK AML 42)	2001-2006	Phase 3 (C)	HiDAC+3i	Did not meet primary endpoint of EFS
Löwenberg et al. 2017 (HOVON-102)	2010-2013	Phase 3 (C)	7+3i & Clofarabine	Did not meet primary endpoint of EFS
Lee et al. 2017 (COSAH C-022)	2010-2014	Phase 3 (C)	7+3d; high-dose	Inconclusive whether non-inferior CR rate
Löwenberg et al. 2021 (HOVON/SAKK-132)	2015-2017	Phase 3 (C)	7+3i & Lenalidomide	Did not meet primary endpoint of EFS

Chemotherapy

Cytarabine (Ara-C) 200 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m²)
Idarubicin (Idamycin) 12 mg/m² IV over 3 hours once per day on days 1 to 3
- Note: in HOVON/SAKK AML 29 & AML 42, idarubicin was given on days 5 to 7

7-day course

Subsequent treatment

HOVON/SAKK AML 29 & AML 42: Amsacrine & Cytarabine
ALFA-9801, patients achieiving CR: cytarabine & idarubicin consolidation
COSAH C-022, patients achieving CR, good- or intermediate-risk cytogenetics: HiDAC consolidation
COSAH C-022, patients achieving CR, high-risk cytogenetics: CYVE consolidation
HOVON/SAKK-132: Daunorubicin & IDAC (remission induction cycle II)

Regimen variant #5, with range

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Dombret et al. 2015 (AZA-AML-001)	2010-2014	Phase 3 (C)	Azacitidine	Might have inferior OS

Chemotherapy

Cytarabine (Ara-C) 100 to 200 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 to 1400 mg/m²)
Idarubicin (Idamycin) 9 to 12 mg/m² IV once per day on days 1 to 3

7-day course

References

Mandelli F, Petti MC, Ardia A, Di Pietro N, Di Raimondo F, Ganzina F, Falconi E, Geraci E, Ladogana S, Latagliata R, Malleo C, Nobile F, Petti N, Rotoli B, Specchia G, Tabilio A, Resegotti L; GIMEMA. A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia: a multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer. 1991;27(6):750-5. link to original article PubMed
Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. link to original article contains dosing details in manuscript PubMed
Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PL; Southeastern Cancer Study Group. A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group study. J Clin Oncol. 1992 Jul;10(7):1103-11. link to original article contains dosing details in abstract PubMed
Haas R, Ho AD, Del Valle F, Fischer JT, Ehrhardt R, Döhner H, Witt B, Huberts H, Kaplan E, Hunstein W. Idarubicin/cytosine arabinoside and mitoxantrone/etoposide for the treatment of de novo acute myelogenous leukemia. Semin Oncol. 1993 Dec;20(6 Suppl 8):20-6. PubMed
Masaoka T, Ogawa M, Yamada K, Kimura K, Ohashi Y. A phase II comparative study of idarubicin plus cytarabine versus daunorubicin plus cytarabine in adult acute myeloid leukemia. Semin Hematol. 1996 Oct;33(4 Suppl 3):12-7. contains dosing details in abstract PubMed
HOVON/SAKK AML 29: Löwenberg B, van Putten W, Theobald M, Gmür J, Verdonck L, Sonneveld P, Fey M, Schouten H, de Greef G, Ferrant A, Kovacsovics T, Gratwohl A, Daenen S, Huijgens P, Boogaerts M; Dutch-Belgian Hemato-Oncology Cooperative Group; Swiss Group for Clinical Cancer Research. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med. 2003 Aug 21;349(8):743-52. link to original article contains dosing details in manuscript PubMed
ECOG E3993: Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. link to original article contains dosing details in manuscript PubMed NCT04446052
JALSG AML97: Miyawaki S, Sakamaki H, Ohtake S, Emi N, Yagasaki F, Mitani K, Matsuda S, Kishimoto Y, Miyazaki Y, Asou N, Matsushima T, Takahashi M, Ogawa Y, Honda S, Ohno R; Japan Adult Leukemia Study Group. A randomized, postremission comparison of four courses of standard-dose consolidation therapy without maintenance therapy versus three courses of standard-dose consolidation with maintenance therapy in adults with acute myeloid leukemia: the Japan Adult Leukemia Study Group AML 97 study. Cancer. 2005 Dec 15;104(12):2726-34. link to original article contains dosing details in abstract PubMed
ALFA-9801: Pautas C, Merabet F, Thomas X, Raffoux E, Gardin C, Corm S, Bourhis JH, Reman O, Turlure P, Contentin N, de Revel T, Rousselot P, Preudhomme C, Bordessoule D, Fenaux P, Terré C, Michallet M, Dombret H, Chevret S, Castaigne S. Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to 70 years: results of the ALFA-9801 study. J Clin Oncol. 2010 Feb 10;28(5):808-14. Epub 2010 Jan 4. link to original article contains dosing details in manuscript PubMed NCT00931138
JALSG AML95: Ohtake S, Miyawaki S, Kiyoi H, Miyazaki Y, Okumura H, Matsuda S, Nagai T, Kishimoto Y, Okada M, Takahashi M, Handa H, Takeuchi J, Kageyama S, Asou N, Yagasaki F, Maeda Y, Ohnishi K, Naoe T, Ohno R. Randomized trial of response-oriented individualized versus fixed-schedule induction chemotherapy with idarubicin and cytarabine in adult acute myeloid leukemia: the JALSG AML95 study. Int J Hematol. 2010 Mar;91(2):276-83. link to original article contains dosing details in abstract PubMed
JALSG AML201: Ohtake S, Miyawaki S, Fujita H, Kiyoi H, Shinagawa K, Usui N, Okumura H, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2358-65. Epub 2010 Aug 6. link to original article PubMed C000000157
HOVON/SAKK AML 42: Löwenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Biemond BJ, Gratwohl A, de Greef GE, Verdonck LF, Schaafsma MR, Gregor M, Theobald M, Schanz U, Maertens J, Ossenkoppele GJ; HOVON; SAKK. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011 Mar 17;364(11):1027-36. link to original article contains dosing details in manuscript PubMed NTR230
AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article contains dosing details in abstract link to PMC article PubMed NCT01074047
1. Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
HOVON-102: Löwenberg B, Pabst T, Maertens J, van Norden Y, Biemond BJ, Schouten HC, Spertini O, Vellenga E, Graux C, Havelange V, de Greef GE, de Weerdt O, Legdeur MJ, Kuball J, Kooy MV, Gjertsen BT, Jongen-Lavrencic M, van de Loosdrecht AA, van Lammeren-Venema D, Hodossy B, Breems DA, Chalandon Y, Passweg J, Valk PJ, Manz MG, Ossenkoppele GJ; HOVON; SAKK. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML. Blood. 2017 Mar 23;129(12):1636-1645. Epub 2017 Jan 3. link to original article contains dosing details in manuscript PubMed NTR2187
COSAH C-022: Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. link to original article contains dosing details in manuscript PubMed NCT01145846
HOVON/SAKK-132: Löwenberg B, Pabst T, Maertens J, Gradowska P, Biemond BJ, Spertini O, Vellenga E, Griskevicius L, Tick LW, Jongen-Lavrencic M, van Marwijk Kooy M, Vekemans MC, van der Velden WJFM, Beverloo B, Michaux L, Graux C, Deeren D, de Weerdt O, van Esser JWJ, Bargetzi M, Klein SK, Gadisseur A, Westerweel PE, Veelken H, Gregor M, Silzle T, van Lammeren-Venema D, Moors I, Breems DA, Hoogendoorn M, Legdeur MJC, Fischer T, Kuball J, Cornelissen J, Porkka K, Juliusson G, Meyer P, Höglund M, Gjertsen BT, Janssen JJWM, Huls G, Passweg J, Cloos J, Valk PJM, van Elssen CHMJ, Manz MG, Floisand Y, Ossenkoppele GJ. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood Adv. 2021 Feb 23;5(4):1110-1121. link to original article contains dosing details in manuscript link to PMC article PubMed
SWOG S1203: NCT01802333

7+3i & Sorafenib

Regimen

Study	Years of enrollment	Evidence
Ravandi et al. 2010 (BAY43-9006)	2007-2009	Phase 1/2

Note: Regimen details are from the phase 2 part of the published phase 1/2 trial.

Chemotherapy

Cytarabine (Ara-C) by the following age-based criteria:
- 60 and younger: 1500 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose: 6000 mg/m²)
- Older than 60: 1500 mg/m²/day IV continuous infusion over 72 hours, started on day 1 (total dose: 4500 mg/m²)
Idarubicin (Idamycin) 12 mg/m² IV over 60 minutes once per day on days 1 to 3

Targeted therapy

Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 7

7-day course

Subsequent treatment

Cytarabine, idarubicin, sorafenib consolidation

References

BAY43-9006: Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00542971
1. Update: Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. link to original article link to PMC article PubMed

7+3d & Glasdegib

Regimen

Study	Years of enrollment	Evidence
Cortes et al. 2018 (B1371003)	2012-NR	Phase 2

Note: glasdegib is continued beyond induction; see paper for details.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 60 mg/m² IV once per day on days 1 to 3

Targeted therapy

Glasdegib (Daurismo) 100 mg PO once per day, started on day -3

28-day course

Subsequent treatment

IDAC consolidation

References

B1371003: Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. Epub 2018 Sep 9. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01546038

7+3m

7+3m: 7 days of cytarabine + 3 days of mitoxantrone
MAC: Mitoxantrone & Ara-C (Cytarabine)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Arlin et al. 1990	NR in abstract	Phase 3 (E-RT-switch-ic)	7+3d	Did not meet efficacy endpoints
Rowe et al. 2004 (ECOG E3993)	1993-1997	Phase 3 (E-switch-ic)	1. 7+3d; standard-dose 2. 7+3d + GM-CSF 3. 7+3i 4. 7+3i + GM-CSF 5. 7+3m + GM-CSF	Did not meet primary endpoint of CR rate

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Mitoxantrone (Novantrone) 12 mg/m² IV once per day on days 1 to 3

7-day course

Subsequent treatment

Patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of 7+3m

References

Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. PubMed
ECOG E3993: Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. link to original article contains dosing details in manuscript PubMed NCT04446052

ADE (standard-dose Ara-C)

ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide
7-3-7: 7 days of Cytarabine, 3 days of Daunorubicin, 7 days of Etoposide
8-3-5: 8 days of Cytarabine, 3 days of Daunorubicin, 5 days of Etoposide
10-3-5: 10 days of Cytarabine, 3 days of Daunorubicin, 5 days of Etoposide

Regimen variant #1, 7-3-7, 700/150/525

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bishop et al. 1996	1987-1991	Phase 3 (C)	ADE (high-dose Ara-C)	Inferior DFS

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1 to 3
Etoposide (Vepesid) 75 mg/m² IV once per day on days 1 to 7

7-day course; can be repeated up to 3 times if CR not achieved

Subsequent treatment

5-2-5 consolidation x 2

Regimen variant #2, 7-3-3, 700/180/300

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Baer et al. 2002 (CALGB 9720)	1998-1999	Phase 3 (C)	ADEP	Did not meet primary endpoint of CR rate

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 60 mg/m² IV once per day on days 1 to 3
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3

7-day course

Regimen variant #3, 7-3-3, 700/270/300

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kolitz et al. 2010 (CALGB 19808)	2001-2003	Phase 3 (C)	ADEP	Did not meet primary endpoints of DFS/OS

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Daunorubicin (Cerubidine) 90 mg/m² IV once per day on days 1 to 3
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3

7-day course

Regimen variant #4, 10-3-5, 1000/150/250, CI Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Willemze et al. 2013 (EORTC-GIMEMA AML-12)	1999-2008	Phase 3 (C)	ADE (high-dose Ara-C)	Seems to have inferior OS

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 10 days, started on day 1 (total dose: 1000 mg/m²)
Daunorubicin (Cerubidine) 50 mg/m² IV over 5 minutes once per day on days 1, 3, 5
Etoposide (Vepesid) 50 mg/m² IV over 60 minutes once per day on days 1 to 5

10-day course

Regimen variant #5, 10-3-5, 1025/150/500, CI Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Mandelli et al. 2009 (EORTC-GIMEMA AML-10)	1993-1999	Phase 3 (C)	1. AIE 2. AME	Did not meet primary endpoint of OS

Chemotherapy

Cytarabine (Ara-C) 25 mg/m²/day IV bolus once on day 1, then 100 mg/m²/day IV continuous infusion over 10 days (total dose: 1025 mg/m²)
Daunorubicin (Cerubidine) 50 mg/m² IV over 5 minutes once per day on days 1, 3, 5
Etoposide (Vepesid) 100 mg/m² IV over 60 minutes once per day on days 1 to 5

10-day course

Regimen variant #6, 8-3-5, 1600/150/500, intermittent Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hann et al. 1997 (UK MRC AML10)	1988-1995	Phase 3 (E-switch-ic)	DAT 3+8	Did not meet efficacy endpoints
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase 3 (C)	See link	See link

Note: these trials have complicated treatment schemas; see papers for details.

Preceding treatment

UK MRC AML10: ADE 10-3-5 induction

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV every 12 hours on days 1 to 8
Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 5

8-day course

Subsequent treatment

UK MRC AML10: MACE consolidation
UK MRC AML15: Consolidation (see paper for details)

Regimen variant #7, 10-3-5, 2000/150/500, intermittent Ara-C

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hann et al. 1997 (UK MRC AML10)	1988-1995	Phase 3 (E-switch-ic)	DAT 3+10	Did not meet efficacy endpoints
Burnett et al. 1999 (UK MRC AML12)	1993-1997	Phase 3 (C)	See link	See link
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase 3 (C)	See link	See link

Note: these trials have complicated treatment schemas; see papers for details.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV every 12 hours on days 1 to 10
Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5
Etoposide (Vepesid) 100 mg/m² IV over 60 minutes once per day on days 1 to 5

10-day course

Subsequent treatment

ADE 8-3-5 re-induction

References

Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. link to original article contains dosing details in abstract PubMed
UK MRC AML10: Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK; Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia: results of the Medical Research Council's 10th AML trial (MRC AML10). Blood. 1997 Apr 1;89(7):2311-8. link to original article contains dosing details in manuscript PubMed
1. Update: Burnett AK, Goldstone AH, Stevens RM, Hann IM, Rees JK, Gray RG, Wheatley K; UK Medical Research Council Adult and Children's Leukaemia Working Parties. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet. 1998 Mar 7;351(9104):700-8. link to original article PubMed
UK MRC AML12: Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood. 1999 Jun 15;93(12):4131-43. link to original article PubMed NCT00002658
1. Update: Burnett AK, Hills RK, Milligan DW, Goldstone AH, Prentice AG, McMullin MF, Duncombe A, Gibson B, Wheatley K. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. J Clin Oncol. 2010 Feb 1;28(4):586-95. Epub 2009 Dec 28. link to original article PubMed
CALGB 9720: Baer MR, George SL, Dodge RK, O'Loughlin KL, Minderman H, Caligiuri MA, Anastasi J, Powell BL, Kolitz JE, Schiffer CA, Bloomfield CD, Larson RA. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002 Aug 15;100(4):1224-32. link to original article contains dosing details in abstract PubMed NCT00003190
1. Update: Baer MR, George SL, Caligiuri MA, Sanford BL, Bothun SM, Mrózek K, Kolitz JE, Powell BL, Moore JO, Stone RM, Anastasi J, Bloomfield CD, Larson RA. Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720. J Clin Oncol. 2008 Oct 20;26(30):4934-9. Epub 2008 Jun 30. link to original article link to PMC article PubMed
EORTC-GIMEMA AML-10: Mandelli F, Vignetti M, Suciu S, Stasi R, Petti MC, Meloni G, Muus P, Marmont F, Marie JP, Labar B, Thomas X, Di Raimondo F, Willemze R, Liso V, Ferrara F, Baila L, Fazi P, Zittoun R, Amadori S, de Witte T; EORTC; GIMEMA. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. J Clin Oncol. 2009 Nov 10;27(32):5397-403. Epub 2009 Oct 13. Erratum in: J Clin Oncol. 2010 Mar 10;28(8):1438. link to original article link to PMC article PubMed
1. Update: Baron F, Efficace F, Cannella L, Muus P, Trisolini S, Halkes CJM, Fazi P, Vignetti M, Marie JP, Chiusolo P, van der Velden W, La Sala E, Vitolo U, Thomas X, Lefrère F, Di Raimondo F, Bourhis JH, Specchia G, Guimarães JE, Allione B, Vrhovac R, Ferrara F, Stevens-Kroef M, Meert L, de Witte T, Willemze R, Amadori S, Suciu S. Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study. Am J Hematol. 2020 Jul;95(7):749-758. Epub 2020 Apr 17. link to original article PubMed
CALGB 19808: Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL, DeAngelo DJ, Shea TC, Stock W, Baer MR, Hars V, Maharry K, Hoke E, Vardiman JW, Bloomfield CD, Larson RA; Cancer and Leukemia Group B. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood. 2010 Sep 2;116(9):1413-21. Epub 2010 Jun 3. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00006363
UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
1. Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
2. Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed
EORTC-GIMEMA AML-12: Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. link to original article contains dosing details in manuscript PubMed NCT00004128

ADE (high-dose Ara-C)

ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide
HIDAC-3-5: HIgh-Dose Ara-C (Cytarabine), 3 days of Daunorubicin, 5 days of Etoposide
HIDAC-3-7: HIgh-Dose Ara-C (Cytarabine), 3 days of Daunorubicin, 7 days of Etoposide

Regimen variant #1, HIDAC-3-5

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Willemze et al. 2013 (EORTC-GIMEMA AML-12)	1999-2008	Phase 3 (E-esc)	ADE (standard-dose Ara-C)	Seems to have superior OS OS72: 42.5% vs 38.7% (HR 0.89, 95% CI 0.79-1.00)

Chemotherapy

Cytarabine (Ara-C) 3000 mg/m² IV over 3 hours every 12 hours on days 1, 3, 5, 7 (total dose: 24,000 mg/m²)
Daunorubicin (Cerubidine) 50 mg/m² IV over 5 minutes once per day on days 1, 3, 5
Etoposide (Vepesid) 50 mg/m² IV over 60 minutes once per day on days 1 to 5

7-day course

Regimen variant #2, HIDAC-3-7

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bishop et al. 1996	1987-1991	Phase 3 (E-esc)	ADE (standard-dose Ara-C)	Superior DFS

Chemotherapy

Cytarabine (Ara-C) 3000 mg/m² IV every 12 hours on days 1, 3, 5, 7 (total dose per cycle: 24,000 mg/m²)
Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1 to 3
Etoposide (Vepesid) 75 mg/m² IV once per day on days 1 to 7

7-day course; can be repeated up to 3 times if CR not achieved

Subsequent treatment

5-2-5 consolidation x 2

References

Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. link to original article contains dosing details in abstract PubMed
EORTC-GIMEMA AML-12: Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. link to original article contains dosing details in manuscript PubMed NCT00004128

AIE

AIE: Ara-C (Cytarabine), Idarubicin, Etoposide
ICE: Idarubicin, Cytarabine, Etoposide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bradstock et al. 2004 (ALLG M7)	1995-2000	Non-randomized portion of RCT
de Witte et al. 2010 (CRIANT)	1996-2003	Non-randomized portion of phase 3 RCT
Schlenk et al. 2004	1998-2001	Phase 3 (C)	A-ICE	Inferior OS
Russo et al. 2005	1999-2002	Phase 3 (C)	FLAI	Inferior CR rate
Bassan et al. 2019 (NILG AML 02/06)	2007-2012	Phase 3 (C)	Sequential high-dose therapy	Did not meet primary endpoint of CR rate

Chemotherapy

Cytarabine (Ara-C) 100 mg/m² IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m²)
Idarubicin (Idamycin) 12 mg/m² IV over 30 minutes once per day on days 1 to 3
Etoposide (Vepesid) 100 mg/m² IV over 60 minutes once per day on days 1 to 5

7-day course

Subsequent treatment

ALLG M7: ICE versus IcE consolidation
NILG AML 02/06, early CR: IC consolidation

References

ALLG M7: Bradstock KF, Matthews JP, Lowenthal RM, Baxter H, Catalano J, Brighton T, Gill D, Eliadis P, Joshua D, Cannell P, Schwarer AP, Durrant S, Gillett A, Koutts J, Taylor K, Bashford J, Arthur C, Enno A, Dunlop L, Szer J, Leahy M, Juneja S, Young GA; Australasian Leukaemia and Lymphoma Group. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood. 2005 Jan 15;105(2):481-8. Epub 2004 Jun 22. link to original article PubMed
Schlenk RF, Fröhling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, Grimminger W, Götze K, Waterhouse C, Schoch R, Pralle H, Mergenthaler HG, Hensel M, Koller E, Kirchen H, Preiss J, Salwender H, Biedermann HG, Kremers S, Griesinger F, Benner A, Addamo B, Döhner K, Haas R, Döhner H; AML Study Group Ulm. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004 Nov;18(11):1798-803. link to original article PubMed
Russo D, Malagola M, de Vivo A, Fiacchini M, Martinelli G, Piccaluga PP, Damiani D, Candoni A, Michielutti A, Castelli M, Testoni N, Ottaviani E, Rondoni M, Pricolo G, Mazza P, Zuffa E, Zaccaria A, Raspadori D, Bocchia M, Lauria F, Bonini A, Avanzini P, Gugliotta L, Visani G, Fanin R, Baccarani M. Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients. Br J Haematol. 2005 Oct;131(2):172-9. Erratum in: Br J Haematol. 2006 Mar;132(6):804. link to original article PubMed
CRIANT: de Witte T, Hagemeijer A, Suciu S, Belhabri A, Delforge M, Kobbe G, Selleslag D, Schouten HC, Ferrant A, Biersack H, Amadori S, Muus P, Jansen JH, Hellström-Lindberg E, Kovacsovics T, Wijermans P, Ossenkoppele G, Gratwohl A, Marie JP, Willemze R. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: final results of a prospective randomized European Intergroup Trial. Haematologica. 2010 Oct;95(10):1754-61. Epub 2010 May 21. link to original article link to PMC article PubMed NCT00002926
NILG AML 02/06: Bassan R, Intermesoli T, Masciulli A, Pavoni C, Boschini C, Gianfaldoni G, Marmont F, Cavattoni I, Mattei D, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Ciceri F, Bernardi M, Scattolin AM, Todisco E, Campiotti L, Corradini P, Cortelezzi A, Ferrero D, Zanghì P, Oldani E, Spinelli O, Audisio E, Cortelazzo S, Bosi A, Falini B, Pogliani EM, Rambaldi A. Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. Blood Adv. 2019 Apr 9;3(7):1103-1117. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00495287

CIA

CIA: Clofarabine, Idarubicin, Ara-C (Cytarabine)

Regimen variant #1, 15/10/1000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Jabbour et al. 2017 (MDACC 2010-0788)	2011-2016	Randomized Phase 2 (E-switch-ic)	FIA	Did not meet primary endpoint of EFS

Chemotherapy

Clofarabine (Clolar) 15 mg/m² IV once per day on days 1 to 5, given 4 hours before cytarabine
Idarubicin (Idamycin) 10 mg/m² IV once per day on days 1 to 3
Cytarabine (Ara-C) 1000 mg/m² IV over 2 hours once per day on days 1 to 5

5-day course

Subsequent treatment

Patients not achieving CR or CRp: Optional second CIA induction
Patients achieving CR or CRp: CIA consolidation

Regimen variant #2, 20/10/1000

Study	Years of enrollment	Evidence
Nazha et al. 2013	2010-2012	Phase 2

Chemotherapy

Clofarabine (Clolar) 20 mg/m² IV over 60 minutes once per day on days 1 to 5
Idarubicin (Idamycin) 10 mg/m² IV over 30 minutes once per day on days 1 to 3
Cytarabine (Ara-C) 1000 mg/m² IV over 2 hours once per day on days 1 to 5

Supportive therapy

Levofloxacin (Levaquin)
Itraconazole (Sporanox)
Valacyclovir (Valtrex)
Granulocyte colony-stimulating factor neither mandated nor forbidden and given per physician discretion

5-day course

Subsequent treatment

Patients with PR: a second course with the same drugs, doses, and schedule.
Patients achieving CR or CRi: CIA consolidation

References

Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. long link to original article contains dosing details in manuscript link to PMC article PubMed
MDACC 2010-0788: Jabbour E, Short NJ, Ravandi F, Huang X, Xiao L, Garcia-Manero G, Plunkett W, Gandhi V, Sasaki K, Pemmaraju N, Daver NG, Borthakur G, Jain N, Konopleva M, Estrov Z, Kadia TM, Wierda WG, DiNardo CD, Brandt M, O'Brien SM, Cortes JE, Kantarjian H. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer. 2017 Nov 15;123(22):4430-4439. Epub 2017 Jul 14. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01289457

DA 3 + 10

DA 3 + 10: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine

Regimen variant #1, 50 mg/m² dauno

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase 3 (C)	See link	See link
Burnett et al. 2012 (UK NCRI AML16)	2006-2010	Phase 3 (C)	DA 3 + 10, GO	Seems to have inferior OS

Note: this regimen is very similar to 7+3d; standard-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3. Both trials have complicated treatment schemas; see papers for details.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m² IV every 12 hours on days 1 to 10
Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5

10-day course

Subsequent treatment

See papers for details (to be completed).

Regimen variant #2, 60 mg/m² dauno

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2015 (UK NCRI AML17)	2011-2013	Phase 3 (C)	DA 3 + 10; high-dose	Did not meet primary endpoint of OS

Note: this regimen is very similar to 7+3d; intermediate-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m² IV every 12 hours on days 1 to 10
Daunorubicin (Cerubidine) 60 mg/m² IV once per day on days 1, 3, 5

10-day course

Subsequent treatment

CBF: DA 3+8 & GO
Non-CBF, no FLT3 mutation, not poor risk: DA 3+8 versus DA 3+8 & Everolimus
Poor risk other than FLT3 mutation: Clofarabine & Daunorubicin versus FLAG-Ida

References

UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
1. Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
2. Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed
UK NCRI AML16: Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed ISRCTN11036523
1. Update: Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. link to original article contains dosing details in manuscript PubMed
2. Update: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. link to original article link to PMC article PubMed
UK NCRI AML17: Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m² vs 60 mg/m² in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. link to original article contains dosing details in manuscript link to PMC article PubMed ISRCTN55675535
1. Update: Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. link to original article link to PMC article PubMed

DA 3 + 10, GO

DA 3 + 10, GO: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine, Gemtuzumab Ozogamicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase 3 (E-esc)	See link	See link
Burnett et al. 2012 (UK NCRI AML16)	2006-2010	Phase 3 (E-esc)	DA 3 + 10	Seems to have superior OS OS36: 25% vs 20% (HR 0.87, 95% CI 0.76-1.00)

Note: Both trials have complicated treatment schemas; see papers for details.

Chemotherapy

Cytarabine (Ara-C) 100 mg/m² IV every 12 hours on days 1 to 10
Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV once on day 1

10-day course

Subsequent treatment

See paper for details (to be completed).

References

UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
1. Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
2. Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed
UK NCRI AML16: Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed ISRCTN11036523
1. Update: Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. link to original article contains dosing details in manuscript PubMed
2. Update: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. link to original article link to PMC article PubMed

DAC

DAC: Daunorubicin, Ara-C (Cytarabine), Cladribine

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Holowiecki et al. 2004 (PALG AML1/1999)	1999-2002	Phase 3 (E-esc)	DA	Superior CR rate after first induction
Holowiecki et al. 2012 (PALG AML1/2004)	2004-2008	Phase 3 (E-esc)	1. DA	Superior OS Median OS: 24 vs 14 mo (HR 0.69, 97.5% CI 0.5-0.96)
Holowiecki et al. 2012 (PALG AML1/2004)	2004-2008	Phase 3 (E-esc)	2. DAF	Seems to have superior OS

Chemotherapy

Daunorubicin (Cerubidine) 60 mg/m² IV over 5 minutes once per day on days 1 to 3
Cytarabine (Ara-C) 200 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m²)
Cladribine (Leustatin) 5 mg/m² IV over 3 hours once per day on days 1 to 5

Supportive therapy

"According to commonly accepted guidelines with no prophylactic IV antibiotics"
Granulocyte colony-stimulating factor recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression

7-day course

Subsequent treatment

Patients with only partial remission in both studies underwent a second course with the same drugs, doses, and schedule.
Non-responders in PALG AML1/1999: CLAG salvage
Patients in remission in both studies: HAM, then HiDAC consolidation

References

PALG AML1/1999: Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. link to original article contains dosing details in manuscript PubMed
PALG AML1/2004: Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains dosing details in manuscript PubMed

FLAG-Ida

FLAG-Ida: FLudarabine, Ara-C (Cytarabine), G-CSF (Lenograstim), Idarubicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2010 (UK MRC AML15)	2002-2006	Phase 3 (C)	1. ADE 10+3+5 2. DA 3+10 3. DA 3+10 & GO 4. FLAG-Ida & GO	Did not meet primary endpoint of OS¹

¹While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV once per day on days 2 to 6
Cytarabine (Ara-C) 2000 mg/m² IV over 4 hours once per day on days 2 to 6, given 4 hours after fludarabine
Idarubicin (Idamycin) 8 mg/m² IV once per day on days 4 to 6

Growth factor therapy

Lenograstim (Granocyte) 263 mcg SC once per day on days 1 to 7

7-day course

Subsequent treatment

See paper for details

References

UK MRC AML15: Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed ISRCTN17161961
1. Update: Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. link to original article PubMed
2. Update: Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. link to original article PubMed

HAA

HAA: Homoharringtonine (Omacetaxine), Ara-C (Cytarabine), Aclarubicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Jin et al. 2013	2007-2011	Phase 3 (E-esc)	1. DA	Superior EFS
Jin et al. 2013	2007-2011	Phase 3 (E-esc)	2. HAD	Not reported

Note: There were significantly more deaths in this arm, despite a superior primary efficacy endpoint.

Chemotherapy

Omacetaxine (Synribo) 2 mg/m²/day (route not specified) on days 1 to 7
Cytarabine (Ara-C) 100 mg/m² IV once per day on days 1 to 7
Aclarubicin (Aclacinon) 20 mg IV once per day on days 1 to 7

7-day course

Subsequent treatment

Patient in CR: IDAC consolidation x 2

References

Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. Epub 2013 May 9. link to original article contains dosing details in abstract PubMed ChiCTR-TRC-06000054

ICL

ICL: Idarubicin, Cytarabine, Lomustine

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Pigneux et al. 2017 (LAM-SA 2007)	2008-2011	Phase 3 (E-esc)	IA	Seems to have superior OS OS24: 56% vs 48% (HR 0.73, 95% CI 0.54-0.99)

Chemotherapy

Idarubicin (Idamycin) 8 mg/m² IV once per day on days 1 to 5
Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)
Lomustine (CCNU) 200 mg/m² PO once on day 1

7-day course

Subsequent treatment

IC and methotrexate/mercaptopurine with norethandrolone

References

LAM-SA 2007: Pigneux A, Béné MC, Salmi LR, Dumas PY, Delaunay J, Bonmati C, Guièze R, Luquet I, Cornillet-Lefebvre P, Delabesse E, Ianotto JC, Ojeda-Uribe M, Hunault M, Banos A, Fornecker LM, Bernard M, Jourdan E, Vey N, Zerazhi H, Hishri Y, Mineur A, Asselineau J, Delepine R, Cahn JY, Ifrah N, Récher C; French Innovative Leukemia Organization. Improved survival by adding lomustine to conventional chemotherapy for elderly patients with aml without unfavorable cytogenetics: results of the LAM-SA 2007 FILO trial. J Clin Oncol. 2018 36:32, 3203-3210. Epub 2018 Sep 27. link to original article contains dosing details in manuscript PubMed NCT00590837

MEC

MEC: Mitoxantrone, Etoposide, Cytarabine
MICE: MItoxantrone, Cytarabine, Etoposide
MAE: Mitoxantrone, Ara-C (Cytarabine), Etoposide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Amadori et al. 2005 (EORTC/GIMEMA AML-13)	1995-2001	Phase 3 (C)	MICE & G-CSF	Inferior CR rate
Amadori et al. 2013 (EORTC/GIMEMA AML-17)	2002-2007	Phase 3 (C)	GO, then MICE	Might have superior OS Median OS: 10 vs 7.1 mo (HR 0.83, 95% CI 0.69-1.01)

Chemotherapy

Mitoxantrone (Novantrone) 7 mg/m² IV once per day on days 1, 3, 5
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m²)

7-day course

References

EORTC/GIMEMA AML-13: Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, Muus P, Lefrère F, Berneman Z, Fillet G, Denzlinger C, Willemze R, Leoni P, Leone G, Casini M, Ricciuti F, Vignetti M, Beeldens F, Mandelli F, De Witte T; EORTC; GIMEMA. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood. 2005 Jul 1;106(1):27-34. Epub 2005 Mar 10. link to original article link to PMC article PubMed NCT00002719
1. Update: Jehn U, Suciu S, Thomas X, Lefrère F, Muus P, Berneman Z, Marie JP, Adamo F, Fillet G, Nobile F, Ricciuti F, Leone G, Rizzoli V, Montanaro M, Beeldens F, Fazi P, Mandelli F, Willemze R, de Witte T, Amadori S. Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial. Leukemia. 2006 Oct;20(10):1723-30. Epub 2006 Aug 17. link to original article PubMed
EORTC/GIMEMA AML-17: Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, De Fabritiis P, Venditti A, Ho AD, Lübbert M, Thomas X, Latagliata R, Halkes CJ, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013 Dec 10;31(35):4424-30. Epub 2013 Oct 14. link to original article contains dosing details in manuscript PubMed NCT00052299

Subsequent induction therapy, standard and older "fit" patients

Note: these are aggressive remission induction regimens given with curative intent, as part of a pre-planned protocol of therapy. They are less common in adults in the United States, but are often called "Course 2" or similar in other countries. These are to be distinguished from salvage therapy, which is outline below.

DA 3+8

DA 3+8: Daunorubicin & Ara-C (Cytarabine), 3 days of daunorubicin + 10 days of cytarabine

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2015 (UK NCRI AML17)	2009-2012	Phase 3 (C)]]	DA 3+8 & Everolimus	Did not meet primary endpoint of RFS

Biomarker eligibility criteria

Non-core-binding factor (CBF) AML, no FLT3 mutation, and not poor risk

Preceding treatment

DA 3+10 versus DA 3+10; high-dose

Chemotherapy

Cytarabine (Ara-C) 100 mg/m² IV every 12 hours on days 1 to 8
Daunorubicin (Cerubidine) 60 mg/m² IV once per day on days 1, 3, 5

10-day course

Subsequent treatment

HiDAC x 1 versus HiDAC x 2

References

UK NCRI AML17: Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m² vs 60 mg/m² in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. link to original article contains dosing details in manuscript link to PMC article PubMed ISRCTN55675535
1. Update: Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. link to original article link to PMC article PubMed

DA 3+8 & GO

DA 3+8 & GO: Daunorubicin, Ara-C (Cytarabine), 3 days of daunorubicin + 8 days of cytarabine, Gemtuzumab Ozogamicin

Regimen

Study	Years of enrollment	Evidence
Burnett et al. 2015 (UK NCRI AML17)	2011-2013	Non-randomized portion of phase 3 RCT

Biomarker eligibility criteria

Core-binding factor (CBF) AML

Preceding treatment

DA 3+10 versus DA 3+10; high-dose

Chemotherapy

Cytarabine (Ara-C) 100 mg/m² IV every 12 hours on days 1 to 8
Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV once on day 1

8-day course

Subsequent treatment

HiDAC x 1 versus HiDAC x 2

References

UK NCRI AML17: Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m² vs 60 mg/m² in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. link to original article contains dosing details in manuscript link to PMC article PubMed ISRCTN55675535
1. Update: Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. link to original article link to PMC article PubMed

First-line induction therapy, older or "unfit" patients

Note: these regimens are generally considered to be part of a non-curative line of treatment.

Azacitidine monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Fenaux et al. 2009 (AZA PH GL 2003)	2003-2007	Phase 3 (E-esc)	Investigator's choice of: 1. Best supportive care 2. LoDAC 3. Intensive chemotherapy	Superior OS Median OS: 24.5 vs 16 mo (HR 0.47, 95% CI 0.28-0.79)
Dombret et al. 2015 (AZA-AML-001)	2010-2014	Phase 3 (E-esc)	Investigator's choice of: 1. 7+3d; standard-dose 2. 7+3d; intermediate-dose 3. 7+3i 4. Best supportive care 5. LoDAC	Might have superior OS Median OS: 10.4 vs 6.5 mo (HR 0.85, 95% CI 0.69-1.03)
Vives et al. 2021 (FLUGAZA)	2014-NR in abstract	Phase 3 (E-switch-ooc)	FLUGA	Superior OS Median OS: 9.8 vs 4.1 mo
DiNardo et al. 2020 (VIALE-A)	2017-2019	Phase 3 (C)	Azacitidine & Venetoclax	Inferior OS

Note: Patients in AZA PH GL 2003 had 20-30% blasts in the bone marrow.

Chemotherapy

Azacitidine (Vidaza) 75 mg/m² SC once per day on days 1 to 7

28-day cycle for at least 6 cycles

References

AZA PH GL 2003: Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. Epub 2009 Dec 21. link to original article PubMed NCT00071799
AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01074047
1. Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
VIALE-A: DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. link to original article contains dosing details in abstract PubMed NCT02993523
FLUGAZA: Vives S, Martínez-Cuadrón D, Bergua Burgues J, Algarra L, Tormo M, Martínez-Sánchez MP, Serrano J, Herrera P, Ramos F, Salamero O, Lavilla E, López-Lorenzo JL, Gil C, Vidriales B, Falantes JF, Serrano A, Labrador J, Sayas MJ, Foncillas MÁ, Amador Barciela ML, Olave MT, Colorado M, Gascón A, Fernández MÁ, Simiele A, Pérez-Encinas MM, Rodríguez-Veiga R, García O, Martínez-López J, Barragán E, Paiva B, Sanz MÁ, Montesinos P; PETHEMA Group. A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia. Cancer. 2021 Jun 15;127(12):2003-2014. Epub 2021 Feb 24. link to original article PubMed NCT02319135
PEVOLAM: NCT04090736
PRAN-16-52: NCT03151408

Azacitidine & Venetoclax

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
DiNardo et al. 2018 (M14-358)	2014-2015	Phase 1b, >20 pts (RT)
DiNardo et al. 2020 (VIALE-A)	2017-2019	Phase 3 (E-RT-esc)	Azacitidine	Superior OS Median OS: 14.7 vs 9.6 mo (HR 0.66, 95% CI 0.52-0.85)

Note: Patients with WBC greater than 25 x 10⁹/L at presentation were pre-treated with hydroxyurea or leukapheresis.

Chemotherapy

Azacitidine (Vidaza) 75 mg/m² IV or SC once per day on days 1 to 7

Targeted therapy

Venetoclax (Venclexta) as follows:
- Cycle 1: 20 mg PO once on day 2, then 50 mg PO once on day 3, then 100 mg PO once on day 4, then 200 mg PO once on day 5, then 400 mg PO once per day on days 6 to 28
- Cycle 2 onwards: 400 mg PO once per day

28-day cycles

References

M14-358: DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. link to original article contains dosing details in manuscript PubMed NCT02203773
1. Update: DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. link to original article link to PMC article PubMed
VIALE-A: DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. link to original article contains dosing details in abstract PubMed NCT02993523
ENHANCE-2: NCT04778397

Azacitidine & Gemtuzumab ozogamicin

Protocol

Study	Years of enrollment	Evidence
Nand et al. 2008	NR in abstract	Phase 2
Nand et al. 2013 (SWOG S0703)	2008-NR	Phase 2

Note: Patients with WBC greater than 10 x 10⁹/L at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC greater than x 10⁹/L. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.

Supportive therapy, pre-treatment phase

Hydroxyurea (Hydrea) 1500 mg PO twice per day or in higher doses if necessary

Once WBC is less than 10 x 10⁹/L, stop Hydrea and proceed:

Chemotherapy

Azacitidine (Vidaza) 75 mg/m² IV or SC once per day on days 1 to 7

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV once on day 8

Supportive therapy

"Appropriate premedications" which were not specified, for Gemtuzumab ozogamicin (Mylotarg)

8-day course

Subsequent treatment

If D14 bone marrow with 5% or more blasts, a second induction cycle identical to the first was administered
Patients achieving CR or CRi: Azacitidine and gemtuzumab ozogamicin consolidation, within 60 days

References

Nand S, Godwin J, Smith S, Barton K, Michaelis L, Alkan S, Veerappan R, Rychlik K, Germano E, Stiff P. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Leuk Lymphoma. 2008 Nov;49(11):2141-7. link to original article contains dosing details in manuscript PubMed
SWOG S0703: Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00658814

Clofarabine monotherapy

Regimen variant #1, 20 mg/m²

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2012 (UK NCRI AML16)	2006-2010	Phase 3 (E-switch-ic)	LoDAC	Did not meet primary endpoint of OS¹

¹Reported efficacy is based on the 2013 update.

Chemotherapy

Clofarabine (Clolar) 20 mg/m² IV over 60 minutes once per day on days 1 to 5

4- to 6-week cycle for 4 cycles

Regimen variant #2, 30 mg/m²

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2010 (UWCM-001)	2003-2005	Phase 2
Faderl et al. 2008 (MDACC 2004-0183)	2004-NR	Randomized Phase 2 (E-de-esc)	Clofarabine & LoDAC	Seems to have inferior EFS
Burnett et al. 2010 (BIOV-121)	2004-2005	Phase 2

Chemotherapy

Clofarabine (Clolar) 30 mg/m² IV over 60 minutes once per day on days 1 to 5

5-day course

Subsequent treatment

A second induction was permitted for SD or better.
MDACC 2004-0183: Responders proceeded to clofarabine & cytarabine consolidation

References

MDACC 2004-0183: Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00088218
UWCM-001; BIOV-121: Burnett AK, Russell NH, Kell J, Dennis M, Milligan D, Paolini S, Yin J, Culligan D, Johnston P, Murphy J, McMullin MF, Hunter A, Das-Gupta E, Clark R, Carr R, Hills RK. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol. 2010 May 10;28(14):2389-95. Epub 2010 Apr 12. link to original article PubMed
UK NCRI AML16: Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed ISRCTN11036523
1. Update: Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. link to original article contains dosing details in manuscript PubMed
2. Update: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. link to original article link to PMC article PubMed

Clofarabine & LoDAC

Clofarabine & LoDAC: Clofarabine & Low Dose Ara-C (Cytarabine)

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Faderl et al. 2008 (MDACC 2004-0183)	2004-NR	Randomized Phase 2 (E-esc)	Clofarabine	Seems to have superior EFS

Chemotherapy

Clofarabine (Clolar) 30 mg/m² IV over 60 minutes once per day on days 1 to 5, given first
Cytarabine (Ara-C) 20 mg SC once per day on days 1 to 14, given 4 hours after clofarabine on days 1 to 5

28- to 49-day cycle for up to 2 cycles

Subsequent treatment

CRi or better: Clofarabine & LoDAC consolidation

Regimen variant #2

Study	Years of enrollment	Evidence
Faderl et al. 2010	2008-2010	Phase 2

Chemotherapy

Clofarabine (Clolar) 20 mg/m² IV once per day on days 1 to 5
Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 10

10-day course

Subsequent treatment

Patients not achieving CR: Optional identical Clofarabine & LoDAC re-induction after at least 28 days
- Patients not achieving CR after the second induction: Decitabine salvage
Patients achieving CR: Clofarabine & low-dose cytarabine alternating with decitabine consolidation

References

MDACC 2004-0183: Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00088218
Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. link to original article link to PMC article PubMed
1. Update: Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. link to original article link to PMC article PubMed

CPX-351 monotherapy

CPX-351: Liposomal Cytarabine and Daunorubicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lancet et al. 2014 (CLTR0308-204)	2008-2009	Randomized Phase 2 (E-switch-ic)	7+3d; intermediate-dose	Might have superior ORR
Lancet et al. 2018 (CLTR0310-301)	2012-2014	Phase 3 (E-RT-switch-ic)	7+3d; intermediate-dose	Superior OS¹ Median OS: 9.3 vs 6.0 mo (HR 0.70, 95% CI 0.55-0.91)

¹Reported efficacy is based on the 2021 update.

Chemotherapy

CPX-351 (Vyxeos) as follows:
- First induction: 100 units/m² IV over 90 minutes once per day on days 1, 3, 5
- Second induction (if needed): 100 units/m² IV over 90 minutes once per day on days 1 & 3

One or two courses

Subsequent treatment

CR/CRi: CPX-351 consolidation

References

CLTR0308-204: Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, Solomon SR, Kolitz JE, Cooper M, Yeager AM, Louie AC, Feldman EJ. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014 May 22;123(21):3239-46. Epub 2014 Mar 31. link to original article link to PMC article PubMed NCT00788892
CLTR0310-301: Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. link to original article contains dosing details in abstract link to PMC article PubMed NCT01696084
1. Update: Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. link to original article PubMed

Decitabine monotherapy

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Issa et al. 2014	NR	Randomized Phase 2 (C)	Decitabine & Valproate	Did not meet primary endpoint

Chemotherapy

Decitabine (Dacogen) 20 mg/m² IV over 60 minutes once per day on days 1 to 5

4- to 6-week cycles

Regimen variant #2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kantarjian et al. 2012 (DACO-016)	2006-2009	Phase 3 (E-esc)	1. LoDAC 2. Best supportive care	Might have superior OS Median OS: 7.7 vs 5 mo (HR 0.85, 95% CI 0.69-1.04)
Kantarjian et al. 2021 (SEAMLESS)	2011-2014	Phase 3 (C)	Decitabine/Sapacitabine	Did not meet primary endpoint of OS
Montesinos et al. 2020 (JNJ AML2002)	2015-2018	Phase 2/3 (C)	Decitabine & Talacotuzumab	Did not meet primary endpoints of CR/OS

Chemotherapy

Decitabine (Dacogen) 20 mg/m² IV over 60 minutes once per day on days 1 to 5

Supportive therapy

Hydroxyurea (Hydrea) (dose not specified) could be used up until cycle 1 day 15

28-day cycles

Regimen variant #3

Study	Years of enrollment	Evidence
Blum et al. 2010 (OSU 07017)	2007-NR	Phase 2
Welch et al. 2016 (Wash U 201210102)	2013-2015	Phase 2

Chemotherapy

Decitabine (Dacogen) 20 mg/m² IV over 60 minutes once per day on days 1 to 10

Supportive therapy

Hydroxyurea (Hydrea) (dose not specified) allowed during and prior to cycle 1

28-day cycles

Subsequent treatment

OSU 07017, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above
OSU 07017, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by decitabine maintenance

References

OSU 07017: Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00492401
DACO-016: Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00260832
1. Subgroup analysis: Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. link to original article PubMed
Issa JP, Garcia-Manero G, Huang X, Cortes J, Ravandi F, Jabbour E, Borthakur G, Brandt M, Pierce S, Kantarjian HM. Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer. 2015 Feb 15;121(4):556-61. Epub 2014 Oct 21. link to original article contains dosing details in manuscript link to PMC article PubMed
Wash U 201210102: Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, Wilson RK, Baty JD, Duncavage EJ, Tandon D, Lee Y, Wartman LD, Uy GL, Ghobadi A, Tomasson MH, Pusic I, Romee R, Fehniger TA, Stockerl-Goldstein KE, Vij R, Oh ST, Abboud CN, Cashen AF, Schroeder MA, Jacoby MA, Heath SE, Luber K, Janke MR, Hantel A, Khan N, Sukhanova MJ, Knoebel RW, Stock W, Graubert TA, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016 Nov 24;375(21):2023-2036. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01687400
JNJ AML-2002: Montesinos P, Roboz GJ, Bulabois CE, Subklewe M, Platzbecker U, Ofran Y, Papayannidis C, Wierzbowska A, Shin HJ, Doronin V, Deneberg S, Yeh SP, Ozcan MA, Knapper S, Cortes J, Pollyea DA, Ossenkoppele G, Giralt S, Döhner H, Heuser M, Xiu L, Singh I, Huang F, Larsen JS, Wei AH. Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study. Leukemia. 2021 Jan;35(1):62-74. Epub 2020 Mar 16. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02472145
SEAMLESS: Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. Epub 2021 Aug 23. link to original article contains dosing details in abstract PubMed NCT01303796

Decitabine & Venetoclax

Regimen variant #1, 5 days of decitabine

Study	Years of enrollment	Evidence
DiNardo et al. 2018 (M14-358)	2014-2015	Phase 1b, >20 pts (RT)

Note: Patients with WBC greater than 25 x 10⁹/L at presentation were pre-treated with hydroxyurea or leukapheresis.

Chemotherapy

Decitabine (Dacogen) 20 mg/m² IV or SC once per day on days 1 to 5

Targeted therapy

Venetoclax (Venclexta) 400, 800, or 1200 mg PO once per day

28-day cycles

Regimen variant #2, 10 days of decitabine

Study	Years of enrollment	Evidence
DiNardo et al. 2020 (DEC10-VEN)	2018-2019	Phase 2

Note: Therapy with hydroxyurea or one dose of cytarabine up to 2000 mg/m² was allowed during cycle 1.

Chemotherapy

Decitabine (Dacogen) 20 mg/m² IV or SC once per day on days 1 to 10

Targeted therapy

Venetoclax (Venclexta) as follows:
- Cycle 1: 400 mg PO once per day
- Cycle 2 onwards: 400 mg PO once per day on days 1 to 21

28-day cycles

References

M14-358: DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. link to original article contains dosing details in manuscript PubMed NCT02203773
1. Update: DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. link to original article link to PMC article PubMed
DEC10-VEN: DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020 Oct;7(10):e724-e736. Epub 2020 Sep 5. link to original article link to PMC article PubMed NCT03404193

Gemtuzumab ozogamicin monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Amadori et al. 2016 (EORTC/GIMEMA AML-19)	2004-2013	Phase 3 (E-RT-esc)	Best supportive care	Superior OS Median OS: 4.9 vs 3.6 mo (HR 0.69, 95% CI 0.53-0.90)

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 6 mg/m² IV once on day 1, then 3 mg/m² IV once on day 8

8-day course

Subsequent treatment

Patients with benefit: Gemtuzumab ozogamicin maintenance

References

EORTC/GIMEMA AML-19: Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. link to original article contains dosing details in manuscript PubMed NCT00091234

Glasdegib & LoDAC

Glasdegib & LoDAC: Glasdegib & Low Dose Ara-C (Cytarabine)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cortes et al. 2018 (BRIGHT AML 1003)	2014-NR	Randomized Phase 2 (E-RT-esc)	LoDAC	Superior OS¹ Median OS: 8.3 vs 4.3 mo (HR 0.495, 95% CI 0.325-0.75)

¹Reported efficacy is based on the 2021 update.

Chemotherapy

Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 10

Targeted therapy

Glasdegib (Daurismo) 100 mg PO once per day

28-day cycles

References

BRIGHT AML 1003: Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. link to original article link to PMC article PubMed NCT01546038
1. Update: Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. link to original article link to PMC article PubMed

Low-dose Cytarabine monotherapy (LoDAC)

LoDAC: Low Dose Ara-C (Cytarabine)
LDAC: Low-dose Ara-C (Cytarabine)

Regimen variant #1, 20 mg twice per day, indefinite duration

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kantarjian et al. 2013 (SPARK-AML1)	2009-2010	Randomized Phase 2 (C)	Barasertib & LoDAC	Seems to have inferior OCRR
Döhner et al. 2014 (BI 1230.4)	2010-2011	Randomized Phase 2 (C)	LoDAC & Volasertib	Seems to have inferior OS
Cortes et al. 2018 (BRIGHT AML 1003)	2014-NR	Randomized Phase 2 (C)	Glasdegib & LoDAC	Inferior OS

Chemotherapy

Cytarabine (Ara-C) 20 mg SC twice per day on days 1 to 10

28-day cycles

Regimen variant #2, 20 mg/m² twice per day, limited duration

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Burnett et al. 2012 (UK NCRI AML16)	2006-2010	Phase 3 (C)	Clofarabine	Did not meet primary endpoint of OS¹
Sekeres et al. 2012 (SG033-0003)	2007-2010	Randomized Phase 2 (C)	LoDAC & Lintuzumab	Did not meet primary endpoint of OS
Burnett et al. 2015	2010-2012	Randomized (C)	Sapacitabine	Might have inferior CR rate
Dombret et al. 2015 (AZA-AML-001)	2010-2014	Phase 3 (C)	Azacitidine	Might have inferior OS
Dennis et al. 2015 (UK NCRI LI-1)	2012-2013	Randomized (C)	1. LDAC & Vosaroxin	Did not meet primary endpoint of CR/CRi rate
Dennis et al. 2015 (UK NCRI LI-1)	2012-2013	Randomized (C)	2. Vosaroxin	Did not meet primary endpoint of CR/CRi rate

¹Reported efficacy for UK NCRI AML16 is based on the 2016 update.

Chemotherapy

Cytarabine (Ara-C) 20 mg/m² SC twice per day on days 1 to 10

4- to 6-week cycle for up to 4 cycles

Regimen variant #3, 20 mg/m² once per day, indefinite duration

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kantarjian et al. 2012 (DACO-016)	2006-2009	Phase 3 (C)	Decitabine	Might have inferior OS
Wei et al. 2020 (VIALE-C)	2017-2018	Phase 3 (C)	LoDAC & Venetoclax	Seems to have inferior OS¹

¹Reported efficacy for VIALE-C is based on an unplanned follow-up analysis described in the initial paper.

Chemotherapy

Cytarabine (Ara-C) 20 mg/m² SC once per day on days 1 to 10

28-day cycles

References

DACO-016: Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00260832
1. Subgroup analysis: Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. link to original article PubMed
SG033-0003: Sekeres MA, Lancet JE, Wood BL, Grove LE, Sandalic L, Sievers EL, Jurcic JG. Randomized phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia. Haematologica. 2013 Jan;98(1):119-28. Epub 2012 Jul 16. link to original article link to PMC article PubMed NCT00528333
UK NCRI AML16: Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012 Nov 10;30(32):3924-31. Epub 2012 Jul 30. link to original article contains dosing details in manuscript PubMed ISRCTN11036523
1. Update: Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. link to original article contains dosing details in manuscript PubMed
2. Update: Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. link to original article link to PMC article PubMed
SPARK-AML1: Kantarjian HM, Martinelli G, Jabbour EJ, Quintás-Cardama A, Ando K, Bay JO, Wei A, Gröpper S, Papayannidis C, Owen K, Pike L, Schmitt N, Stockman PK, Giagounidis A; SPARK-AML1 Investigators. Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low-dose cytosine arabinoside in elderly patients with acute myeloid leukemia. Cancer. 2013 Jul 15;119(14):2611-9. Epub 2013 Apr 19. link to original article link to PMC article contains dosing details in abstract PubMed NCT00952588
BI 1230.4: Döhner H, Lübbert M, Fiedler W, Fouillard L, Haaland A, Brandwein JM, Lepretre S, Reman O, Turlure P, Ottmann OG, Müller-Tidow C, Krämer A, Raffoux E, Döhner K, Schlenk RF, Voss F, Taube T, Fritsch H, Maertens J. Randomized, phase 2 trial comparing low-dose cytarabine with or without volasertib in AML patients not suitable for intensive induction therapy. Blood. 2014 Aug 28;124(9):1426-33. Epub 2014 Jul 8. link to original article link to PMC article PubMed NCT00804856
Burnett AK, Russell N, Hills RK, Panoskaltsis N, Khwaja A, Hemmaway C, Cahalin P, Clark RE, Milligan D. A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia. Leukemia. 2015 Jun;29(6):1312-9. Epub 2015 Feb 13. link to original article contains dosing details in manuscript PubMed
UK NCRI LI-1: Dennis M, Russell N, Hills RK, Hemmaway C, Panoskaltsis N, McMullin MF, Kjeldsen L, Dignum H, Thomas IF, Clark RE, Milligan D, Burnett AK. Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia. Blood. 2015 May 7;125(19):2923-32. Epub 2015 Mar 24. link to original article contains dosing details in manuscript link to PMC article PubMed ISRCTN40571019
AZA-AML-001: Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01074047
1. Subgroup analysis: Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. link to original article link to PMC article PubMed
BRIGHT AML 1003: Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. link to original article link to PMC article PubMed NCT01546038
1. Update: Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. link to original article link to PMC article PubMed
VIALE-C: Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. link to original article contains dosing details in manuscript link to PMC article PubMed NCT03069352
1. Update: Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. link to original article link to PMC article PubMed
POLO-AML-2: NCT01721876

LoDAC & Venetoclax

LoDAC & Venetoclax: Low Dose Ara-C (Cytarabine) & Venetoclax

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Wei et. al. 2019 (M14-387)	2015-2017	Phase 1b/2 (RT)
Wei et al. 2020 (VIALE-C)	2017-2018	Phase 3 (E-RT-esc)	LoDAC	Seems to have superior OS¹ Median OS: 8.4 vs 4.1 mo (HR 0.70, 95% CI 0.50-0.99)

¹Reported efficacy for VIALE-C is based on the 2021 update.

Chemotherapy

Cytarabine (Ara-C) 20 mg/m² SC once per day on days 1 to 10

Targeted therapy

Venetoclax (Venclexta) as follows:
- Cycle 1: 100 mg PO once on day 1, then 200 mg PO once on day 2, then 400 mg PO once on day 3, then 600 mg PO once per day on days 4 to 28
- Cycle 2 onwards: 600 mg PO once per day

28-day cycles

Dose modifications

M14-387: The dose of venetoclax was reduced by 50% for moderate CYP3A inhibitors and approximately 75% to 90% for strong inhibitors.

References

M14-387: Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019 May 20;37(15):1277-1284. Epub 2019 Mar 20. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02287233
VIALE-C: Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. link to original article contains dosing details in manuscript link to PMC article PubMed NCT03069352
1. Update: Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. link to original article link to PMC article PubMed

Temozolomide monotherapy

Regimen

Study	Years of enrollment	Evidence
Brandwein et al. 2014	NR	Phase 2

Note: Patient selection was based on MGMT expression by Western blot. See article for details.

Chemotherapy

Temozolomide (Temodar) 200 mg/m²/day PO on days 1 to 7
- Complete responders could receive: 200 mg/m²/day PO on days 1 to 5

28-day cycle for up to 12 cycles

References

Brandwein JM, Kassis J, Leber B, Hogge D, Howson-Jan K, Minden MD, Galarneau A, Pouliot JF. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression. Br J Haematol. 2014 Dec;167(5):664-70. Epub 2014 Aug 27. link to original article contains dosing details in abstract PubMed

Consolidation after upfront therapy

5+2d

Regimen

Study	Years of enrollment	Evidence
Lancet et al. 2018 (CLTR0310-301)	2012-2014	Non-randomized portion of phase 3 RCT

Preceding treatment

7+3d; intermediate-dose

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m²)
Daunorubicin (Cerubidine) 60 mg/m² IV once per day on days 1 & 2

5-day course

References

CLTR0310-301: Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. link to original article contains dosing details in abstract link to PMC article PubMed NCT01696084

High-dose Cytarabine monotherapy (HiDAC)

HiDAC: High Dose Ara-C (Cytarabine)
HDAC: High Dose Ara-C (Cytarabine)
HDAraC: High Dose AraC (Cytarabine)

Regimen variant #1, 2000 mg/m² every 12 hours x 6

Study	Years of enrollment	Evidence
Holowiecki et al. 2012 (PALG AML1/2004)	2004-2008	Non-randomized portion of phase 3 RCT

Details in the text are scant.

Preceding treatment

Cytarabine & Mitoxantrone consolidation

Chemotherapy

Cytarabine (Ara-C) 2000 mg/m² IV every 12 hours on days 1, 3, 5 (total dose: 12,000 mg/m²)

5-day course

Regimen variant #2, 2 cycles of 2000 mg/m² every 12 hours x 10

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Fukushima et al. 2012	2002-2006	Randomized, <20 pts in this arm (C)	mIDAC		Seems to be more toxic

Note: length of cycle was not specified in the manuscript; 28-day cycle is typical for this regimen.

Preceding treatment

BHAC-MMV

Chemotherapy

Cytarabine (Ara-C) 2000 mg/m² IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 20,000 mg/m²)

28-day cycle for 2 cycles

Subsequent treatment

A-VVV

Regimen variant #3, 1 cycle of 3000 mg/m² every 12 hours x 12

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cassileth et al. 1998	1990-1995	Phase 3 (C)	BuCy, then auto HSCT	Seems to have superior OS

Preceding treatment

5+2i

Chemotherapy

Cytarabine (Ara-C) 3000 mg/m² IV over 3 hours every 12 hours on days 1 to 6 (total dose: 36,000 mg/m²)

6-day course

Regimen variant #4, 3 cycles of 3000 mg/m² every 12 hours x 6

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Moore et al. 2004 (CALGB 9222)	1992-1995	Phase 3 (C)	HiDAC, then CYVE, then AZQ & Mitoxantrone	Did not meet primary endpoint of DFS
Schaich et al. 2013 (AML2003)	2003-2009	Phase 3 (C)	MAC/MAMAC/MAC	Did not meet primary endpoint of DFS
Petersdorf et al. 2013 (SWOG S0106)	2004-2009	Non-randomized portion of phase 3 RCT
Stone et al. 2015 (ACCEDE)	2008-2010	Non-randomized portion of phase 3 RCT
Röllig et al. 2015 (SORAML)	2009-2011	Randomized Phase 2 (C)	HiDAC & Sorafenib	Seems to have inferior EFS
Stone et al. 2015 (COSAH C-022)	2010-2014	Non-randomized portion of phase 3 RCT

Note: CALGB 9222 specified that each cycle begins within 2 weeks after hematopoietic recovery from the preceding cycle. SORAML specified a 28-day (minimum) cycle or 1 week after marrow recovery, whichever comes later.

Preceding treatment

CALGB 9222: 7+3d; standard-dose
SWOG S0106: 7+3d; intermediate-dose versus 7+3d & GO
AML2003: 7+3d; intermediate-dose x 2
ACCEDE: Amonafide & Cytarabine versus 7+3d; standard-dose
SORAML: 7+3d; intermediate-dose versus 7+3d & Sorafenib
COSAH C-022: 7+3d; high-dose versus 7+3i

Chemotherapy

Cytarabine (Ara-C) 3000 mg/m² IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m²)

3 cycles of varying durations

Subsequent treatment

SWOG S0106: GO maintenance versus no further treatment

Regimen variant #5, 3 cycles of 2000 mg/m² every 12 hours x 10

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ohtake et al. 2010 (JALSG AML201)	2001-2005	Phase 3 (E-de-esc)	Multiagent chemotherapy	Did not meet primary endpoint of DFS

Note: this was considered an experimental arm in Japan, given the timing of HiDAC approval. Reported efficacy is based on the 2010 update by Miyawaki et al.

Preceding treatment

7+5d or 7+3i

Chemotherapy

Cytarabine (Ara-C) 2000 mg/m² IV over 3 hours every 12 hours on days 1 to 5 (total dose per cycle: 10,000 mg/m²)

3 cycles, started 1 week after neutrophils, WBCs, and platelets recovered to more than 1500/uL, 3 × 10⁹/L, and 100 × 10⁹/L

Regimen variant #6, 4 cycles of 3000 mg/m² every 12 hours x 6

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Mayer et al. 1994 (CALGB 8525)	1985-1990	Phase 3 (E-esc)	Low-dose continuous infusion cytarabine	Seems to have superior OS
Thomas et al. 2011 (ALFA-9802)	1999-2006	Phase 3 (C)	Timed sequential chemotherapy (TSC)	Did not meet primary endpoint of EFS
Lee et al. 2017 (COSAH C-022)	2010-2014	Non-randomized portion of phase 3 RCT

Note: cycle length of HiDAC is not specified; 28-day cycle is often used in clinical practice.

Preceding treatment

ALFA-9802: Timed sequential therapy +/- GM-CSF priming
COSAH C-022: 7+3d; high-dose versus 7+3i

Chemotherapy

Cytarabine (Ara-C) 3000 mg/m² IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m²)

28-day cycle for up to 4 cycles

Subsequent treatment

ALFA-9802: Cytarabine & Daunorubicin maintenance

References

CALGB 8525: Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd; CALGB. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. link to original article contains dosing details in manuscript PubMed
Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, Wiernik PH. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998 Dec 3;339(23):1649-56. link to original article contains dosing details in manuscript PubMed
CALGB 9222: Moore JO, George SL, Dodge RK, Amrein PC, Powell BL, Kolitz JE, Baer MR, Davey FR, Bloomfield CD, Larson RA, Schiffer CA. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222. Blood. 2005 May 1;105(9):3420-7. Epub 2004 Nov 30. link to original article link to PMC article contains dosing details in manuscript PubMed
JALSG AML201: Ohtake S, Miyawaki S, Fujita H, Kiyoi H, Shinagawa K, Usui N, Okumura H, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2358-65. Epub 2010 Aug 6. link to original article PubMed C000000157
1. Update: Miyawaki S, Ohtake S, Fujisawa S, Kiyoi H, Shinagawa K, Usui N, Sakura T, Miyamura K, Nakaseko C, Miyazaki Y, Fujieda A, Nagai T, Yamane T, Taniwaki M, Takahashi M, Yagasaki F, Kimura Y, Asou N, Sakamaki H, Handa H, Honda S, Ohnishi K, Naoe T, Ohno R. A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults: the JALSG AML201 Study. Blood. 2011 Feb 24;117(8):2366-72. Epub 2010 Dec 29. link to original article contains dosing details in manuscript PubMed
ALFA-9802: Thomas X, Elhamri M, Raffoux E, Renneville A, Pautas C, de Botton S, de Revel T, Reman O, Terré C, Gardin C, Chelghoum Y, Boissel N, Quesnel B, Hicheri Y, Bourhis JH, Fenaux P, Preudhomme C, Michallet M, Castaigne S, Dombret H. Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study. Blood. 2011 Aug 18;118(7):1754-62. Epub 2011 Jun 20. link to original article contains dosing details in manuscript PubMed NCT00880243
Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. link to original article contains dosing details in manuscript PubMed
SWOG S0106: Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. link to original article link to PMC article PubMed NCT00085709
AML2003: Schaich M, Parmentier S, Kramer M, Illmer T, Stölzel F, Röllig C, Thiede C, Hänel M, Schäfer-Eckart K, Aulitzky W, Einsele H, Ho AD, Serve H, Berdel WE, Mayer J, Schmitz N, Krause SW, Neubauer A, Baldus CD, Schetelig J, Bornhäuser M, Ehninger G. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013 Jun 10;31(17):2094-102. Epub 2013 Apr 29. link to original article contains dosing details in manuscript PubMed NCT00180102
ACCEDE: Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00715637
PALG AML1/2004: Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains dosing details in manuscript PubMed
SORAML: Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. link to original article contains dosing details in abstract PubMed NCT00893373
COSAH C-022: Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. link to original article contains dosing details in manuscript PubMed NCT01145846

Intermediate-dose Cytarabine monotherapy (IDAC)

IDAC: Intermediate Dose Ara-C (Cytarabine)
mIDAC: modified Intermediate Dose Ara-C (Cytarabine)

Regimen variant #1, 1000 mg/m² x 3

Study	Years of enrollment	Evidence
Stone et al. 2015 (ACCEDE)	2008-2010	Non-randomized portion of phase 3 RCT

Preceding treatment

Amonafide & Cytarabine versus 7+3d; standard-dose

Chemotherapy

Cytarabine (Ara-C) 1000 mg/m² IV over 3 hours once per day on days 1, 3, 5 (total dose per cycle: 3000 mg/m²)

3 cycles (length not specified)

Regimen variant #2, 1000 mg/m² x 10

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Fukushima et al. 2012	2002-2006	Randomized, <20 pts in this arm (E-de-esc)	HDAC		Seems to be less toxic

Note: cycle length was not specified; 28-day cycles are frequently used in this setting.

Preceding treatment

BHAC-MMV

Chemotherapy

Cytarabine (Ara-C) 1000 mg/m² IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 10,000 mg/m²)

28-day cycle for 2 cycles (see note)

Subsequent treatment

A-VVV

Regimen variant #3, 1000 mg/m² x 12

Study	Years of enrollment	Evidence
Löwenberg et al. 2009 (HOVON 43 AML/SAKK 30/01)	2000-2006	Non-randomized portion of phase 3 RCT

Preceding treatment

7+3d; standard-dose versus 7+3d; high-dose

Chemotherapy

Cytarabine (Ara-C) 1000 mg/m² IV over 6 hours every 12 hours on days 1 to 6 (total dose: 12,000 mg/m²)

6-day course

Subsequent treatment

Transplant eligible patients: allogeneic HSCT
Transplant ineligible patients: Gemtuzumab ozogamicin maintenance versus no further treatment

References

HOVON 43 AML/SAKK 30/01: Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. link to original article contains dosing details in manuscript PubMed ISRCTN77039377
Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. link to original article contains dosing details in manuscript PubMed
ACCEDE: Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. link to original article contains dosing details in manuscript PubMed NCT00715637

HiDAC & G-CSF

HiDAC & G-CSF: High Dose Ara-C (Cytarabine) & Granulocyte Colony Stimulating Factor

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Thomas et al. 2017 (ALFA-0702)	2009-2013	Randomized Phase 2 (C)	CLARA	Seems to have inferior RFS

Preceding treatment

Cytarabine, Daunorubicin, G-CSF induction

Chemotherapy

Cytarabine (Ara-C) 3000 mg/m² IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m²)

Growth factor therapy

Filgrastim (Neupogen) 5 mcg/kg IV once per day on days 1 to 5

35-day cycle for 3 cycles

References

ALFA-0702: Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. link to original article contains dosing details in supplement PubMed NCT00932412

Azacitidine monotherapy

Regimen

Study	Years of enrollment	Evidence
Nand et al. 2013 (SWOG S0703)	2008-NR	Phase 2

Preceding treatment

Azacitidine & Gemtuzumab ozogamicin consolidation

Chemotherapy

Azacitidine (Vidaza) 75 mg/m² SC once on day 1

28-day cycle for 4 cycles

References

SWOG S0703: Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00658814

Azacitidine & Gemtuzumab ozogamicin

Regimen

Study	Years of enrollment	Evidence
Nand et al. 2013 (SWOG S0703)	2008-NR	Phase 2

Preceding treatment

Azacitidine & Gemtuzumab ozogamicin induction

Chemotherapy

Azacitidine (Vidaza) 75 mg/m² IV or SC once per day on days 1 to 7

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV once on day 8

Supportive therapy

"Appropriate premedications" which were not specified, for Gemtuzumab ozogamicin (Mylotarg)
Growth factors per physician discretion

8-day course

Subsequent treatment

Azacitidine maintenance, within 42 days of completion of consolidation

References

SWOG S0703: Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00658814

BuCy, then auto HSCT

BuCy: Busulfan & Cyclophosphamide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)	1995-2006	Phase 3 (E-esc)	Etoposide & Mitoxantrone	Might have superior RFS

Preceding treatment

7+3i, then Amsacrine & Cytarabine

Chemotherapy

Busulfan (Myleran) 4 mg/kg PO (frequency not specified) on days -7 to -4
Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

Supportive therapy

Autologous stem cells re-infused on day 0

One course

References

HOVON-SAKK AML-29/AML-42: Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. link to original article contains dosing details in manuscript PubMed

BuFlu, then allo HSCT

BuFlu: Busulfan & Fludarabine

Regimen

Study	Years of enrollment	Evidence
Devine et al. 2015 (CALGB 100103)	2004-2011	Phase 2, <20 pts in subgroup
Nand et al. 2013 (SWOG S0703)	2008-NR	Phase 2

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV over 30 minutes once per day on days -7 to -3
- MC-FludT.14/L gave the doses on days -6 to -2
Busulfan (Myleran) 0.8 mg/kg IV over 2 hours every 6 hours on days -4 & -3 (total dose: 6.4 mg/kg)

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

ATG (Rabbit) 2.5 mg/kg IV over 6 hours once per day on days -4 to -2
Tacrolimus (Prograf) with doses adjusted to maintain levels of 5 to 10 ng/mL, tapered on day +90 to off by day +180 (if no GVHD)
Methotrexate (MTX) 5 mg/m² IV once per day on days +1, +3, +6, +11

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

CALGB 100103: Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00070135

CIA

CIA: Clofarabine, Idarubicin, Ara-C (Cytarabine)

Regimen

Study	Years of enrollment	Evidence
Nazha et al. 2013	2010-2012	Phase 2

Preceding treatment

CIA induction

Chemotherapy

Clofarabine (Clolar) 15 mg/m² IV once per day on days 1 to 3
Idarubicin (Idamycin) 8 mg/m² IV once per day on days 1 & 2
Cytarabine (Ara-C) 750 mg/m² IV once per day on days 1 to 3

21- to 28-day cycle for up to 6 cycles; exact timing depends on disease response and recovery from regimen toxicity

References

Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. long link to original article contains dosing details in manuscript link to PMC article PubMed

CLARA

CLARA: CLofarabine and ARA-C (Cytarabine)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Thomas et al. 2017 (ALFA-0702)	2009-2013	Randomized Phase 2 (E-esc)	HiDAC & G-CSF	Seems to have superior RFS

Preceding treatment

Cytarabine, Daunorubicin, G-CSF induction

Chemotherapy

Clofarabine (Clolar) 30 mg/m² IV over 2 hours once per day on days 2 to 6, given first
Cytarabine (Ara-C) 1000 mg/m² IV over 2 hours once per day on days 1 to 5, given second, 4 hours after clofarabine, on days 2 to 5

Growth factor therapy

Filgrastim (Neupogen) 5 mcg/kg IV once per day on days 1 to 6

35-day cycle for 3 cycles

References

ALFA-0702: Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. link to original article contains dosing details in supplement PubMed NCT00932412

Clofarabine & LoDAC/Decitabine

Clofarabine & LoDAC/Decitabine: Clofarabine & Low Dose Ara-C (Cytarabine) alternating with Decitabine

Protocol

Study	Years of enrollment	Evidence
Faderl et al. 2010	2008-2010	Phase 2

Preceding treatment

Clofarabine & LoDAC, which is counted as "Cycle 1". Cycles are given every 4 to 7 weeks pending hematologic recovery and resolution of other toxicities.

Chemotherapy, clofarabine & LoDAC portion

Clofarabine (Clolar) as follows:
- Cycles 2, 3, 7 to 9, 13 to 15: 20 mg/m² IV once per day on days 1 to 3
Cytarabine (Ara-C) as follows:
- Cycles 2, 3, 7 to 9, 13 to 15: 20 mg SC twice per day on days 1 to 7

4- to 7-week cycles, depending on count recovery

Chemotherapy, decitabine portion

Decitabine (Dacogen) as follows:
- Cycles 4 to 6, 10 to 12, 16 to 18: 20 mg/m² IV once per day on days 1 to 5

4- to 7-week cycles, depending on count recovery

References

Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. link to original article contains dosing details in manuscript link to PMC article PubMed
1. Update: Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. link to original article link to PMC article PubMed

CPX-351 monotherapy

CPX-351: Liposomal Cytarabine and Daunorubicin

Regimen

Study	Years of enrollment	Evidence
Lancet et al. 2018 (CLTR0310-301)	2012-2014	Non-randomized portion of phase 3 RCT

Preceding treatment

CPX-351 induction

Chemotherapy

CPX-351 (Vyxeos) 65 units/m² IV over 90 minutes once per day on days 1 & 3

5- to 8-week cycle for 2 cycles

References

CLTR0310-301: Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. link to original article contains dosing details in abstract link to PMC article PubMed NCT01696084

Cytarabine & Daunorubicin

Regimen variant #1

Study	Years of enrollment	Evidence
Castaigne et al. 2012 (ALFA-0701)	2008-2010	Non-randomized portion of phase 3 RCT

Note: the preceding treatment is not a true randomization because only patients in the gemtuzumab ozogamicin arm with platelet count less than 100 x 10⁹ at day 45 from initiation of chemotherapy were assigned to this regimen.

Preceding treatment

7+3d; intermediate-dose or 7+3d & GO induction

Chemotherapy

Cytarabine (Ara-C) 1000 mg/m² IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m²)
Daunorubicin (Cerubidine) as follows:
- Cycle 1: 60 mg/m² IV once on day 1
- Cycle 2: 60 mg/m² IV once per day on days 1 & 2

2 cycles (length not specified)

Regimen variant #2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Gardin et al. 2007 (ALFA 9803)	1999-2006	Phase 3 (E-esc)	4d + 7	Seems to have superior OS

Preceding treatment

4d + 7 induction

Chemotherapy

Cytarabine (Ara-C) 60 mg/m² SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m²)
Daunorubicin (Cerubidine) 45 mg/m² IV once on day 1

1-month cycle for up to 6 cycles

References

ALFA 9803: Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. link to original article contains dosing details in manuscript PubMed NCT00363025
ALFA-0701: Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. link to original article contains dosing details in manuscript PubMed NCT00927498
1. Update: Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. link to original article link to PMC article PubMed

Cytarabine, Daunorubicin, Gemtuzumab ozogamicin

Regimen

Study	Years of enrollment	Evidence
Castaigne et al. 2012 (ALFA-0701)	2008-2010	Non-randomized portion of phase 3 RCT

Preceding treatment

7+3d & GO induction

Chemotherapy

Cytarabine (Ara-C) 1000 mg/m² IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m²)
Daunorubicin (Cerubidine) as follows:
- Cycle 1: 60 mg/m² IV once on day 1
- Cycle 2: 60 mg/m² IV once per day on days 1 & 2

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² (maximum dose of 5 mg) IV once on day 1

2 cycles (length not specified)

References

ALFA-0701: Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. link to original article contains dosing details in manuscript PubMed NCT00927498
1. Update: Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. link to original article link to PMC article PubMed

CYVE

CYVE: CYtarabine & VEpesid (Etoposide)

Regimen

Study	Years of enrollment	Evidence
Lee et al. 2017 (COSAH C-022)	2010-2014	Non-randomized portion of phase 3 RCT

Note: this consolidation regimen was for patients with high-risk cytogenetics.

Preceding treatment

7+3d; high-dose versus 7+3i

Chemotherapy

Cytarabine (Ara-C) 1000 mg/m² IV once per day on days 1 to 6
Etoposide (Vepesid) 150 mg/m² IV once per day on days 1 to 3

4 courses

Subsequent treatment

Transplant eligible patients with available donors usually proceeded to allogeneic HSCT after 2 courses (details not specified)

References

COSAH C-022: Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. link to original article contains dosing details in manuscript PubMed NCT01145846

Cytarabine & Idarubicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Gardin et al. 2007 (ALFA 9803)	1999-2006	Phase 3 (E-esc)	4i + 7	Seems to have superior OS

Preceding treatment

4i + 7 induction

Chemotherapy

Cytarabine (Ara-C) 60 mg/m² SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m²)
Idarubicin (Idamycin) 9 mg/m² IV once on day 1

1-month cycle for up to 6 cycles

References

ALFA 9803: Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. link to original article contains dosing details in manuscript PubMed NCT00363025

Cytarabine, Idarubicin, Sorafenib

Regimen

Study	Years of enrollment	Evidence
Ravandi et al. 2010 (BAY43-9006)	2007-2009	Phase 1/2

Regimen details are from the phase 2 part of the published phase 1/2 trial.

Preceding treatment

7+3i & Sorafenib induction

Chemotherapy

Cytarabine (Ara-C) 750 mg/m²/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 2250 mg/m²)
Idarubicin (Idamycin) 8 mg/m² IV over 60 minutes once per day on days 1 & 2

Targeted therapy

Sorafenib (Nexavar) 400 mg PO twice per day for up to 28 days

4- to 6-week cycle for up to 5 cycles

Subsequent treatment

Sorafenib maintenance

References

BAY43-9006: Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00542971
1. Update: Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. link to original article link to PMC article PubMed

Cyclophosphamide & TBI, then allo HSCT

Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy	Non-relapse mortality
Blume et al. 1980	1976-1979	Non-randomized, <20 pts
Zittoun et al. 1995	1986-1993	Phase 3 (E-esc)	Intensive chemotherapy	Superior DFS
Bornhäuser et al. 2012 (9005-2003)	2004-2009	Phase 3 (C)	Fludarabine & TBI, then allo HSCT	Did not meet secondary efficacy endpoints	Did not meet primary endpoint of NRM

Preceding treatment

Zittoun et al. 1995: 7+3d with CR, then Amsacrine & IDAC

Details in most of the manuscripts are limited.

Chemotherapy

Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2

Radiotherapy

Total body irradiation by the following study-specific criteria:
- Zhang et al. 2023: 450 cGy once per day on days -5 & -4 (900 cGy total)
- Other studies: 10 to 1200 cGy total

Immunotherapy

Allogeneic stem cells transfused on day 0

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. link to original article PubMed
Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; EORTC; GIMEMA. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. link to original article contains dosing details in abstract PubMed
9005-2003: Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. link to original article contains dosing details in abstract PubMed NCT00150878
Retrospective: Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. link to original article link to PMC article PubMed

Etoposide & Mitoxantrone

ME: Mitoxantrone & Etoposide

Regimen variant #1, 3 days

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (AMLSG31-19)	2021-ongoing	Phase 3 (C)	ME & Venetoclax	In progress

Note: this dosing was intended for patients older than 60. Dosing information is from CT.gov.

Preceding treatment

7+3d induction

Chemotherapy

Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Mitoxantrone (Novantrone) 10 mg/m² IV once per day on days 1 to 3

One course

Regimen variant #2, 5 days

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)	1995-2006	Phase 3 (C)	Bu/Cy, then auto HSCT	Might have inferior RFS

Preceding treatment

7+3i, then Amsacrine & Cytarabine

Chemotherapy

Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 5
Mitoxantrone (Novantrone) 10 mg/m² IV once per day on days 1 to 5

One course

References

HOVON-SAKK AML-29/AML-42: Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. link to original article contains dosing details in manuscript PubMed
AMLSG31-19: NCT04628026

Fludarabine & TBI, then allo HSCT

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy	Non-relapse mortality
Bornhäuser et al. 2012 (9005-2003)	2004-2009	Phase 3 (E-switch-ic)	Cyclophosphamide & TBI, then allo HSCT	Did not meet secondary efficacy endpoints	Did not meet primary endpoint of NRM

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV once per day on days -6 to -3

Radiotherapy

Total body irradiation (TBI) 200 cGy fractions x 4 doses on days -3 & -2 (800 cGy total)

Immunotherapy

Allogeneic stem cells transfused on day 0

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

Regimen variant #2, low-dose TBI

Study	Years of enrollment	Evidence
Gyukocza et al. 2010	1998-2008	Non-randomized

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV once per day on days -4 to -2

Radiotherapy

Total body irradiation (TBI) 200 cGy at a rate of 7 cGy/min on day 0

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

Cyclosporine 6.25 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 100 over 80 days (if no GVHD)
Mycophenolate mofetil (CellCept) 15 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 40 over 56 days (if no GVHD)

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. link to original article contains dosing details in manuscript link to PMC article PubMed
9005-2003: Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. link to original article contains dosing details in abstract PubMed NCT00150878

Fludarabine, Busulfan, ATG, then allo HSCT

Regimen

Study	Years of enrollment	Evidence
Devine et al. 2015 (CALGB 100103)	2004-2011	Phase 2

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

CALGB 100103: Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00070135

HAM

HAM: High-dose Ara-C (Cytarabine), Mitoxantrone

Regimen

Study	Years of enrollment	Evidence
Wierzbowksa et al. 2007	NR in abstract	Phase 2
Holowiecki et al. 2012 (PALG AML1/2004)	2004-2008	Non-randomized portion of phase 3 RCT

Preceding treatment

Wierzbowska et al. 2007: CLAG-M
PALG AML1/2004: DA versus DAC versus DAF

Chemotherapy

Cytarabine (Ara-C) 1500 mg/m² IV once per day on days 1 to 3
Mitoxantrone (Novantrone) 10 mg/m² IV once per day on days 3 to 5

Subsequent treatment

HiDAC consolidation

References

Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
PALG AML1/2004: Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. link to original article contains dosing details in manuscript PubMed

IC & Norethandrolone/6-MP, MTX, Norethandrolone

IC & Norethandrolone: Idarubicin, Cytarabine, Norethandrolone

Protocol

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Pigneux et al. 2016 (GOELAMS LAM-SA2002)	2002-2005	Phase 3 (E-esc)	IC/6-MP & MTX	Superior OS

Preceding treatment

7+3i & Lomustine

Chemotherapy, reinduction

Idarubicin (Idamycin) 8 mg/m² IV once on day 1
Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m²)

Endocrince therapy, reinduction

Norethandrolone (Nilevar) by the following weight-based criteria:
- If less than 60 kg: 10 mg PO once per day
- If greater than 60 kg: 20 mg PO once per day

3-month cycle for 6 cycles, alternating with maintenance

Chemotherapy, maintenance

Methotrexate (MTX) by the following weight-based criteria:
- If less than 60 kg: 20 mg PO once per day on days 1, 4, 8, 11
- If greater than 60 kg: 25 mg PO once per day on days 1, 4, 8, 11
Mercaptopurine (6-MP) by the following weight-based criteria:
- If less than 60 kg: 100 mg PO once per day on days 15 to 30
- If greater than 60 kg: 150 mg PO once per day on days 15 to 30

Endocrine therapy, maintenance

Norethandrolone (Nilevar) by the following weight-based criteria:
- If less than 60 kg: 10 mg PO once per day
- If greater than 60 kg: 20 mg PO once per day

3-month cycle for 6 cycles, alternating with re-induction courses

References

GOELAMS LAM-SA2002: Pigneux A, Béné MC, Guardiola P, Recher C, Hamel JF, Sauvezie M, Harousseau JL, Tournilhac O, Witz F, Berthou C, Escoffre-Barbe M, Guyotat D, Fegueux N, Himberlin C, Hunault M, Delain M, Lioure B, Jourdan E, Bauduer F, Dreyfus F, Cahn JY, Sotto JJ, Ifrah N. Addition of androgens improves survival in elderly patients with acute myeloid leukemia: a GOELAMS study. J Clin Oncol. 2017 Feb;35(4):387-393. Epub 2016 Oct 24. link to original article contains dosing details in manuscript PubMed NCT00700544

Low-dose TBI, then allo HSCT

TBI: Total Body Irradiation

Regimen

Study	Years of enrollment	Evidence
Gyukocza et al. 2010	1998-2008	Non-randomized

Radiotherapy

Total body irradiation (TBI) 200 cGy at a rate of 0.07 to 0.2000 cGy/min on day 0

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

One of the following (further details not specified):
- Cyclosporine
- Tacrolimus (Prograf)
Mycophenolate mofetil (CellCept)

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. link to original article contains dosing details in manuscript link to PMC article PubMed

Maintenance after first-line therapy

Note: with a few exceptions, these regimens are given as part of a non-curative line of therapy.

Azacitidine monotherapy

Regimen variant #1, 12 cycles

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Huls et al. 2019 (HOVON97)	2009-2016	Phase 3 (E-esc)	Observation	Superior DFS DFS12: 64% vs 42% (aHR 0.62, 95% CI 0.41-0.95)

Preceding treatment

At least 2 cycles of intensive chemotherapy

Chemotherapy

Azacitidine (Vidaza) 50 mg/m² SC once per day on days 1 to 5

28-day cycle for up to 12 cycles

Regimen variant #2, indefinite

Study	Years of enrollment	Evidence
Grövdal et al. 2010	2004-2006	Phase 2

Intended to be used for transformed MDS patients in remission after AML induction therapy.

Preceding treatment

7+2d

Chemotherapy

Azacitidine (Vidaza) 60 mg/m² SC once per day on days 1 to 5

28-day cycles

References

Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. link to original article contains dosing details in manuscript PubMed
HOVON97: Huls G, Chitu DA, Havelange V, Jongen-Lavrencic M, van de Loosdrecht AA, Biemond BJ, Sinnige H, Hodossy B, Graux C, Kooy RVM, de Weerdt O, Breems D, Klein S, Kuball J, Deeren D, Terpstra W, Vekemans MC, Ossenkoppele GJ, Vellenga E, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group. Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. Blood. 2019 Mar 28;133(13):1457-1464. Epub 2019 Jan 10. link to original article contains dosing details in abstract PubMed NTR1810

Decitabine monotherapy

Regimen

Study	Years of enrollment	Evidence
Blum et al. 2010 (OSU 07017)	2007-NR	Phase 2

Blum et al. 2010 did not clearly state whether decitabine maintenance is at the same dosage/frequency as induction therapy. This is the inferred dosage from the paper.

Preceding treatment

Decitabine induction

Chemotherapy

Decitabine (Dacogen) 20 mg/m² IV over 60 minutes once per day on days 1 to 5
- Patients with no evidence of residual disease by flow cytometry or cytogenetics who had grade 4 neutropenia (ANC less than 500/uL) persisting greater than or equal to 14 days received 4 days instead of 5 days of decitabine starting with the following cycle. If neutropenia occurred again as above with 4 days of decitabine, patients received 3 days instead of 4 days of decitabine starting with the following cycle.

28-day cycles

References

OSU 07017: Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00492401

Azacitidine oral monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Wei et al. 2020 (QUAZAR AML-001)	2013-2017	Phase 3 (E-RT-esc)	Observation	Superior OS¹ Median OS: 24.7 vs 14.8 mo

¹The proportional hazards assumption was violated, so hazard ratios are not reported.

Preceding treatment

Induction chemotherapy

Chemotherapy

Azacitidine oral (Onureg) 300 mg PO once per day on days 1 to 14

28-day cycle

References

QUAZAR AML-001: Wei AH, Döhner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, Ravandi F, Sayar H, Jang JH, Porkka K, Selleslag D, Sandhu I, Turgut M, Giai V, Ofran Y, Kizil Çakar M, Botelho de Sousa A, Rybka J, Frairia C, Borin L, Beltrami G, Čermák J, Ossenkoppele GJ, La Torre I, Skikne B, Kumar K, Dong Q, Beach CL, Roboz GJ; QUAZAR AML-001 Trial Investigators. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med. 2020 Dec 24;383(26):2526-2537. link to original article contains dosing details in abstract PubMed NCT01757535

Gemtuzumab ozogamicin monotherapy

Regimen

Study	Years of enrollment	Evidence
Amadori et al. 2016 (EORTC/GIMEMA AML-19)	2004-2013	Non-randomized portion of phase 3 RCT

Preceding treatment

Gemtuzumab ozogamicin induction, with clinical benefit

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 2 mg/m² IV once on day 1

1-month cycle for up to 8 cycles

References

EORTC/GIMEMA AML-19: Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. link to original article contains dosing details in manuscript PubMed NCT00091234

Low-dose Cytarabine monotherapy (LoDAC)

LoDAC: Low Dose Ara-C (cytarabine)
LDAC: Low Dose Ara-C (cytarabine)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Robles et al. 2000 (ECOG E5483)	1984-1988	Phase 3 (E-esc)	Observation	Might have superior DFS

Preceding treatment

HiDAC, then amsacrine induction

Chemotherapy

Cytarabine (Ara-C) 10 mg/m² SC twice per day on days 1 to 21

8-week cycles

References

ECOG E5483: Robles C, Kim KM, Oken MM, Bennett JM, Letendre L, Wiernik PH, O'Connell MJ, Cassileth PA. Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483). Leukemia. 2000 Aug;14(8):1349-53. link to original article contains dosing details in abstract PubMed

Sorafenib monotherapy

Regimen

Study	Years of enrollment	Evidence
Ravandi et al. 2010 (BAY43-9006)	2007-2009	Phase 1/2

Preceding treatment

Cytarabine, Idarubicin, Sorafenib consolidation

Targeted therapy

Sorafenib (Nexavar) 400 mg PO twice per day

Up to one year course, including consolidation

References

BAY43-9006: Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00542971
1. Update: Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. link to original article link to PMC article PubMed

Relapsed or refractory, salvage therapy

Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.

5+2d

Regimen

Study	Years of enrollment	Evidence
Zeidner et al. 2015 (JHOC-J1101)	2011-2013	Non-randomized portion of phase 2 RCT

Preceding treatment

7+3d; high-dose

Chemotherapy

Cytarabine (Ara-C) 100 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m²)
Daunorubicin (Cerubidine) 45 mg/m² IV once per day on days 1 & 2

5-day course

References

JHOC-J1101: Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01349972

ADE (standard-dose Ara-C)

ADE: Ara-C (Cytarabine), Daunorubicin, Etoposide

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Milligan et al. 2006 (MRC AML-HR)	1998-2003	Phase 3 (C)	FLA	Seems to have superior OS

Chemotherapy

Cytarabine (Ara-C) as follows:
- Course 1: 100 mg/m² IV push every 12 hours on days 1 to 10 (total dose: 2000 mg/m²)
- Course 2: 100 mg/m² IV push every 12 hours on days 1 to 8 (total dose: 1600 mg/m²)
Daunorubicin (Cerubidine) 50 mg/m² IV once per day on days 1, 3, 5
Etoposide (Vepesid) 100 mg/m² IV over 60 minutes once per day on days 1 to 5

2 courses (length not specified)

References

MRC AML-HR: Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK; NCRI Haematological Oncology Clinical Studies Group. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood. 2006 Jun 15;107(12):4614-22. Epub 2006 Feb 16. link to original article PubMed NCT00005863

CLAG

CLAG: CLadribine, Ara-C (Cytarabine), G-CSF

Regimen

Study	Years of enrollment	Evidence
Robak et al. 2000	NR in abstract	Phase 2

Chemotherapy

Cladribine (Leustatin) 5 mg/m² IV over 2 hours once per day on days 1 to 5, given first
Cytarabine (Ara-C) 2000 mg/m² IV over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine

Growth factor therapy

Filgrastim (Neupogen) 300 mcg SC once per day on days -1 to 5 (first dose is given 24 hours before first dose of cladribine)

References

Robak T, Wrzesień-Kuś A, Lech-Marańda E, Kowal M, Dmoszyńska A. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000 Sep;39(1-2):121-9. link to original article contains dosing details in manuscript PubMed
Retrospective: Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. PubMed

CLAG-M

CLAG-M: CLadribine, Ara-C (Cytarabine), G-CSF, Mitoxantrone

Regimen

Study	Years of enrollment	Evidence
Wierzbowksa et al. 2007	NR in abstract	Phase 2

Chemotherapy

Cladribine (Leustatin) 5 mg/m² IV over 2 hours once per day on days 1 to 5, given first
Cytarabine (Ara-C) 2000 mg/m² IV over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine
Mitoxantrone (Novantrone) 10 mg/m² IV once per day on days 1 to 3

Growth factor therapy

Filgrastim (Neupogen) by the following criteria:
- WBC count less than or equal to 20 x 10⁹/L: 300 mcg SC once per day on days 0 to 5, started 24 hours prior to chemotherapy
- WBC count greater than 20 x 10⁹/L: 300 mcg SC once per day on days 1 to 5, started simultaneously to cladribine

6-day course

Subsequent treatment

Patients with PR were recommended to undergo a second course of CLAG-M.
- Primary refractory patients achieving CR after 2nd CLAG-M: HAM consolidation
Others could receive another course of CLAG-M or HAM consolidation per investigator discretion

References

Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
Retrospective: Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. PubMed

CLARA

CLARA: CLofarabine and ARA-C (Cytarabine)
GCLAC: G-CSF, Clofarabine, Ara-C (Cytarabine)

Regimen

Study	Years of enrollment	Evidence
Becker et al. 2011 (UW 6562)	2007-NR	Phase 2

Chemotherapy

Clofarabine (Clolar) 25 mg/m² IV over 60 minutes once per day on days 1 to 5, given first
Cytarabine (Ara-C) 2000 mg/m² IV over 4 hours once per day on days 1 to 5, given second, 4 hours after start of clofarabine infusion

Growth factor therapy

Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting day -1, continuing until ANC at least 2000/uL for 2 consecutive days

6-day course

Subsequent treatment

Patients with greater than 5% blasts at day 21: CLARA re-induction x 1
Patients achieving CR: Optional CLARA consolidation for up to 2 cycles

References

UW 6562: Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011 Oct;155(2):182-9. Epub 2011 Aug 18. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00602225

Clofarabine & Cytarabine

Regimen variant #1, 20/20 variant 1

Study	Years of enrollment	Evidence
Buckley et al. 2015 (FHCRC 2302.00)	2009-2013	Phase 1/2

Note: The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.

Chemotherapy

Clofarabine (Clolar) 20 mg PO once per day on days 1 to 5
Cytarabine (Ara-C) 20 mg/m² SC twice per day on days 1 to 10

Cycle duration not explicitly defined; presumably 28 days

Regimen variant #2, 20/20 variant 2

Study	Years of enrollment	Evidence
Buckley et al. 2015 (FHCRC 2302.00)	2009-2013	Phase 1/2

Note: The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.

Chemotherapy

Clofarabine (Clolar) 20 mg PO once per day on days 1 to 5
Cytarabine (Ara-C) 20 mg/m² SC once per day on days 1 to 14

Cycle duration not explicitly defined; presumably 28 days

Regimen variant #3, 30/1000

Study	Years of enrollment	Evidence
Middeke et al. 2015 (BRIDGE)	2012-2013	Phase 2

Chemotherapy

Clofarabine (Clolar) 30 mg/m² IV once per day on days 1 to 5
Cytarabine (Ara-C) 1000 mg/m² IV once per day on days 1 to 5

At least one cycle

Subsequent treatment

Chemo-responsive patients: Clofarabine & Melphalan, then allo HSCT

Regimen variant #4, 40/1000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Faderl et al. 2004	NR	Phase 1/2
Agura et al. 2011 (Baylor 004-145)	2005-2006	Phase 2
Faderl et al. 2012 (CLASSIC I)	2006-2009	Phase 3 (E-esc)	IDAC	Did not meet primary endpoint of OS

Note: length of cycles was not specified; 28-day cycle is typical for this regimen.

Chemotherapy

Clofarabine (Clolar) 40 mg/m² IV over 60 minutes once per day on days 1 to 5, given first
- Note: in Faderl et al. 2004, clofarabine was given on days 2 to 6
Cytarabine (Ara-C) 1000 mg/m² IV over 2 hours once per day on days 1 to 5, given second, 3 to 4 hours after completion of clofarabine infusion

Supportive therapy

Best described in Agura et al. 2011
Dexamethasone (Decadron) 10 mg IV once per day
5-HT3 antagonists on each day of chemotherapy
Hydration at 150 mL/m²/H "to prevent tumor lysis syndrome" during chemotherapy
Bumetanide (Bumex) 2 to 4 mg IV push once to twice per day as needed to keep weight within 1 kg of patient's initial weight
Levofloxacin (Levaquin) 500 mg IV or PO once per day
Acyclovir (Zovirax) 500 mg IV Q12H
One of the following antifungals:
- Caspofungin (Cancidas) 50 mg IV once per day
- Voriconazole (Vfend) 200 mg (route not specified) twice per day
Parenteral nutrition allowed
No routine use of growth factors

28-day cycle for 1 to 4 cycles

Subsequent treatment

See individual papers for details

References

Faderl S, Gandhi V, O'Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005 Feb 1;105(3):940-7. Epub 2004 Oct 14. link to original article contains dosing details in manuscript PubMed
Baylor 004-145: Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist. 2011;16(2):197-206. Epub 2011 Jan 27. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00334074
CLASSIC I: Faderl S, Wetzler M, Rizzieri D, Schiller G, Jagasia M, Stuart R, Ganguly S, Avigan D, Craig M, Collins R, Maris M, Kovacsovics T, Goldberg S, Seiter K, Hari P, Greiner J, Vey N, Recher C, Ravandi F, Wang ES, Vasconcelles M, Huebner D, Kantarjian HM. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. Epub 2012 May 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00317642
FHCRC 2302.00: Buckley SA, Mawad R, Gooley TA, Becker PS, Sandhu V, Hendrie P, Scott BL, Wood BL, Walter RB, Smith K, Dean C, Estey EH, Pagel JM. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age. Br J Haematol. 2015 Aug;170(3):349-55. Epub 2015 Apr 8. link to original article contains dosing details in manuscript PubMed
BRIDGE: Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. link to original article contains dosing details in abstract PubMed

Etoposide & Mitoxantrone

Regimen

Study	Years of enrollment	Evidence	Efficacy
Ho et al. 1988	1984-1987	Phase 2	ORR: 54%

Chemotherapy

Etoposide (Vepesid) 100 mg/m² IV over 30 minutes once per day on days 1 to 5
Mitoxantrone (Novantrone) 10 mg/m² IV over 15 minutes once per day on days 1 to 5

References

Ho AD, Lipp T, Ehninger G, Illiger HJ, Meyer P, Freund M, Hunstein W. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. J Clin Oncol. 1988 Feb;6(2):213-7. link to original article PubMed

FLAG

FLAG: FLudarabine, Ara-C (Cytarabine), G-CSF

Regimen

Study	Years of enrollment	Evidence
Montillo et al. 1998	1994-1996	Phase 2

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV over 30 minutes once per day on days 1 to 5, given first
Cytarabine (Ara-C) 2000 mg/m² IV over 4 hours once per day on days 1 to 5, given second, 4 hours after the start of fludarabine

Growth factor therapy

G-CSF with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery
- Lenograstim (Granocyte) 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery

6-day course

References

Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F. Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol. 1998 Jun;58(2):105-9. link to original article contains dosing details in manuscript PubMed

FLAG-Ida

FLAG-Ida: FLudarabine, Ara-C (Cytarabine), G-CSF (Filgrastim), Idarubicin

Regimen

Study	Years of enrollment	Evidence
Parker et al. 1997	1995-1997	Phase 2, <20 patients
Pastore et al. 2003	1998-2002	Phase 2

Note: although this regimen is described as FLAG-Ida, the G-CSF starts on day 6 and is therefore considered as a supportive medication, not an antineoplastic.

Chemotherapy

Fludarabine (Fludara) 30 mg/m² IV over 30 minutes once per day on days 1 to 5, given first
Cytarabine (Ara-C) 2000 mg/m² IV over 4 hours once per day on days 1 to 5, given second, 4 hours after fludarabine
Idarubicin (Idamycin) 10 mg/m² IV once per day on days 1 to 3

Supportive therapy

Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6, to continue until neutrophil recovery

5-day course

References

Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM, Samaratunga IR, Grace R, Gover PA, Mufti GJ. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997 Dec;99(4):939-44. link to original article PubMed
Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. Epub 2003 Mar 15. link to original article contains dosing details in abstract PubMed

F-SHAI

F-SHAI: Fludarabine, Sequential High-dose Ara-C (cytarabine), Idarubicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Fiegl et al. 2013	NR	Phase 3 (E-esc)	SHAI	Seems to have superior TTTF

Chemotherapy

Fludarabine (Fludara) 15 mg/m² IV twice per day on days 1, 2, 8, 9, given 4 hours prior to each cytarabine dose
Cytarabine (Ara-C) 1000 mg/m² IV twice per day on days 1, 2, 8, 9
- Dose increased to 3000 mg/m² for patients 60 or younger with refractory AML or greater than or equal to 2nd relapse
Idarubicin (Idamycin) 10 mg/m² IV once per day on days 3, 4, 10, 11

Supportive therapy

G-CSF 5 mcg/kg SC once per day, starting on day 14 and continuing until ANC greater than 1500/uL
- Discontinued if the post-treatment bmbx had greater than 5% bone marrow blasts

11-day course

References

Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W. Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. Epub 2013 Oct 22. link to original article contains dosing details in manuscript PubMed

Gemtuzumab ozogamicin monotherapy

Regimen variant #1, fractionated dosing

Study	Years of enrollment	Evidence
Taksin et al. 2006 (MyloFrance-1)	2005	Phase 2 (RT)

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 3 mg/m² IV once per day on days 1, 4, 7

One course

Regimen variant #2

Study	Years of enrollment	Evidence
Sievers et al. 2001	1997-1999	Phase 2 (RT)

Note: this is one of the trials that led to FDA accelerated approval in 2000; a subsequent confirmatory trial was negative. Due to the high toxicities at this dosing level, this variant should be considered of historical interest, only.

Antibody-drug conjugate therapy

Gemtuzumab ozogamicin (Mylotarg) 9 mg/m² IV once on day 1

14-day cycle for 2 cycles

References

Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. link to original article contains dosing details in abstract PubMed
1. Update: Larson RA, Boogaerts M, Estey E, Karanes C, Stadtmauer EA, Sievers EL, Mineur P, Bennett JM, Berger MS, Eten CB, Munteanu M, Loken MR, Van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia. 2002 Sep;16(9):1627-36. link to original article PubMed
2. Update: Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, Theobald M, Voliotis D, Bennett JM, Richie M, Leopold LH, Berger MS, Sherman ML, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005 Oct 1;104(7):1442-52. link to original article PubMed
MyloFrance-1: Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, Bouabdallah R, Pautas C, Turlure P, Reman O, Gardin C, Varet B, de Botton S, Pousset F, Farhat H, Chevret S, Dombret H, Castaigne S. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007 Jan;21(1):66-71. Epub 2006 Oct 19. link to original article contains dosing details in manuscript PubMed

High-dose Cytarabine monotherapy (HiDAC)

HiDAC: High Dose Ara-C (Cytarabine)

Regimen variant #1, CI

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Giles et al. 2009 (VION-CLI-037)	2005-2007	Phase 3 (C)	HiDAC & Laromustine	Mixed response (see note)

Note: while the experimental arm of this trial met the primary endpoint of ORR, the control arm had superior PFS.

Chemotherapy

Cytarabine (Ara-C) 1500 mg/m²/day IV continuous infusion over 72 hours, started on day 1 (total dose: 7500 mg/m²)

3-day course

Regimen variant #2, intermittent

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Karanes et al. 1999 (SWOG-8326)	1985-1992	Phase 3 (C)	HiDAC & Mitoxantrone	Did not meet primary endpoint of CR rate

Chemotherapy

Cytarabine (Ara-C) 3000 mg/m² IV every 12 hours on days 1 to 6 (total dose: 36,000 mg/m²)

6-day course

References

SWOG-8326: Karanes C, Kopecky KJ, Head DR, Grever MR, Hynes HE, Kraut EH, Vial RH, Lichtin A, Nand S, Samlowski WE, Appelbaum FR. A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res. 1999 Sep;23(9):787-94. link to original article contains dosing details in abstract PubMed
VION-CLI-037: Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S. Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse. Blood. 2009 Nov 5;114(19):4027-33. Epub 2009 Aug 26. link to original article contains dosing details in manuscript PubMed NCT00112554

MAC

MAC: Mitoxantrone & Ara-C (Cytarabine)
MIDAC: Mitoxantrone & Intermediate-Dose Ara-C (Cytarabine)

Regimen variant #1, 6000/25

Study	Years of enrollment	Evidence
Sternberg et al. 2000	1990-1997	Phase 2

Chemotherapy

Mitoxantrone (Novantrone) 5 mg/m² IV bolus once per day on days 1 to 5
Cytarabine (Ara-C) 500 mg/m² IV over 90 minutes every 12 hours on days 1 to 6 (total dose: 6000 mg/m²)

6-day course

Regimen variant #2, 10,000/48

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Solary et al. 1996	1992-1995	Phase 3 (C)	Cytarabine, Mitoxantrone, Quinine	Did not meet primary endpoint of CR rate

Chemotherapy

Mitoxantrone (Novantrone) 12 mg/m² IV bolus once per day on days 2 to 5
Cytarabine (Ara-C) 1000 mg/m² IV every 12 hours on days 1 to 5 (total dose: 10,000 mg/m²)

5-day course

References

Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY, Sadoun A, Pignon B, Berthou C, Maloisel F, Guyotat D, Casassus P, Ifrah N, Lamy Y, Audhuy B, Colombat P, Harousseau JL. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood. 1996 Aug 15;88(4):1198-205. link to original article contains dosing details in abstract PubMed
Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer. 2000 May 1;88(9):2037-41. link to original article contains dosing details in manuscript PubMed

MEC

MEC: Mitoxantrone, Etoposide, Cytarabine

Regimen variant #1, 6/80/1000

Study	Years of enrollment	Evidence
Amadori et al. 1991	1988-1990	Phase 2

Chemotherapy

Mitoxantrone (Novantrone) 6 mg/m² IV bolus once per day on days 1 to 6
Etoposide (Vepesid) 80 mg/m² IV over 60 minutes once per day on days 1 to 6
Cytarabine (Ara-C) 1000 mg/m² IV over 6 hours once per day on days 1 to 6

6-day course

Regimen variant #2, 8/80/1000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Feldman et al. 2005	1999-2001	Phase 3 (C)	MEC & Lintuzumab	Did not meet primary endpoint of ORR

Chemotherapy

Mitoxantrone (Novantrone) 8 mg/m² IV once per day on days 1 to 6
Etoposide (Vepesid) 80 mg/m² IV once per day on days 1 to 6
Cytarabine (Ara-C) 1000 mg/m² IV once per day on days 1 to 6

6-day course

Regimen variant #3, 8/100/1000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Greenberg et al. 2004 (ECOG E2995)	NR-1999	Phase 3 (C)	MEC & Valspodar	Did not meet primary endpoint of CR rate
Cortes et al. 2014 (CLTR0308-205)	2009-NR	Randomized Phase 2 (C)	CPX-351	Did not meet primary endpoint of OS12

Note: this was the most commonly used salvage regimen in the control arm of CLTR0308-205; exact dosing details were not described in the paper.

Chemotherapy

Mitoxantrone (Novantrone) 8 mg/m² IV push once per day on days 1 to 5, given third
Etoposide (Vepesid) 100 mg/m² IV over 2 hours once per day on days 1 to 5, given first
Cytarabine (Ara-C) 1000 mg/m² IV once per day on days 1 to 5, given second

28-day cycle for 1 to 2 cycles

References

Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991 Jul;9(7):1210-4. link to original article PubMed
ECOG E2995: Greenberg PL, Lee SJ, Advani R, Tallman MS, Sikic BI, Letendre L, Dugan K, Lum B, Chin DL, Dewald G, Paietta E, Bennett JM, Rowe JM. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol. 2004 Mar 15;22(6):1078-86. Erratum in: J Clin Oncol. 2004 Jul 1;22(13):2747. link to original article link to PMC article contains dosing details in manuscript PubMed
Feldman EJ, Brandwein J, Stone R, Kalaycio M, Moore J, O'Connor J, Wedel N, Roboz GJ, Miller C, Chopra R, Jurcic JC, Brown R, Ehmann WC, Schulman P, Frankel SR, De Angelo D, Scheinberg D. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol. 2005 Jun 20;23(18):4110-6. link to original article contains dosing details in manuscript PubMed
CLTR0308-205: Cortes JE, Goldberg SL, Feldman EJ, Rizzeri DA, Hogge DE, Larson M, Pigneux A, Recher C, Schiller G, Warzocha K, Kantarjian H, Louie AC, Kolitz JE. Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer. 2015 Jan 15;121(2):234-42. Epub 2014 Sep 15. link to original article link to PMC article PubMed NCT00822094
D18-11141: NCT03926624

Consolidation after salvage therapy

BuCy, then allo HSCT

BuCy: Busulfan & Cyclophosphamide

Regimen variant #1, 12.8/120

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Rambaldi et al. 2015 (GITMO-AMLR2)	2008-2012	Phase 3 (C)	BuFlu, then allo HSCT	Seems to have inferior 1-year non-relapse mortality
Scott et al. 2017 (BMT CTN 0901)	2011-2014	Phase 3 (E-esc)	RIC allo HSCT	Might have superior OS

Chemotherapy

Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4 (total dose: 12.8 mg/kg)
Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 and -2 (total dose: 120 mg/kg)

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

Cyclosporine
Methotrexate (MTX) "according to the discretion of the attending physician"

Supportive therapy

Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

Regimen variant #2, 16/200

Study	Years of enrollment	Evidence
Santos et al. 1983	1975-1982	Non-randomized

Note: the day of allogeneic stem cell transplant is not specified in the protocol.

Chemotherapy

Busulfan (Myleran) 1 mg/kg IV every 6 hours on days 1 to 4 (total dose: 16 mg/kg)
Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days 5 to 8 (total dose: 200 mg/kg)

Immunotherapy

Allogeneic stem cells transfused on unspecified day

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. link to original article contains dosing details in abstract PubMed
GITMO-AMLR2: Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. link to original article PubMed NCT01191957
BMT CTN 0901: Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. Epub 2017 Feb 13. link to original article link to PMC article PubMed NCT01339910

BuFlu, then allo HSCT

BuFlu: Busulfan & Fludarabine
Flu/Bu: Fludarabine & Busulfan

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Rambaldi et al. 2015 (GITMO-AMLR2)	2008-2012	Phase 3 (E-switch-ic)	BuCy, then allo HSCT	Seems to improve 1 & 2 year NRM, similar OS

Chemotherapy

Busulfan (Myleran) 0.8 mg/kg IV four times per day for 2 hour infusions on days -6 to -3
Fludarabine (Fludara) 30 mg/m² IV once per day on days -6 to -3

GVHD prophylaxis, pre-transplant

Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
- Matched unrelated donors: 0.5 mg/kg IV once on day -3, then 2 mg/kg IV once on day -2, then 2.5 mg/kg IV once on day -1
- Mismatched donors: total ATG dose could be increased to 7.5 mg/kg

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis, post-transplant

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

Regimen variant #2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Andersson et al. 2008	1997-2005	Non-randomized		Suggested improved outcomes, but shorter follow up

Chemotherapy

Busulfan (Myleran) 130 mg/m² IV over 3 hours once per day on days -6 to -3
- Dosing targeted for optimal pharmacokinetics but different parameters each institution, please consult the original publication for optimal levels
Fludarabine (Fludara) 40 mg/m² IV over 60 minutes once per day on days -6 to -3, given first

GVHD prophylaxis, pre-transplant

Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
- Unrelated or mismatched donors: 0.5 mg/kg IV once on day -3, then 1.5 mg/kg IV once on day -2, then 2 mg/kg IV once on day -1

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis, post-transplant

#1 Tacrolimus & methotrexate based (Andersson et al.)

Supportive therapy

All patients received Filgrastim (Neupogen) SC once per day from day +7 until achieving an absolute neutrophil count (ANC) ≥1.5 x 10⁹/L for three days
Phenytoin (Dilantin) prophylaxis used during and for one day after IV busulfan

#2 Post-Transplant Cy based (Kanakry et al. and FHCC 2541.00)

GVHD prophylaxis

Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days +3 & +4 (used alone in Kanakry et al. when all patients received bone marrow grafts)
± Cyclosporine intravenous loading dose of CSP was given on day 5, followed by subsequent twice per day dosing adjusted to maintain whole blood trough at 120 to 360 ng/mL. In abscence of GVHD Cyclosporine was tapered from day +56 through day +126 (used in FHCC 2541.00 with PBSCT grafts)

Supportive therapy

Mesna (Mesnex) given with cyclophosphamide

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

Regimen variant #3

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lee et al. 2012 (COSAH C-005)	2005-2009	Phase 3 (E-switch-ic)	BuCy, then allo HSCT	Seems to have inferior OS

Chemotherapy

Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4, given first on days overlapping with fludarabine (total dose: 12.8 mg/kg)
Fludarabine (Fludara) 30 mg/m² IV once per day on days -6 to -2, given second on days overlapping with busulfan

Immunotherapy

Allogeneic stem cells transfused on day 0

GVHD prophylaxis

"Cyclosporine
Methotrexate (MTX) "according to the discretion of the attending physician"

Supportive therapy

Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. link to original article link to PMC article contains dosing details in manuscript Pubmed
COSAH C-005: Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. link to original article contains dosing details in manuscript PubMed NCT00774280
GITMO-AMLR2: Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. link to original article PubMed NCT01191957

Clofarabine & Melphalan, then allo HSCT

Regimen

Study	Years of enrollment	Evidence
Middeke et al. 2015 (BRIDGE)	2012-2013	Phase 2

Limited details are available in the abstract. Treatment is meant to be given during aplasia.

Preceding treatment

Clofarabine & Cytarabine salvage

Chemotherapy

Clofarabine (Clolar) 4 x 30 mg/m² IV
Melphalan (Alkeran) 140 mg/m² IV

Immunotherapy

Allogeneic stem cells transfused on unspecified day

One course

Immunotherapy

Allogeneic stem cells

Stem cells transfused on day 0

References

BRIDGE: Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. link to original article contains dosing details in abstract PubMed

Relapsed or refractory, subsequent lines of therapy

Note: these regimens are generally intended to delay progression of disease and are of non-curative intent.

Azacitidine monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Thepot et al. 2010	2004-2009	Phase 2
Roboz et al. 2014 (CLAVELA)	2010-2012	Phase 3 (C)	Elacytarabine	Did not meet primary endpoint of OS

Note: CLAVELA does not contain precise dosing information for the control arm regimens.

Chemotherapy

Azacitidine (Vidaza) 75 mg/m² SC once per day on days 1 to 7

28-day cycle for at least 4 cycles

References

Thepot S, Itzykson R, Seegers V, Raffoux E, Quesnel B, Chait Y, Sorin L, Dreyfus F, Cluzeau T, Delaunay J, Sanhes L, Eclache V, Dartigeas C, Turlure P, Harel S, Salanoubat C, Kiladjian JJ, Fenaux P, Adès L; Groupe Francophone des Myelodysplasies. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010 Nov 11;116(19):3735-42. Epub 2010 Jul 27. link to original article PubMed
CLAVELA: Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss Ø, Vetrhusand S, Giles FJ. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2014 Jun 20;32(18):1919-26. Epub 2014 May 19. link to original article does not contain dosing details PubMed NCT01147939

Ruxolitinib monotherapy

Regimen

Study	Years of enrollment	Evidence
Eghtedar et al. 2012 (MDACC 2007-0925)	2008-2010	Phase 2

Targeted therapy

Ruxolitinib (Jakafi) 25 mg PO twice per day
- Patients with progression were allowed to increase the dose to 50 mg PO twice per day

28-day cycles

References

MDACC 2007-0925: Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C, Faderl S, Ferrajoli A, Borthakur G, George S, Scherle PA, Newton RC, Kantarjian HM, Ravandi F. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012 May 17;119(20):4614-8. Epub 2012 Mar 15. link to original article contains dosing details in manuscript link to PMC article PubMed

Response criteria

NCI-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia (1990)

Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD, Brunning R, Gale RP, Grever MR, Keating MJ, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990 May;8(5):813-9. link to original article PubMed

Revised International Working Group recommendations (2003)

Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. Erratum in: J Clin Oncol. 2004 Feb 1;22(3):576. LoCocco, Francesco [corrected to Lo-Coco, Francesco]. link to original article PubMed

Prognosis

Prognostic Index for Adult Patients With Acute Myeloid Leukemia in First Relapse (2005)

Relapse-free interval from first complete remission
- Greater than 18 months (0 points)
- 7 to 18 months (3 points)
- Less than or equal to 6 months (5 points)
Cytogenetics at diagnosis
- t(16;16) or inv(16) with or without additional cytogenetic abnormalities (0 points)
- t(8;21) with or without additional cytogenetic abnormalities (3 points)
- Normal, intermediate, unfavorable, or unknown cytogenetics (5 points)
Age at time of first relapse
- Less than or equal to 35 years (0 points)
- 36 to 45 years (1 point)
- Greater than 45 years (2 points)
Stem cell transplantation performed before first relapse
- No (0 points)
- Yes, autologous or allogeneic (2 points)

Risk stratification:

1 to 6 points: Favorable risk (1-year OS of 70%; 5-year OS of 46%)
7 to 9 points: Intermediate risk (1-year OS of 49%; 5-year OS of 18%)
10 to 14 points: Poor risk (1-year OS of 16%; 5-year OS of 4%)

References

Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, Vellenga E, De Greef GE, Jacky E, Van der Lelie J, Boogaerts MA, Löwenberg B. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005 Mar 20;23(9):1969-78. Epub 2005 Jan 4. link to original article PubMed

Prognosis in cytogenetically normal AML

Seminal paper comparing the mutational status of NPM1, FLT3, CEBPA, MLL, and NRAS with clinical outcome: Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008 May 1;358(18):1909-18. link to original article PubMed
CEBPA double mutations: Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009 Mar 26;113(13):3088-91. Epub 2009 Jan 26. link to original article link to PMC article PubMed

Whole genome sequencing

Seminal paper comparing WGS to cytogenetic analysis: Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S, Bohannon A, Kruchowski S, Garza J, Du F, Hughes AEO, Robinson J, Hughes E, Heath SE, Baty JD, Neidich J, Christopher MJ, Jacoby MA, Uy GL, Fulton RS, Miller CA, Payton JE, Link DC, Walter MJ, Westervelt P, DiPersio JF, Ley TJ, Spencer DH. Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers. N Engl J Med. 2021 Mar 11;384(10):924-935. link to original article PubMed

Investigational agents

These are drugs under study with at least some promising results for this disease.

Additional information

@@ Line 17: / Line 17: @@
 |}
 {{TOC limit|limit=3}}
 =Guidelines=
 ==ASH==
 *'''2020:''' Sekeres et al. [https://ashpublications.org/bloodadvances/article/4/15/3528/461693/American-Society-of-Hematology-2020-guidelines-for American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults]
 ==ELN==
 *'''2022:''' Döhner et al. [https://doi.org/10.1182/blood.2022016867 Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN]
@@ Line 28: / Line 25: @@
 *'''2017:''' Döhner et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291965/ Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel]
 *'''2010:''' Döhner et al. [https://doi.org/10.1182/blood-2009-07-235358 Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet]
 ==[http://www.esmo.org/ ESMO]==
 *'''2020:''' Heuser et al. [https://doi.org/10.1016/j.annonc.2020.02.018 Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 ===Older===
 *'''2013:''' Fey et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Acute-Myeloblastic-Leukaemia-in-Adult-Patients Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 =="How I Treat"==
 *'''2020:''' DeWolf & Tallman [https://doi.org/10.1182/blood.2019001982 How I treat relapsed or refractory AML]
 *'''2020:''' DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020 Jan 9;135(2):85-96. [https://doi.org/10.1182/blood.2019001239 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31765470 PubMed]
@@ Line 44: / Line 35: @@
 *'''2015:''' Röllig C, Ehninger G. How I treat hyperleukocytosis in acute myeloid leukemia. Blood. 2015 May 21;125(21):3246-52. Epub 2015 Mar 16. [http://www.bloodjournal.org/content/125/21/3246.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25778528 PubMed]
 *'''2014:''' Ossenkoppele G, Löwenberg B. How I treat the older patient with acute myeloid leukemia. Blood. 2015 Jan 29;125(5):767-74. Epub 2014 Dec 16. [http://www.bloodjournal.org/content/125/5/767.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25515963 PubMed]
 ==[https://www.nccn.org/ NCCN]==
 *[https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf NCCN Guidelines - Acute Myeloid Leukemia]
 ==Antifungal prophylaxis==
 *'''2022:''' Stemler et al. [https://doi.org/10.1016/S2352-3026(22)00073-4 Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association]
 ===Older===
 *'''2015:''' Halpern et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692139/ Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia]
 =Upfront induction therapy, standard and older "fit" patients=
 ''These are aggressive remission induction regimens given with curative intent.''
 ==7+3d (standard-dose) {{#subobject:9f31ad|Regimen=1}}==
 +3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
 <br>AD: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>D</u>'''aunorubicin
 <br>DA: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 700/135 (CI Ara-C) {{#subobject:bb27bc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 183: / Line 169: @@
 |}
 ''Note: this was the lower bound of the allowable daunorubicin dose in AZA-AML-001.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *ECOG E3993, patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of [[#7.2B3i|7+3i]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 700/150 (CI Ara-C) {{#subobject:9934a6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 208: / Line 195: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3
 '''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 1120/120 (intermittent Ara-C) {{#subobject:1f1bb5|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 230: / Line 217: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 80 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 7
 *[[Daunorubicin (Cerubidine)]] 40 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3
 '''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #4, 1400/135 (CI Ara-C) {{#subobject:635ecb|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 294: / Line 281: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *CALGB 9222: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] versus multi-agent [[Regimen_classes#Chemotherapy|chemotherapy]] consolidation
 *HOVON 43 AML/SAKK 30/01: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] consolidation
 *ACCEDE: patients received a second course of the same regimen if their day 14 bone marrow was positive. Patients with PR or better at time of count recovery received allogeneic stem cell transplant if eligible, otherwise [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] if younger than 60 or [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] if greater than or equal to 60.
+</div></div>
 ===References===
 #Yates JW, Wallace HJ Jr, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973 Nov-Dec;57(4):485-8. [https://pubmed.ncbi.nlm.nih.gov/4586956 PubMed]
 #'''CALGB 7421:''' Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Bloomfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Ellison RR, Kung F, Henry P, McIntyre OR, Kaan SK. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood. 1981 Dec;58(6):1203-12. [http://www.bloodjournal.org/content/58/6/1203.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6946847 PubMed]
@@ Line 336: / Line 322: @@
 #'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047
 ##'''Subgroup analysis:''' Seymour JF, Döhner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017 Dec 14;17(1):852. [https://doi.org/10.1186/s12885-017-3803-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731212/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241450 PubMed]
 ==7+3d (intermediate-dose) {{#subobject:e82156|Regimen=1}}==
 +3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, CI Ara-C (100 mg/m<sup>2</sup>) {{#subobject:bb27bc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 404: / Line 389: @@
 |}
 ''Note: this was the upper bound of the allowable daunorubicin dose in AZA-AML-001.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 **Note: Dombret et al. 2015 did not specify which days the daunorubicin is administered; some protocols give daunorubicin on days 3 to 5
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *AML2003: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] versus [[#MAC.2FMAMAC.2FMAC_99|MAC/MAMAC/MAC]] consolidation
 *CALGB 10201: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation x 2
 *SWOG S0106: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation x 3
 *CLTR0310-301: [[#5.2B2d|5+2d]] consolidation
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, CI Ara-C (200 mg/m<sup>2</sup>) {{#subobject:cf53dd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 454: / Line 440: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3
 ====Supportive therapy====
 *"According to commonly accepted guidelines with no prophylactic IV antibiotics"
 *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients with only partial remission in both PALG studies underwent a second course with the same drugs, doses, and schedule.
 *PALG AML1/1999, non-responders: [[#CLAG|CLAG]] salvage
 *Patients in remission in both PALG studies: [[#HAM|HAM]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
 *ALFA-0701, CR or CRp: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation
+</div></div>
 ===References===
 #'''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://doi.org/10.1038/sj.leu.2403336 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14999298 PubMed]
 #'''LAM-2001:''' Chevallier P, Fornecker L, Lioure B, Béné MC, Pigneux A, Recher C, Witz B, Fegueux N, Bulabois CE, Daliphard S, Bouscary D, Vey N, Delain M, Bay JO, Turlure P, Bernard M, Himberlin C, Luquet I, Ifrah N, Harousseau JL; GOELAMS. Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial. Leukemia. 2010 Jul;24(7):1380-5. Epub 2010 May 27. [https://www.nature.com/articles/leu2010111 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20508614 PubMed]
@@ Line 495: / Line 478: @@
 #'''ECOG E2906:''' NCT02085408
 #'''ENHANCE-2:''' NCT04778397
 ==7+3d (high-dose) {{#subobject:9e2666|Regimen=1}}==
 +3d: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 700/270 {{#subobject:70583e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 520: / Line 502: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *JHOC-J1101: Patients with residual leukemia at day 14 underwent [[#5.2B2d_2|5+2d]] salvage
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 1400/240 {{#subobject:a33bec|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 545: / Line 528: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 1400/270 {{#subobject:664ec|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 579: / Line 562: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *HOVON 43 AML/SAKK 30/01: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|MiDAC]] consolidation
 *COSAH C-022, with CR, good- or intermediate-risk cytogenetics: [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
 *COSAH C-022, with CR, high-risk cytogenetics: [[#Cytarabine_.26_Etoposide_88|Cytarabine & etoposide]] consolidation
+</div></div>
 ===References===
 #'''ALFA 9000:''' Castaigne S, Chevret S, Archimbaud E, Fenaux P, Bordessoule D, Tilly H, de Revel T, Simon M, Dupriez B, Renoux M, Janvier M, Micléa JM, Thomas X, Bastard C, Preudhomme C, Bauters F, Degos L, Dombret H. Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood. 2004 Oct 15;104(8):2467-74. Epub 2004 May 13. [http://www.bloodjournal.org/content/104/8/2467.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15142880 PubMed]
 #'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377
@@ Line 600: / Line 582: @@
 #'''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709 PubMed] NCT01349972
 #'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846
 ==7+3d & GO {{#subobject:869f84|Regimen=1}}==
 +3d & GO: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of '''<u>d</u>'''aunorubicin, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, split GO dosing {{#subobject:4c0a05|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 619: / Line 600: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV over 2 hours once per day on days 1, 4, 7
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients in CR or CRp and platelet count at least 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine.2C_Daunorubicin.2C_Gemtuzumab_ozogamicin|Cytarabine, Daunorubicin, Gemtuzumab ozogamicin]] consolidation
 *Patients in CR or CRp and platelet count less than 100 x 10<sup>9</sup> by day 45 after the initiation of chemotherapy: [[#Cytarabine_.26_Daunorubicin|Cytarabine & Daunorubicin]] consolidation
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, single-day GO {{#subobject:4ug8f5|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 650: / Line 630: @@
 |}
 ''Note: this was a failed confirmatory study which led to the withdrawal of the FDA indication in 2010. The FDA indication was later reinstated in 2017.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 6 mg/m<sup>2</sup> IV over 2 hours once on day 4
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation x 3
+</div></div>
 ===References===
 #'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498
 ##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed]
 #'''SWOG S0106:''' Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. [http://www.bloodjournal.org/content/121/24/4854.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682338/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23591789 PubMed] NCT00085709
 ==7+3i {{#subobject:717935|Regimen=1}}==
 +3i: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>i</u>'''darubicin
 <br>AI: '''<u>A</u>'''ra-C (Cytarabine) & '''<u>I</u>'''darubicin
 <br>IA: '''<u>I</u>'''darubicin & '''<u>A</u>'''ra-C (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 80/12, intermittent Ara-C {{#subobject:bdc11c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 690: / Line 666: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 80 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 7
 *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 1 to 3
 '''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 100/12, CI Ara-C {{#subobject:c6cda|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 748: / Line 724: @@
 |-
 |}
+''Note: Patients in ECOG E3993 with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3
+'''7-day course (see note)'''
-'''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-''Patients in ECOG E3993 with persistent disease at day 14 (greater than 5% blasts) underwent an identical second cycle of 7+3i.''
 ===Regimen variant #3, 100/13, CI Ara-C {{#subobject:7f2eec|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 772: / Line 747: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Idarubicin (Idamycin)]] 13 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #4, 200/12, CI Ara-C {{#subobject:f33de6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 824: / Line 799: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>)
 *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3
 **Note: in HOVON/SAKK AML 29 & AML 42, idarubicin was given on days 5 to 7
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *HOVON/SAKK AML 29 & AML 42: [[#Amsacrine_.26_Cytarabine_88|Amsacrine & Cytarabine]]
 *ALFA-9801, patients achieiving CR: [[#Cytarabine_.26_Idarubicin_2|cytarabine & idarubicin]] consolidation
@@ Line 838: / Line 813: @@
 *COSAH C-022, patients achieving CR, high-risk cytogenetics: [[#CYVE|CYVE]] consolidation
 *HOVON/SAKK-132: [[#Daunorubicin_.26_IDAC|Daunorubicin & IDAC]] (remission induction cycle II)
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #5, with range {{#subobject:eb0168|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 854: / Line 830: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 to 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 to 1400 mg/m<sup>2</sup>)
 *[[Idarubicin (Idamycin)]] 9 to 12 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div></div>
 ===References===
 #Mandelli F, Petti MC, Ardia A, Di Pietro N, Di Raimondo F, Ganzina F, Falconi E, Geraci E, Ladogana S, Latagliata R, Malleo C, Nobile F, Petti N, Rotoli B, Specchia G, Tabilio A, Resegotti L; GIMEMA. A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia: a multicentric study from the Italian Co-operative Group GIMEMA. Eur J Cancer. 1991;27(6):750-5. [https://www.ejcancer.com/article/0277-5379(91)90181-C link to original article] [https://pubmed.ncbi.nlm.nih.gov/1829918 PubMed]
 #Wiernik PH, Banks PL, Case DC Jr, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weitberg AB. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood. 1992 Jan 15;79(2):313-9. [http://www.bloodjournal.org/content/79/2/313 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1730080 PubMed]
@@ Line 880: / Line 855: @@
 # '''HOVON/SAKK-132:''' Löwenberg B, Pabst T, Maertens J, Gradowska P, Biemond BJ, Spertini O, Vellenga E, Griskevicius L, Tick LW, Jongen-Lavrencic M, van Marwijk Kooy M, Vekemans MC, van der Velden WJFM, Beverloo B, Michaux L, Graux C, Deeren D, de Weerdt O, van Esser JWJ, Bargetzi M, Klein SK, Gadisseur A, Westerweel PE, Veelken H, Gregor M, Silzle T, van Lammeren-Venema D, Moors I, Breems DA, Hoogendoorn M, Legdeur MJC, Fischer T, Kuball J, Cornelissen J, Porkka K, Juliusson G, Meyer P, Höglund M, Gjertsen BT, Janssen JJWM, Huls G, Passweg J, Cloos J, Valk PJM, van Elssen CHMJ, Manz MG, Floisand Y, Ossenkoppele GJ. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood Adv. 2021 Feb 23;5(4):1110-1121. [https://doi.org/10.1182/bloodadvances.2020003855 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7903238/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33616652/ PubMed]
 # '''SWOG S1203:''' NCT01802333
 ==7+3i & Sorafenib {{#subobject:ab6409|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:567ab9|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 896: / Line 869: @@
 |}
 ''Note: Regimen details are from the phase 2 part of the published phase 1/2 trial.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] by the following age-based criteria:
 **60 and younger: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose: 6000 mg/m<sup>2</sup>)
 **Older than 60: 1500 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 4500 mg/m<sup>2</sup>)
 *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3
 ====Targeted therapy====
 *[[Sorafenib (Nexavar)]] 400 mg PO twice per day on days 1 to 7
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, idarubicin, sorafenib]] consolidation
+</div></div>
 ===References===
 <!-- no pre-pub disclosed -->
 #'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971
 ##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed]
 ==7+3d & Glasdegib {{#subobject:61520d|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:0e6b97|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 933: / Line 901: @@
 |}
 ''Note: glasdegib is continued beyond induction; see paper for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 ====Targeted therapy====
 *[[Glasdegib (Daurismo)]] 100 mg PO once per day, started on day -3
 '''28-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation
+</div></div>
 ===References===
 #'''B1371003:''' Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. Epub 2018 Sep 9. [https://doi.org/10.1002/ajh.25238 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30074259 PubMed] NCT01546038
 ==7+3m {{#subobject:240c72|Regimen=1}}==
 +3m: '''<u>7</u>''' days of cytarabine + '''<u>3</u>''' days of '''<u>m</u>'''itoxantrone
 <br>MAC: '''<u>M</u>'''itoxantrone & '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:7d87af|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 976: / Line 940: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients with persistent disease at day 14 (greater than 5% blasts): underwent an identical second cycle of [[#7.2B3m|7+3m]]
+</div></div>
 ===References===
 #Arlin Z, Case DC Jr, Moore J, Wiernik P, Feldman E, Saletan S, Desai P, Sia L, Cartwright K; Lederle Cooperative Group. Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Leukemia. 1990 Mar;4(3):177-83. [https://pubmed.ncbi.nlm.nih.gov/2179638 PubMed]
 #'''ECOG E3993:''' Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, Liesveld JL, Abboud CN, Dewald G, Hayes FA, Tallman MS, Wiernik PH; Eastern Cooperative Oncology. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004 Jan 15;103(2):479-85. Epub 2003 Sep 25. [http://www.bloodjournal.org/content/103/2/479.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14512295 PubMed] NCT04446052
 ==ADE (standard-dose Ara-C) {{#subobject:e221d7|Regimen=1}}==
 ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 <br>7-3-7: '''<u>7</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
 <br>8-3-5: '''<u>8</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 <br>10-3-5: '''<u>10</u>''' days of Cytarabine, '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 7-3-7, 700/150/525 {{#subobject:386fd2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,012: / Line 974: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7
 '''7-day course; can be repeated up to 3 times if CR not achieved'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *5-2-5 consolidation x 2
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 7-3-3, 700/180/300 {{#subobject:31dcd2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,038: / Line 1,001: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 7-3-3, 700/270/300 {{#subobject:3gh1d2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,061: / Line 1,024: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 90 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #4, 10-3-5, 1000/150/250, CI Ara-C {{#subobject:7ce6f9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,084: / Line 1,047: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 10 days, started on day 1 (total dose: 1000 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5
 *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''10-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #5, 10-3-5, 1025/150/500, CI Ara-C {{#subobject:7ce6f9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,107: / Line 1,070: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 25 mg/m<sup>2</sup>/day IV bolus once on day 1, then 100 mg/m<sup>2</sup>/day IV continuous infusion over 10 days (total dose: 1025 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''10-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #6, 8-3-5, 1600/150/500, intermittent Ara-C {{#subobject:f7e0ca|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,137: / Line 1,100: @@
 |}
 ''Note: these trials have complicated treatment schemas; see papers for details.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *UK MRC AML10: [[#ADE_.28standard-dose_Ara-C.29|ADE 10-3-5]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 8
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 '''8-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *UK MRC AML10: MACE consolidation
 *UK MRC AML15: Consolidation (see paper for details)
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #7, 10-3-5, 2000/150/500, intermittent Ara-C {{#subobject:77fe46|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,178: / Line 1,145: @@
 |}
 ''Note: these trials have complicated treatment schemas; see papers for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV every 12 hours on days 1 to 10
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''10-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#ADE_.28standard-dose_Ara-C.29|ADE 8-3-5]] re-induction
+</div></div>
 ===References===
 #Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8634416 PubMed]
 #'''UK MRC AML10:''' Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK; Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia: results of the Medical Research Council's 10th AML trial (MRC AML10). Blood. 1997 Apr 1;89(7):2311-8. [http://www.bloodjournal.org/content/89/7/2311.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9116274 PubMed]
@@ Line 1,206: / Line 1,172: @@
 <!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. -->
 #'''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.51.8571 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297940 PubMed] NCT00004128
 ==ADE (high-dose Ara-C) {{#subobject:c7eb71|Regimen=1}}==
 ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
 <br>HIDAC-3-5: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>5</u>''' days of Etoposide
 <br>HIDAC-3-7: '''<u>HI</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>3</u>''' days of Daunorubicin, '''<u>7</u>''' days of Etoposide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, HIDAC-3-5 {{#subobject:b1a101|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,227: / Line 1,192: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5, 7 (total dose: 24,000 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1, 3, 5
 *[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''7-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, HIDAC-3-7 {{#subobject:386df8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,250: / Line 1,215: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5, 7 (total dose per cycle: 24,000 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 1 to 7
 '''7-day course; can be repeated up to 3 times if CR not achieved'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *5-2-5 consolidation x 2
+</div></div>
 ===References===
 #Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996 Mar 1;87(5):1710-7. [http://www.bloodjournal.org/content/87/5/1710.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8634416 PubMed]
 <!-- Presented at the 53rd American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 10-13, 2011. -->
 #'''EORTC-GIMEMA AML-12:''' Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DL, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EW, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: Results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014 Jan 20;32(3):219-28. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.51.8571 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297940 PubMed] NCT00004128
 ==AIE {{#subobject:948b49|Regimen=1}}==
 AIE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>I</u>'''darubicin, '''<u>E</u>'''toposide
 <br>ICE: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c7b35a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,310: / Line 1,273: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 1 to 7 (total dose: 1400 mg/m<sup>2</sup>)
 *[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *ALLG M7: ICE versus IcE consolidation
 *NILG AML 02/06, early CR: IC consolidation
+</div></div>
 ===References===
 #'''ALLG M7:''' Bradstock KF, Matthews JP, Lowenthal RM, Baxter H, Catalano J, Brighton T, Gill D, Eliadis P, Joshua D, Cannell P, Schwarer AP, Durrant S, Gillett A, Koutts J, Taylor K, Bashford J, Arthur C, Enno A, Dunlop L, Szer J, Leahy M, Juneja S, Young GA; Australasian Leukaemia and Lymphoma Group. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood. 2005 Jan 15;105(2):481-8. Epub 2004 Jun 22. [http://www.bloodjournal.org/content/105/2/481.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15213095 PubMed]
 #Schlenk RF, Fröhling S, Hartmann F, Fischer JT, Glasmacher A, del Valle F, Grimminger W, Götze K, Waterhouse C, Schoch R, Pralle H, Mergenthaler HG, Hensel M, Koller E, Kirchen H, Preiss J, Salwender H, Biedermann HG, Kremers S, Griesinger F, Benner A, Addamo B, Döhner K, Haas R, Döhner H; AML Study Group Ulm. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004 Nov;18(11):1798-803. [https://www.nature.com/articles/2403528 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15385923 PubMed]
@@ Line 1,329: / Line 1,291: @@
 #'''CRIANT:''' de Witte T, Hagemeijer A, Suciu S, Belhabri A, Delforge M, Kobbe G, Selleslag D, Schouten HC, Ferrant A, Biersack H, Amadori S, Muus P, Jansen JH, Hellström-Lindberg E, Kovacsovics T, Wijermans P, Ossenkoppele G, Gratwohl A, Marie JP, Willemze R. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: final results of a prospective randomized European Intergroup Trial. Haematologica. 2010 Oct;95(10):1754-61. Epub 2010 May 21. [http://www.haematologica.org/content/95/10/1754.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20494931 PubMed] NCT00002926
 #'''NILG AML 02/06:''' Bassan R, Intermesoli T, Masciulli A, Pavoni C, Boschini C, Gianfaldoni G, Marmont F, Cavattoni I, Mattei D, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Ciceri F, Bernardi M, Scattolin AM, Todisco E, Campiotti L, Corradini P, Cortelezzi A, Ferrero D, Zanghì P, Oldani E, Spinelli O, Audisio E, Cortelazzo S, Bosi A, Falini B, Pogliani EM, Rambaldi A. Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML. Blood Adv. 2019 Apr 9;3(7):1103-1117. [http://www.bloodadvances.org/content/3/7/1103.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457212/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30948365 PubMed] NCT00495287
 ==CIA {{#subobject:de6dec|Regimen=1}}==
 CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 15/10/1000 {{#subobject:c6c8ec|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,348: / Line 1,309: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given 4 hours before cytarabine'''
 *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 '''5-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients not achieving CR or CRp: Optional second [[#CIA|CIA]] induction
 *Patients achieving CR or CRp: [[#CIA_2|CIA]] consolidation
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 20/10/1000 {{#subobject:4a7d81|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 1,371: / Line 1,333: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 ====Supportive therapy====
 *[[Levofloxacin (Levaquin)]]
 *[[Itraconazole (Sporanox)]]
 *[[Valacyclovir (Valtrex)]]
 *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] neither mandated nor forbidden and given per physician discretion
 '''5-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients with PR: a second course with the same drugs, doses, and schedule.
 *Patients achieving CR or CRi: [[#CIA_2|CIA]] consolidation
+</div></div>
 ===References===
 #Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. [https://doi.org/10.1002/ajh.23544/references long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23877926 PubMed]
 #'''MDACC 2010-0788:''' Jabbour E, Short NJ, Ravandi F, Huang X, Xiao L, Garcia-Manero G, Plunkett W, Gandhi V, Sasaki K, Pemmaraju N, Daver NG, Borthakur G, Jain N, Konopleva M, Estrov Z, Kadia TM, Wierda WG, DiNardo CD, Brandt M, O'Brien SM, Cortes JE, Kantarjian H. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer. 2017 Nov 15;123(22):4430-4439. Epub 2017 Jul 14. [https://doi.org/10.1002/cncr.30883 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739034/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28708931 PubMed] NCT01289457
 ==DA 3 + 10 {{#subobject:5c0062|Regimen=1}}==
 DA 3 + 10: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 50 mg/m<sup>2</sup> dauno {{#subobject:99321e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,420: / Line 1,378: @@
 |}
 ''Note: this regimen is very similar to [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3. Both trials have complicated treatment schemas; see papers for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 '''10-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *See papers for details (to be completed).
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 60 mg/m<sup>2</sup> dauno {{#subobject:211741|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,446: / Line 1,405: @@
 |}
 ''Note: this regimen is very similar to [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose; however, 1) there is slightly more cytarabine given, in an intermittent schedule, and 2) the daunorubicin is given intermittently over 5 days, not 3.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 '''10-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *CBF: [[#DA_3.2B8_.26_GO|DA 3+8 & GO]]
 *Non-CBF, no FLT3 mutation, not poor risk: [[#DA_3.2B8|DA 3+8]] versus DA 3+8 & Everolimus
 *Poor risk other than FLT3 mutation: Clofarabine & Daunorubicin versus [[#FLAG-Ida_2|FLAG-Ida]]
+</div></div>
 ===References===
 #'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 ## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
@@ Line 1,467: / Line 1,426: @@
 #'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535
 ##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed]
 ==DA 3 + 10, GO {{#subobject:e6f5bb|Regimen=1}}==
 DA 3 + 10, GO: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6a938e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,492: / Line 1,450: @@
 |-
 |}
-''Both trials have complicated treatment schemas; see papers for details.''
+''Note: Both trials have complicated treatment schemas; see papers for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 10
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1
 '''10-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *See paper for details (to be completed).
+</div></div>
 ===References===
 #'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 ## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
@@ Line 1,515: / Line 1,470: @@
 ##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed]
 ##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed]
 ==DAC {{#subobject:9b1553|Regimen=1}}==
 DAC: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''ladribine
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:f00b8a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,543: / Line 1,497: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3
 *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>)
 *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5
 ====Supportive therapy====
 *"According to commonly accepted guidelines with no prophylactic IV antibiotics"
 *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] recommended only for patients older than 50 years old whose leukemic blasts were negative for CD114 expression
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients with only partial remission in both studies underwent a second course with the same drugs, doses, and schedule.
 *Non-responders in PALG AML1/1999: [[#CLAG|CLAG]] salvage
 *Patients in remission in both studies: [[#HAM|HAM]], then [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
+</div></div>
 ===References===
 #'''PALG AML1/1999:''' Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, Skotnicki A, Jedrzejczak WW, Konopka L, Kuliczkowski K, Zdziarska B, Dmoszyńska A, Marianska B, Pluta A, Zawilska K, Komarnicki M, Kloczko J, Sulek K, Haus O, Stella-Holowiecka B, Baran W, Jakubas B, Paluszewska M, Wierzbowska A, Kielbinski M, Jagoda K; Polish Adult Leukemia Group. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia: multicenter, phase III study. Leukemia. 2004 May;18(5):989-97. [https://doi.org/10.1038/sj.leu.2403336 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14999298 PubMed]
 #'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed]
 ==FLAG-Ida {{#subobject:7fc219|Regimen=1}}==
 FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Lenograstim), '''<u>Ida</u>'''rubicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:44e85e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,585: / Line 1,535: @@
 |}
 ''<sup>1</sup>While this was a negative trial, a predefined analysis by cytogenetics showed a significant survival benefit for GO in patients with favorable cytogenetics.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 to 6
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 2 to 6, '''given 4 hours after fludarabine'''
 *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 4 to 6
 ====Growth factor therapy====
 *[[Lenograstim (Granocyte)]] 263 mcg SC once per day on days 1 to 7
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *See paper for details
+</div></div>
 ===References===
 #'''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
 ## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
 ##'''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
 ==HAA {{#subobject:0788e0|Regimen=1}}==
 HAA: '''<u>H</u>'''omoharringtonine (Omacetaxine), '''<u>A</u>'''ra-C (Cytarabine), '''<u>A</u>'''clarubicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:5c5c2e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,628: / Line 1,574: @@
 |}
 ''Note: There were significantly more deaths in this arm, despite a superior primary efficacy endpoint.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Omacetaxine (Synribo)]] 2 mg/m<sup>2</sup>/day (route not specified) on days 1 to 7
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 7
 *[[Aclarubicin (Aclacinon)]] 20 mg IV once per day on days 1 to 7
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patient in CR: [[#Intermediate-dose_Cytarabine_monotherapy_.28IDAC.29|IDAC]] consolidation x 2
+</div></div>
 ===References===
 #Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. Epub 2013 May 9. [https://doi.org/10.1016/S1470-2045(13)70152-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23664707 PubMed] ChiCTR-TRC-06000054
 ==ICL {{#subobject:a904d7|Regimen=1}}==
 ICL: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>L</u>'''omustine
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:909d7e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,658: / Line 1,604: @@
 | style="background-color:#91cf60" |Seems to have superior OS<br>OS24: 56% vs 48%<br>(HR 0.73, 95% CI 0.54-0.99)
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 5
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 *[[Lomustine (CCNU)]] 200 mg/m<sup>2</sup> PO once on day 1
 '''7-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[Acute_myeloid_leukemia#IC_.26_Norethandrolone|IC and methotrexate/mercaptopurine with norethandrolone]]
+</div></div>
 ===References===
 #'''LAM-SA 2007:''' Pigneux A, Béné MC, Salmi LR, Dumas PY, Delaunay J, Bonmati C, Guièze R, Luquet I, Cornillet-Lefebvre P, Delabesse E, Ianotto JC, Ojeda-Uribe M, Hunault M, Banos A, Fornecker LM, Bernard M, Jourdan E, Vey N, Zerazhi H, Hishri Y, Mineur A, Asselineau J, Delepine R, Cahn JY, Ifrah N, Récher C; French Innovative Leukemia Organization. Improved survival by adding lomustine to conventional chemotherapy for elderly patients with aml without unfavorable cytogenetics: results of the LAM-SA 2007 FILO trial. J Clin Oncol. 2018 36:32, 3203-3210. Epub 2018 Sep 27. [https://doi.org/10.1200/JCO.2018.78.7366 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30260758 PubMed] NCT00590837
 ==MEC {{#subobject:324735|Regimen=1}}==
 MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine
 <br>MICE: '''<u>MI</u>'''toxantrone, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide
 <br>MAE: '''<u>M</u>'''itoxantrone, '''<u>A</u>'''ra-C (Cytarabine), '''<u>E</u>'''toposide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:33e408|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,699: / Line 1,643: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mitoxantrone (Novantrone)]] 7 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 700 mg/m<sup>2</sup>)
 '''7-day course'''
+</div></div>
 ===References===
 #'''EORTC/GIMEMA AML-13:''' Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, Muus P, Lefrère F, Berneman Z, Fillet G, Denzlinger C, Willemze R, Leoni P, Leone G, Casini M, Ricciuti F, Vignetti M, Beeldens F, Mandelli F, De Witte T; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood. 2005 Jul 1;106(1):27-34. Epub 2005 Mar 10. [http://www.bloodjournal.org/content/106/1/27.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895135/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15761020 PubMed] NCT00002719
 ##'''Update:''' Jehn U, Suciu S, Thomas X, Lefrère F, Muus P, Berneman Z, Marie JP, Adamo F, Fillet G, Nobile F, Ricciuti F, Leone G, Rizzoli V, Montanaro M, Beeldens F, Fazi P, Mandelli F, Willemze R, de Witte T, Amadori S. Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial. Leukemia. 2006 Oct;20(10):1723-30. Epub 2006 Aug 17. [https://www.nature.com/articles/2404356 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16932345 PubMed]
 #'''EORTC/GIMEMA AML-17:''' Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, De Fabritiis P, Venditti A, Ho AD, Lübbert M, Thomas X, Latagliata R, Halkes CJ, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013 Dec 10;31(35):4424-30. Epub 2013 Oct 14. [https://doi.org/10.1200/JCO.2013.49.0771 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24127442 PubMed] NCT00052299
 =Subsequent induction therapy, standard and older "fit" patients=
 ''Note: these are aggressive remission induction regimens given with curative intent, as part of a pre-planned protocol of therapy. They are less common in adults in the United States, but are often called "Course 2" or similar in other countries. These are to be distinguished from salvage therapy, which is outline below.''
 ==DA 3+8 {{#subobject:5c6662|Regimen=1}}==
 DA 3+8: '''<u>D</u>'''aunorubicin & '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 10</u>''' days of cytarabine
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:aq1641|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,734: / Line 1,674: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Non-core-binding factor (CBF) AML, no FLT3 mutation, and not poor risk
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#DA_3_.2B_10|DA 3+10]] versus [[#DA_3_.2B_10|DA 3+10]]; high-dose
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 8
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 '''10-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 1 versus [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 2
+</div></div>
 ===References===
 #'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535
 ##'''Update:''' Burnett AK, Das Gupta E, Knapper S, Khwaja A, Sweeney M, Kjeldsen L, Hawkins T, Betteridge SE, Cahalin P, Clark RE, Hills RK, Russell NH; UK NCRI AML Study Group. Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial. Haematologica. 2018 Oct;103(10):1654-1661. Epub 2018 Jul 5. [https://doi.org/10.3324/haematol.2018.189514 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165825/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29976746 PubMed]
 ==DA 3+8 & GO {{#subobject:6yy4bz|Regimen=1}}==
 DA 3+8 & GO: '''<u>D</u>'''aunorubicin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>3</u>''' days of daunorubicin '''<u>+ 8</u>''' days of cytarabine, '''<u>G</u>'''emtuzumab '''<u>O</u>'''zogamicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6a51fv|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 1,765: / Line 1,709: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Core-binding factor (CBF) AML
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#DA_3_.2B_10|DA 3+10]] versus [[#DA_3_.2B_10|DA 3+10]]; high-dose
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 1 to 8
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 1
 '''8-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 1 versus [[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] x 2
+</div></div>
 ===References===
 #'''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Kell J, Cavenagh J, Kjeldsen L, McMullin MF, Cahalin P, Dennis M, Friis L, Thomas IF, Milligan D, Clark RE; UK NCRI AML Study Group. A randomized comparison of daunorubicin 90 mg/m<sup>2</sup> vs 60 mg/m<sup>2</sup> in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015 Jun 18;125(25):3878-85. Epub 2015 Apr 1. [https://doi.org/10.1182/blood-2015-01-623447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25833957 PubMed] ISRCTN55675535
@@ Line 1,789: / Line 1,736: @@
 ''Note: these regimens are generally considered to be part of a non-curative line of treatment.''
 ==Azacitidine monotherapy {{#subobject:791718|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:7509ab|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,824: / Line 1,771: @@
 |}
 ''Note: Patients in AZA PH GL 2003 had 20-30% blasts in the bone marrow.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7
 '''28-day cycle for at least 6 cycles'''
+</div></div>
 ===References===
 #'''AZA PH GL 2003:''' Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. Epub 2009 Dec 21. [https://doi.org/10.1200/JCO.2009.23.8329 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20026804 PubMed] NCT00071799
 #'''AZA-AML-001:''' Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal Del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. Epub 2015 May 18. [http://www.bloodjournal.org/content/126/3/291.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504945/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25987659 PubMed] NCT01074047
@@ Line 1,839: / Line 1,784: @@
 # '''PEVOLAM:''' NCT04090736
 # '''PRAN-16-52:''' NCT03151408
 ==Azacitidine & Venetoclax {{#subobject:73ce92|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:1ea50d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,863: / Line 1,807: @@
 |-
 |}
-''Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.''
+''Note: Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 ====Targeted therapy====
 *[[Venetoclax (Venclexta)]] as follows:
 **Cycle 1: 20 mg PO once on day 2, then 50 mg PO once on day 3, then 100 mg PO once on day 4, then 200 mg PO once on day 5, then 400 mg PO once per day on days 6 to 28
 **Cycle 2 onwards: 400 mg PO once per day
 '''28-day cycles'''
+</div></div>
 ===References===
 #'''M14-358:''' DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. [https://doi.org/10.1016/s1470-2045(18)30010-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29339097 PubMed] [https://clinicaltrials.gov/ct2/show/NCT02203773 NCT02203773]
 ##'''Update:''' DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. [https://doi.org/10.1182/blood-2018-08-868752 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6318429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30361262 PubMed]
 #'''VIALE-A:''' DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. [https://doi.org/10.1056/nejmoa2012971 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32786187 PubMed] NCT02993523
 #'''ENHANCE-2:''' NCT04778397
 ==Azacitidine & Gemtuzumab ozogamicin {{#subobject:6f77be|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:188f5c|Variant=1}}===
+===Protocol {{#subobject:188f5c|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
@@ Line 1,901: / Line 1,839: @@
 |-
 |}
+''Note: Patients with WBC greater than 10 x 10<sup>9</sup>/L at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC greater than x 10<sup>9</sup>/L. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.''
-''Patients with WBC greater than 10 x 10<sup>9</sup>/L at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC greater than x 10<sup>9</sup>/L. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Supportive therapy, pre-treatment phase====
 *[[Hydroxyurea (Hydrea)]] 1500 mg PO twice per day or in higher doses if necessary
 ''Once WBC is less than 10 x 10<sup>9</sup>/L, stop Hydrea and proceed:''
 ====Chemotherapy====
 *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8
 ====Supportive therapy====
 *"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]]
 '''8-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *If D14 bone marrow with 5% or more blasts, a second induction cycle identical to the first was administered
 *Patients achieving CR or CRi: [[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine and gemtuzumab ozogamicin]] consolidation, within 60 days
+</div></div>
 ===References===
 #Nand S, Godwin J, Smith S, Barton K, Michaelis L, Alkan S, Veerappan R, Rychlik K, Germano E, Stiff P. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Leuk Lymphoma. 2008 Nov;49(11):2141-7. [https://doi.org/10.1080/10428190802451254 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19021057 PubMed]
 <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
 #'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814
 ==Clofarabine monotherapy {{#subobject:18ac50|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 20 mg/m<sup>2</sup> {{#subobject:42be8e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,952: / Line 1,879: @@
 |}
 ''<sup>1</sup>Reported efficacy is based on the 2013 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''4- to 6-week cycle for 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 30 mg/m<sup>2</sup> {{#subobject:f9ef00|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 1,985: / Line 1,912: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''5-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *A second induction was permitted for SD or better.
 *MDACC 2004-0183: Responders proceeded to clofarabine & cytarabine consolidation
+</div></div>
 ===References===
 #'''MDACC 2004-0183:''' Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565853 PubMed] NCT00088218
 #'''UWCM-001; BIOV-121:''' Burnett AK, Russell NH, Kell J, Dennis M, Milligan D, Paolini S, Yin J, Culligan D, Johnston P, Murphy J, McMullin MF, Hunter A, Das-Gupta E, Clark R, Carr R, Hills RK. European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy. J Clin Oncol. 2010 May 10;28(14):2389-95. Epub 2010 Apr 12. [https://doi.org/10.1200/JCO.2009.26.4242 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20385984 PubMed]
@@ Line 2,002: / Line 1,928: @@
 ##'''Update:''' Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK; UK National Cancer Research Institute AML Working Group. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013 Aug 22;122(8):1384-94. Epub 2013 Jul 9. [http://www.bloodjournal.org/content/122/8/1384.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23838349 PubMed]
 ##'''Update:''' Burnett AK, Russell NH, Hills RK, Kell J, Nielsen OJ, Dennis M, Cahalin P, Pocock C, Ali S, Burns S, Freeman S, Milligan D, Clark RE. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia. 2017 Feb;31(2):310-317. Epub 2016 Sep 2. [https://doi.org/10.1038/leu.2016.225 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27624670 PubMed]
 ==Clofarabine & LoDAC {{#subobject:7a3edd|Regimen=1}}==
 Clofarabine & LoDAC: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1 {{#subobject:12351c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,021: / Line 1,946: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first'''
 *[[Cytarabine (Ara-C)]] 20 mg SC once per day on days 1 to 14, '''given 4 hours after clofarabine on days 1 to 5'''
 '''28- to 49-day cycle for up to 2 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *CRi or better: [[#Clofarabine_.26_LoDAC_2|Clofarabine & LoDAC]] consolidation
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2 {{#subobject:7d207f|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,042: / Line 1,968: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 *[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10
 '''10-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients not achieving CR: Optional identical [[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]] re-induction after at least 28 days
 **Patients not achieving CR after the second induction: [[#Decitabine_monotherapy_3|Decitabine]] salvage
 *Patients achieving CR: [[#Clofarabine_.26_LoDAC.2FDecitabine|Clofarabine & low-dose cytarabine alternating with decitabine]] consolidation
+</div></div>
 ===References===
 #'''MDACC 2004-0183:''' Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008 Sep 1;112(5):1638-45. Epub 2008 Jun 18. [http://www.bloodjournal.org/content/112/5/1638.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081352/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565853 PubMed] NCT00088218
 #Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://doi.org/10.1002/cncr.27429 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22282348 PubMed]
 ##'''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://doi.org/10.1002/cncr.29367 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25809968 PubMed]
 ==CPX-351 monotherapy {{#subobject:03f404|Regimen=1}}==
 CPX-351: Liposomal Cytarabine and Daunorubicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:0b4cdf|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,085: / Line 2,009: @@
 |}
 ''<sup>1</sup>Reported efficacy is based on the 2021 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine and daunorubicin liposomal (Vyxeos)|CPX-351 (Vyxeos)]] as follows:
 **First induction: 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1, 3, 5
 **Second induction (if needed): 100 units/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 3
 '''One or two courses'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *CR/CRi: [[#CPX-351_monotherapy_2|CPX-351]] consolidation
+</div></div>
 ===References===
 <!-- Presented in part in abstract form at the 52nd annual meeting of the American Society of Hematology, Orlando, FL December 4-7, 2010. -->
 #'''CLTR0308-204:''' Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, Solomon SR, Kolitz JE, Cooper M, Yeager AM, Louie AC, Feldman EJ. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014 May 22;123(21):3239-46. Epub 2014 Mar 31. [http://www.bloodjournal.org/content/123/21/3239.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624448/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24687088 PubMed] NCT00788892
 <!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
 #'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084
 ##'''Update:''' Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. [https://doi.org/10.1016/s2352-3026(21)00134-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34171279/ PubMed]
 ==Decitabine monotherapy {{#subobject:2d1dad|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1 {{#subobject:b60a91|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,122: / Line 2,043: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''4- to 6-week cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2 {{#subobject:22a24e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,155: / Line 2,076: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 ====Supportive therapy====
 *[[Hydroxyurea (Hydrea)]] (dose not specified) could be used up until cycle 1 day 15
 '''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3 {{#subobject:c6ffdd|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,180: / Line 2,099: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 10
 ====Supportive therapy====
 *[[Hydroxyurea (Hydrea)]] (dose not specified) allowed during and prior to cycle 1
 '''28-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *OSU 07017, persistent AML (greater than or equal to 5% blasts): repeated cycles with 10 days of decitabine as described above
 *OSU 07017, no morphologic evidence of AML (less than 5% blasts): received 5 days of decitabine as described by [[#Decitabine_monotherapy_2|decitabine]] maintenance
+</div></div>
 ===References===
 #'''OSU 07017:''' Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368434 PubMed] NCT00492401
 <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. -->
@@ Line 2,204: / Line 2,120: @@
 #'''JNJ AML-2002:''' Montesinos P, Roboz GJ, Bulabois CE, Subklewe M, Platzbecker U, Ofran Y, Papayannidis C, Wierzbowska A, Shin HJ, Doronin V, Deneberg S, Yeh SP, Ozcan MA, Knapper S, Cortes J, Pollyea DA, Ossenkoppele G, Giralt S, Döhner H, Heuser M, Xiu L, Singh I, Huang F, Larsen JS, Wei AH. Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study. Leukemia. 2021 Jan;35(1):62-74. Epub 2020 Mar 16. [https://doi.org/10.1038/s41375-020-0773-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7787975/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32203138 PubMed] NCT02472145
 #'''SEAMLESS:''' Kantarjian HM, Begna KH, Altman JK, Goldberg SL, Sekeres MA, Strickland SA, Arellano ML, Claxton DF, Baer MR, Gautier M, Berman E, Seiter K, Solomon SR, Schiller GJ, Luger SM, Butrym A, Gaidano G, Thomas XG, Montesinos P, Rizzieri DA, Quick DP, Venugopal P, Gaur R, Maness LJ, Kadia TM, Ravandi F, Buyse ME, Chiao JH. Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS). Cancer. 2021 Dec 1;127(23):4421-4431. Epub 2021 Aug 23. [https://doi.org/10.1002/cncr.33828 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34424530/ PubMed] NCT01303796
 ==Decitabine & Venetoclax {{#subobject:30c499|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 5 days of decitabine {{#subobject:2aab30|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,218: / Line 2,133: @@
 |-
 |}
+''Note: Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.''
-''Patients with WBC greater than 25 x 10<sup>9</sup>/L at presentation were pre-treated with hydroxyurea or leukapheresis.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV or SC once per day on days 1 to 5
 ====Targeted therapy====
 *[[Venetoclax (Venclexta)]] 400, 800, or 1200 mg PO once per day
 '''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 10 days of decitabine {{#subobject:08cde2|Variant=2}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,242: / Line 2,153: @@
 |-
 |}
+''Note: Therapy with hydroxyurea or one dose of cytarabine up to 2000 mg/m<sup>2</sup> was allowed during cycle 1.''
-''Therapy with hydroxyurea or one dose of cytarabine up to 2000 mg/m<sup>2</sup> was allowed during cycle 1.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV or SC once per day on days 1 to 10
 ====Targeted therapy====
 *[[Venetoclax (Venclexta)]] as follows:
 **Cycle 1: 400 mg PO once per day
 **Cycle 2 onwards: 400 mg PO once per day on days 1 to 21
 '''28-day cycles'''
+</div></div>
 ===References===
 #'''M14-358:''' DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb;19(2):216-228. [https://doi.org/10.1016/s1470-2045(18)30010-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29339097 PubMed] [https://clinicaltrials.gov/ct2/show/NCT02203773 NCT02203773]
 ##'''Update:''' DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. Epub 2018 Oct 25. [https://doi.org/10.1182/blood-2018-08-868752 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6318429/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30361262 PubMed]
 <!-- #'''Abstract:''' Maiti A, DiNardo CD, Cortes JE, Borthakur G, Pemmaraju,N, Benton CB, Kadia TM, Takahashi K, Naqvi K, Ravandi F, Alvarado Y, Short NJ, Daver NG, Sasaki K, Ohanian MN, Garcia-Manero G, Thompson PA, Kornblau SM, Masarova L, Jain N, Jabbour EJ, Andreeff M, Maduike R, Guerrero JA, Zhang Q, Cavazos A, Ma H, Rausch CR, Bivins CA, Vaughan K, Pierce SA, Ning J, Qiao W, Welch JS, Kantarjian HM,  Konopleva MY. Interim Analysis of Phase II Study of Venetoclax with 10-Day Decitabine (DEC10-VEN) in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Blood, 132(Suppl 1), 286. [http://www.bloodjournal.org/content/132/Suppl_1/286 link to original abstract] [https://clinicaltrials.gov/ct2/show/NCT03404193 NCT03404193] -->
 #'''DEC10-VEN:''' DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020 Oct;7(10):e724-e736. Epub 2020 Sep 5. [https://doi.org/10.1016/s2352-3026(20)30210-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7549397/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32896301 PubMed] NCT03404193
 ==Gemtuzumab ozogamicin monotherapy {{#subobject:4e3c9a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e01685|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,281: / Line 2,185: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 6 mg/m<sup>2</sup> IV once on day 1, then 3 mg/m<sup>2</sup> IV once on day 8
 '''8-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients with benefit: [[#Gemtuzumab_ozogamicin_monotherapy_2|Gemtuzumab ozogamicin]] maintenance
+</div></div>
 ===References===
 <!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
 #'''EORTC/GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [https://doi.org/10.1200/jco.2015.64.0060 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26811524 PubMed] NCT00091234
 ==Glasdegib & LoDAC {{#subobject:ba44c2|Regimen=1}}==
 Glasdegib & LoDAC: Glasdegib & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e4c7c9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,314: / Line 2,216: @@
 |}
 ''<sup>1</sup>Reported efficacy is based on the 2021 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10
 ====Targeted therapy====
 *[[Glasdegib (Daurismo)]] 100 mg PO once per day
 '''28-day cycles'''
+</div></div>
 ===References===
 <!-- # '''Abstract:''' Cortes JE, Heidel FH, Heuser M, Fiedler W, Smith BD, Robak T. Montesinos Fernandez P, Ma WW, Shaik MN, Zeremski M, O'Connell A,  Chan, G. A Phase 2 Randomized Study of Low Dose Ara-C with or without Glasdegib (PF-04449913) in Untreated Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome. Blood 2016, 128(22), 99. [http://www.bloodjournal.org/content/128/22/99 link to original article] '''contains dosing details in manuscript''' -->
 #'''BRIGHT AML 1003:''' Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. Epub 2018 Dec 16. [https://www.nature.com/articles/s41375-018-0312-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365492/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30555165 PubMed] NCT01546038
 ##'''Update:''' Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Pérez-Simón JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. Epub 2021 Mar 19. Erratum in: Ann Hematol. 2021 Jul;100(7):1917-1918. [https://doi.org/10.1007/s00277-021-04465-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8043884/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33740113/ PubMed]
 ==Low-dose Cytarabine monotherapy (LoDAC) {{#subobject:25e1c6|Regimen=1}}==
 LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 <br>LDAC: '''<u>L</u>'''ow-dose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 20 mg twice per day, indefinite duration {{#subobject:a3d4fb|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,360: / Line 2,258: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 20 mg SC twice per day on days 1 to 10
 '''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 20 mg/m<sup>2</sup> twice per day, limited duration {{#subobject:d5c6f7|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,409: / Line 2,307: @@
 |}
 ''<sup>1</sup>Reported efficacy for UK NCRI AML16 is based on the 2016 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC twice per day on days 1 to 10
 '''4- to 6-week cycle for up to 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 20 mg/m<sup>2</sup> once per day, indefinite duration {{#subobject:fd61d0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,437: / Line 2,335: @@
 |}
 ''<sup>1</sup>Reported efficacy for VIALE-C is based on an unplanned follow-up analysis described in the initial paper.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10
 '''28-day cycles'''
+</div></div>
 ===References===
 <!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. -->
 #'''DACO-016:''' Kantarjian HM, Thomas XG, Dmoszyńska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. Epub 2012 Jun 11. [https://doi.org/10.1200/jco.2011.38.9429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874148/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22689805 PubMed] NCT00260832
 ##'''Subgroup analysis:''' Wierzbowska A, Wawrzyniak E, Pluta A, Robak T, Mazur GJ, Dmoszynska A, Cermak J, Oriol A, Lysak D, Arthur C, Doyle M, Xiu L, Ravandi F, Kantarjian HM. Decitabine improves response rate and prolongs progression-free survival in older patients with newly diagnosed acute myeloid leukemia and with monosomal karyotype: a subgroup analysis of the DACO-016 trial. Am J Hematol. 2018 May;93(5):E125-E127. Epub 2018 Feb 24. [https://doi.org/full/10.1002/ajh.25062 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29417613 PubMed]
@@ Line 2,463: / Line 2,359: @@
 ##'''Update:''' Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. [https://doi.org/10.1038/s41408-021-00555-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34599139/ PubMed]
 #'''POLO-AML-2:''' NCT01721876
 ==LoDAC & Venetoclax {{#subobject:b84441|Regimen=1}}==
 LoDAC & Venetoclax: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & Venetoclax
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e84ab4|Variant=1}}===
 {| class="wikitable" style="width: 100%; text-align:center;"
@@ Line 2,488: / Line 2,383: @@
 |-
 |}
-''<sup>1</sup>Reported efficacy for VIALE-C is based on the 2021 update.''<br>
+''<sup>1</sup>Reported efficacy for VIALE-C is based on the 2021 update.''
-''The dose of venetoclax in M14-387 was reduced by 50% for moderate CYP3A inhibitors and approximately 75% to 90% for strong inhibitors.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 10
 ====Targeted therapy====
 *[[Venetoclax (Venclexta)]] as follows:
 **Cycle 1: 100 mg PO once on day 1, then 200 mg PO once on day 2, then 400 mg PO once on day 3, then 600 mg PO once per day on days 4 to 28
 **Cycle 2 onwards: 600 mg PO once per day
 '''28-day cycles'''
+====Dose modifications====
+*M14-387: The dose of venetoclax was reduced by 50% for moderate CYP3A inhibitors and approximately 75% to 90% for strong inhibitors.
+</div></div>
 ===References===
 #'''M14-387:''' Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019 May 20;37(15):1277-1284. Epub 2019 Mar 20. [https://doi.org/10.1200/JCO.18.01600 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524989/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30892988 PubMed] NCT02287233
 #'''VIALE-C:''' Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. [https://doi.org/10.1182/blood.2020004856 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7290090/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32219442 PubMed] NCT03069352
 ##'''Update:''' Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. Erratum in: Blood Cancer J. 2021 Oct 26;11(10):171. [https://doi.org/10.1038/s41408-021-00555-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8486817/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34599139/ PubMed]
 ==Temozolomide monotherapy {{#subobject:261bcb|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:fb4aeb|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,522: / Line 2,412: @@
 |-
 |}
+''Note: Patient selection was based on MGMT expression by Western blot. See article for details.''
-''Patient selection was based on MGMT expression by Western blot. See article for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup>/day PO on days 1 to 7
 **Complete responders could receive: 200 mg/m<sup>2</sup>/day PO on days 1 to 5
 '''28-day cycle for up to 12 cycles'''
+</div></div>
 ===References===
 #Brandwein JM, Kassis J, Leber B, Hogge D, Howson-Jan K, Minden MD, Galarneau A, Pouliot JF. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression. Br J Haematol. 2014 Dec;167(5):664-70. Epub 2014 Aug 27. [https://doi.org/10.1111/bjh.13094 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25160658 PubMed]
 =Consolidation after upfront therapy=
 ==5+2d {{#subobject:b409f7|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a67da7|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,549: / Line 2,435: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 '''5-day course'''
+</div></div>
 ===References===
 <!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
 #'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084
 ==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:caa3a2|Regimen=1}}==
 HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 <br>HDAC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 <br>HDAraC: '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>AraC</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 2000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:4e73ae|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,582: / Line 2,465: @@
 |}
 ''Details in the text are scant.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Cytarabine_.26_Mitoxantrone_.28MC.29|Cytarabine & Mitoxantrone]] consolidation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1, 3, 5 (total dose: 12,000 mg/m<sup>2</sup>)
 '''5-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 2 cycles of 2000 mg/m<sup>2</sup> every 12 hours x 10 {{#subobject:2a4b32|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,609: / Line 2,493: @@
 |}
 ''Note: length of cycle was not specified in the manuscript; 28-day cycle is typical for this regimen.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#BHAC-MMV_88|BHAC-MMV]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 20,000 mg/m<sup>2</sup>)
 '''28-day cycle for 2 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *A-VVV
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 1 cycle of 3000 mg/m<sup>2</sup> every 12 hours x 12 {{#subobject:a0e7d9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,637: / Line 2,522: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#5.2B2i_88|5+2i]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 6 (total dose: 36,000 mg/m<sup>2</sup>)
 '''6-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #4, 3 cycles of 3000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:746f61|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,693: / Line 2,578: @@
 |}
 ''Note: CALGB 9222 specified that each cycle begins within 2 weeks after hematopoietic recovery from the preceding cycle. SORAML specified a 28-day (minimum) cycle or 1 week after marrow recovery, whichever comes later.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *CALGB 9222: [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
 *SWOG S0106: [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose versus [[#7.2B3d_.26_GO|7+3d & GO]]
@@ Line 2,701: / Line 2,586: @@
 *SORAML: [[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose versus [[#7.2B3d_.26_Sorafenib_99|7+3d & Sorafenib]]
 *COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 '''3 cycles of varying durations'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *SWOG S0106: GO maintenance versus [[Acute_myeloid_leukemia_-_null_regimens#Observation|no further treatment]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #5, 3 cycles of 2000 mg/m<sup>2</sup> every 12 hours x 10 {{#subobject:8887b8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,727: / Line 2,613: @@
 |}
 ''Note: this was considered an experimental arm in Japan, given the timing of HiDAC approval. Reported efficacy is based on the 2010 update by Miyawaki et al.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B5d_88|7+5d]] or [[#7.2B3i|7+3i]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 5 (total dose per cycle: 10,000 mg/m<sup>2</sup>)
 '''3 cycles, started 1 week after neutrophils, WBCs, and platelets recovered to more than 1500/uL, 3 × 10<sup>9</sup>/L, and 100 × 10<sup>9</sup>/L'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #6, 4 cycles of 3000 mg/m<sup>2</sup> every 12 hours x 6 {{#subobject:0c2779|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,765: / Line 2,651: @@
 |}
 ''Note: cycle length of HiDAC is not specified; 28-day cycle is often used in clinical practice.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *ALFA-9802: Timed sequential therapy +/- GM-CSF priming
 *COSAH C-022: [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 '''28-day cycle for up to 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *ALFA-9802: Cytarabine & Daunorubicin maintenance
+</div></div>
 ===References===
 #'''CALGB 8525:''' Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd; [[Study_Groups#CALGB|CALGB]]. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994 Oct 6;331(14):896-903. [https://doi.org/10.1056/NEJM199410063311402 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8078551 PubMed]
 #Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, Wiernik PH. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998 Dec 3;339(23):1649-56. [https://doi.org/10.1056/NEJM199812033392301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9834301 PubMed]
@@ Line 2,794: / Line 2,679: @@
 #'''SORAML:''' Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Krämer A, Schäfer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hänel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanß C, Repp R, Heits F, Dürk H, Hase J, Klut IM, Illmer T, Bornhäuser M, Schaich M, Parmentier S, Görner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. Epub 2015 Nov 6. [https://doi.org/10.1016/S1470-2045(15)00362-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26549589 PubMed] NCT00893373
 #'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846
 ==Intermediate-dose Cytarabine monotherapy (IDAC) {{#subobject:f5cd74|Regimen=1}}==
 IDAC: '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 <br>mIDAC: '''<u>m</u>'''odified '''<u>I</u>'''ntermediate '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 1000 mg/m<sup>2</sup> x 3 {{#subobject:0340ec|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,811: / Line 2,694: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Stub#Amonafide_.26_Cytarabine|Amonafide & Cytarabine]] versus [[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 3, 5 (total dose per cycle: 3000 mg/m<sup>2</sup>)
 '''3 cycles (length not specified)'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 1000 mg/m<sup>2</sup> x 10 {{#subobject:cbba35|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,839: / Line 2,722: @@
 |}
 ''Note: cycle length was not specified; 28-day cycles are frequently used in this setting.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#BHAC-MMV_88|BHAC-MMV]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days 1 to 5 (total dose: 10,000 mg/m<sup>2</sup>)
 '''28-day cycle for 2 cycles (see note)'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *A-VVV
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 1000 mg/m<sup>2</sup> x 12 {{#subobject:22eda3|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
@@ Line 2,863: / Line 2,747: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3d_.28standard-dose.29|7+3d]]; standard-dose versus [[#7.2B3d_.28high-dose.29|7+3d]]; high-dose
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours every 12 hours on days 1 to 6 (total dose: 12,000 mg/m<sup>2</sup>)
 '''6-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Transplant eligible patients: [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]]
 *Transplant ineligible patients: Gemtuzumab ozogamicin maintenance versus [[Acute_myeloid_leukemia_-_null_regimens#Observation|no further treatment]]
+</div></div>
 ===References===
 #'''HOVON 43 AML/SAKK 30/01:''' Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G; HOVON; AMLSG; SAKK. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. Erratum in: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. [https://doi.org/10.1056/NEJMoa0901409 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19776405 PubMed] ISRCTN77039377
 #Fukushima T, Urasaki Y, Yamaguchi M, Ueda M, Morinaga K, Haba T, Sugiyama T, Nakao S, Origasa H, Umehara H, Ueda T. A randomized comparison of modified intermediate-dose Ara-C versus high-dose ara-c in post-remission therapy for acute myeloid leukemia. Anticancer Res. 2012 Feb;32(2):643-7. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22287757 PubMed]
 #'''ACCEDE:''' Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B. Phase III open-label randomized study of cytarabine in combination with amonafide l-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015 Apr 10;33(11):1252-7. Epub 2015 Mar 2. [https://doi.org/10.1200/jco.2014.57.0952 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732165 PubMed] NCT00715637
 ==HiDAC & G-CSF {{#subobject:e0396d|Regimen=1}}==
 HiDAC & G-CSF: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) & '''<u>G</u>'''ranulocyte '''<u>C</u>'''olony '''<u>S</u>'''timulating '''<u>F</u>'''actor
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:d8edc4|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 2,902: / Line 2,783: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Cytarabine.2C_Daunorubicin.2C_G-CSF_88|Cytarabine, Daunorubicin, G-CSF]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1, 3, 5 (total dose per cycle: 18,000 mg/m<sup>2</sup>)
 ====Growth factor therapy====
 *[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 5
 '''35-day cycle for 3 cycles'''
+</div></div>
 ===References===
 #'''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [https://doi.org/10.1200/JCO.2016.70.4551 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28221862 PubMed] NCT00932412
 ==Azacitidine monotherapy {{#subobject:7abfd6|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:f7e3f6|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,933: / Line 2,809: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Azacitidine_.26_Gemtuzumab_ozogamicin_2|Azacitidine & Gemtuzumab ozogamicin]] consolidation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once on day 1
 '''28-day cycle for 4 cycles'''
+</div></div>
 ===References===
 <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
 #'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814
 ==Azacitidine & Gemtuzumab ozogamicin {{#subobject:e5ff95|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:eb3f69|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 2,961: / Line 2,834: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Azacitidine_.26_Gemtuzumab_ozogamicin|Azacitidine & Gemtuzumab ozogamicin]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 7
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once on day 8
 ====Supportive therapy====
 *"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]]
 *Growth factors per physician discretion
 '''8-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#Azacitidine_monotherapy_2|Azacitidine]] maintenance, within 42 days of completion of consolidation
+</div></div>
 ===References===
 <!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
 #'''SWOG S0703:''' Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://www.bloodjournal.org/content/122/20/3432.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24092933 PubMed] NCT00658814
 ==BuCy, then auto HSCT {{#subobject:9acbe9|Regimen=1}}==
 BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6ccf66|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,006: / Line 2,873: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3i|7+3i]], then [[#Amsacrine_.26_Cytarabine_.88|Amsacrine & Cytarabine]]
 {{#lst:Autologous HSCT|6ccf66}}
+</div></div>
 ===References===
 #'''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21951683 PubMed]
 ==BuFlu, then allo HSCT {{#subobject:3fe0f0|Regimen=1}}==
 BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a7e574|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,032: / Line 2,899: @@
 |}
 {{#lst:Allogeneic HSCT|a7e574}}
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div>
 ===References===
 <!-- Presented in part as an oral presentation at the 54th American Society of Hematology Annual Meeting and Exposition, Atlanta, GA, December 8-11, 2012. -->
 #'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780 PubMed] NCT00070135
 ==CIA {{#subobject:db5c09|Regimen=1}}==
 CIA: '''<u>C</u>'''lofarabine, '''<u>I</u>'''darubicin, '''<u>A</u>'''ra-C (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:1bbed8|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
@@ Line 3,056: / Line 2,922: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#CIA|CIA]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2
 *[[Cytarabine (Ara-C)]] 750 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''21- to 28-day cycle for up to 6 cycles; exact timing depends on disease response and recovery from regimen toxicity'''
+</div></div>
 ===References===
 #Nazha A, Kantarjian H, Ravandi F, Huang X, Choi S, Garcia-Manero G, Jabbour E, Borthakur G, Kadia T, Konopleva M, Cortes J, Ferrajoli A, Kornblau S, Daver N, Pemmaraju N, Andreeff M, Estrov Z, Du M, Brandt M, Faderl S. Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia. Am J Hematol. 2013 Nov;88(11):961-6. Epub 2013 Sep 9. [https://doi.org/10.1002/ajh.23544/references long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110914/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23877926 PubMed]
 ==CLARA {{#subobject:6160cf|Regimen=1}}==
 CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6ed739|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,090: / Line 2,953: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Cytarabine.2C_Daunorubicin.2C_G-CSF_88|Cytarabine, Daunorubicin, G-CSF]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 6, '''given first'''
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 4 hours after clofarabine, on days 2 to 5'''
 ====Growth factor therapy====
 *[[Filgrastim (Neupogen)]] 5 mcg/kg IV once per day on days 1 to 6
 '''35-day cycle for 3 cycles'''
+</div></div>
 ===References===
 #'''ALFA-0702:''' Thomas X, de Botton S, Chevret S, Caillot D, Raffoux E, Lemasle E, Marolleau JP, Berthon C, Pigneux A, Vey N, Reman O, Simon M, Recher C, Cahn JY, Hermine O, Castaigne S, Celli-Lebras K, Ifrah N, Preudhomme C, Terré C, Dombret H. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017 Apr 10;35(11):1223-1230. Epub 2017 Feb 21. [https://doi.org/10.1200/JCO.2016.70.4551 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28221862 PubMed] NCT00932412
 ==Clofarabine & LoDAC/Decitabine {{#subobject:756e06|Regimen=1}}==
 Clofarabine & LoDAC/Decitabine: Clofarabine & '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine) alternating with Decitabine
+<div class="toccolours" style="background-color:#eeeeee">
 ===Protocol {{#subobject:0ac883|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,123: / Line 2,981: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Clofarabine_.26_LoDAC|Clofarabine & LoDAC]], which is counted as "Cycle 1". Cycles are given every 4 to 7 weeks pending hematologic recovery and resolution of other toxicities.
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy, clofarabine & LoDAC portion====
 *[[Clofarabine (Clolar)]] as follows:
 **Cycles 2, 3, 7 to 9, 13 to 15: 20 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Cytarabine (Ara-C)]] as follows:
 **Cycles 2, 3, 7 to 9, 13 to 15: 20 mg SC twice per day on days 1 to 7
 '''4- to 7-week cycles, depending on count recovery'''
 ====Chemotherapy, decitabine portion====
 *[[Decitabine (Dacogen)]] as follows:
 **Cycles 4 to 6, 10 to 12, 16 to 18: 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 '''4- to 7-week cycles, depending on count recovery'''
+</div></div>
 ===References===
 #Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, Kadia T, Ferrajoli A, Konopleva M, Borthakur G, Burger J, Feliu J, Kantarjian HM. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012 Sep 15;118(18):4471-7. Epub 2012 Jan 26. [https://doi.org/10.1002/cncr.27429 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907176/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22282348 PubMed]
 ##'''Update:''' Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. Epub 2015 Mar 25. [https://doi.org/10.1002/cncr.29367 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436272/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25809968 PubMed]
 ==CPX-351 monotherapy {{#subobject:6a5fb5|Regimen=1}}==
 CPX-351: Liposomal Cytarabine and Daunorubicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:896083|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,162: / Line 3,014: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#CPX-351_monotherapy|CPX-351]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine and daunorubicin liposomal (Vyxeos)|CPX-351 (Vyxeos)]] 65 units/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 3
 '''5- to 8-week cycle for 2 cycles'''
+</div></div>
 ===References===
 <!-- # '''Abstract:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016 34:15_suppl, 7000-7000 [https://doi.org/10.1200/JCO.2016.34.15_suppl.7000 link to abstract] '''contains partial protocol''' [https://clinicaltrials.gov/ct2/show/NCT01696084 ClinicalTrials.gov] -->
 #'''CLTR0310-301:''' Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. Epub 2018 Jul 19. [https://doi.org/10.1200/JCO.2017.77.6112 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127025/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30024784 PubMed] NCT01696084
 ==Cytarabine & Daunorubicin {{#subobject:d6f810|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1 {{#subobject:c39b55|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,191: / Line 3,040: @@
 |}
 ''Note: the preceding treatment is not a true randomization because only patients in the gemtuzumab ozogamicin arm with platelet count less than 100 x 10<sup>9</sup> at day 45 from initiation of chemotherapy were assigned to this regimen.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3d_.28intermediate-dose.29|7+3d]]; intermediate-dose or [[#7.2B3d_.26_GO|7+3d & GO]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] as follows:
 **Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1
 **Cycle 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 '''2 cycles (length not specified)'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2 {{#subobject:59874e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,219: / Line 3,068: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B4d_88|4d + 7]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once on day 1
 '''1-month cycle for up to 6 cycles'''
+</div></div>
 ===References===
 #'''ALFA 9803:''' Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17341661 PubMed] NCT00363025
 #'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498
 ##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed]
 ==Cytarabine, Daunorubicin, Gemtuzumab ozogamicin {{#subobject:0f7f87|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c56261|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,249: / Line 3,095: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3d_.26_GO|7+3d & GO]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] as follows:
 **Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1
 **Cycle 2: 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV once on day 1
 '''2 cycles (length not specified)'''
+</div></div>
 ===References===
 #'''ALFA-0701:''' Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://doi.org/10.1016/S0140-6736(12)60485-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22482940 PubMed] NCT00927498
 ##'''Update:''' Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019 Jan;104(1):113-119. Epub 2018 Aug 3. [http://www.haematologica.org/content/104/1/113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30076173 PubMed]
 ==CYVE {{#subobject:f8d436|Regimen=1}}==
 CYVE: '''<u>CY</u>'''tarabine & '''<u>VE</u>'''pesid (Etoposide)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:79438d|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,286: / Line 3,127: @@
 |}
 ''Note: this consolidation regimen was for patients with high-risk cytogenetics.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose versus [[#7.2B3i|7+3i]]
-<div class="toccolours" style="width:100%; overflow:auto;">
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6
 *[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''4 courses'''
 </div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Transplant eligible patients with available donors usually proceeded to [[#Allogeneic_hematopoietic_stem_cell_transplant|allogeneic HSCT]] after 2 courses (details not specified)
+</div></div>
 ===References===
 #'''COSAH C-022:''' Lee JH, Kim H, Joo YD, Lee WS, Bae SH, Zang DY, Kwon J, Kim MK, Lee J, Lee GW, Lee JH, Choi Y, Kim DY, Hur EH, Lim SN, Lee SM, Ryoo HM, Kim HJ, Hyun MS, Lee KH; Cooperative Study Group A for Hematology. Prospective randomized comparison of idarubicin and high-dose daunorubicin in induction chemotherapy for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2017 Aug 20;35(24):2754-2763. Epub 2017 Jun 20. [https://doi.org/10.1200/JCO.2017.72.8618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632487 PubMed] NCT01145846
 ==Cytarabine & Idarubicin {{#subobject:f8c456|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:099908|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,322: / Line 3,161: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B4i_88|4i + 7]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 60 mg/m<sup>2</sup> SC every 12 hours on days 1 to 5 (total dose per cycle: 600 mg/m<sup>2</sup>)
 *[[Idarubicin (Idamycin)]] 9 mg/m<sup>2</sup> IV once on day 1
 '''1-month cycle for up to 6 cycles'''
+</div></div>
 ===References===
 #'''ALFA 9803:''' Gardin C, Turlure P, Fagot T, Thomas X, Terre C, Contentin N, Raffoux E, de Botton S, Pautas C, Reman O, Bourhis JH, Fenaux P, Castaigne S, Michallet M, Preudhomme C, de Revel T, Bordessoule D, Dombret H. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood. 2007 Jun 15;109(12):5129-35. Epub 2007 Mar 6. [http://www.bloodjournal.org/content/109/12/5129.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17341661 PubMed] NCT00363025
 ==Cytarabine, Idarubicin, Sorafenib {{#subobject:8c0061|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:97a478|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,351: / Line 3,187: @@
 |}
 ''Regimen details are from the phase 2 part of the published phase 1/2 trial.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3i_.26_Sorafenib|7+3i & Sorafenib]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 2250 mg/m<sup>2</sup>)
 *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2
 ====Targeted therapy====
 *[[Sorafenib (Nexavar)]] 400 mg PO twice per day for up to 28 days
 '''4- to 6-week cycle for up to 5 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#Sorafenib_monotherapy|Sorafenib]] maintenance
+</div></div>
 ===References===
 <!-- no pre-pub disclosed -->
 #'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971
 ##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed]
 ==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}==
 Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:6ca28d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,409: / Line 3,241: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Zittoun et al. 1995: [[#7.2B3d_.28standard-dose.29|7+3d]] with CR, then [[Stub#Amsacrine_.26_IDAC|Amsacrine & IDAC]]
 {{#lst:Allogeneic HSCT|6ca28d}}
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div>
 ===References===
 #Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. [https://doi.org/10.1056/NEJM198005083021901 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6245359 PubMed]
 #Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; [[Study_Groups#EORTC|EORTC]]; GIMEMA. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. [https://doi.org/10.1056/NEJM199501263320403 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7808487 PubMed]
 #'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22959335 PubMed] NCT00150878
 #'''Retrospective:''' Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. [http://www.bloodjournal.org/content/122/24/3863.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854108/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24065243 PubMed]
 ==Etoposide & Mitoxantrone {{#subobject:ab1766|Regimen=1}}==
 ME: '''<u>M</u>'''itoxantrone & '''<u>E</u>'''toposide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 3 days {{#subobject:78ghc3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,444: / Line 3,275: @@
 |}
 ''Note: this dosing was intended for patients older than 60. Dosing information is from CT.gov.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3d_.28intermediate-dose.29|7+3d]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
 '''One course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 5 days {{#subobject:780933|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,469: / Line 3,301: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3i|7+3i]], then [[#Amsacrine_.26_Cytarabine_88|Amsacrine & Cytarabine]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 5
 '''One course'''
+</div></div>
 ===References===
 #'''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; HOVON; SAKK. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [http://www.bloodjournal.org/content/118/23/6037.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21951683 PubMed]
 #'''AMLSG31-19:''' NCT04628026
 ==Fludarabine & TBI, then allo HSCT {{#subobject:53c6af|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1 {{#subobject:be3609|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,505: / Line 3,335: @@
 {{#lst:Allogeneic HSCT|be3609}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, low-dose TBI{{#subobject:7fa6ce|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,522: / Line 3,352: @@
 {{#lst:Allogeneic HSCT|7fa6ce}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div>
 ===References===
 <!-- no pre-pub disclosed -->
 #Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626 PubMed]
 #'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22959335 PubMed] NCT00150878
 ==Fludarabine, Busulfan, ATG, then allo HSCT {{#subobject:ed545b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:dd1486|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,547: / Line 3,374: @@
 {{#lst:Allogeneic HSCT|dd1486}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div>
 ===References===
 <!-- Presented in part as an oral presentation at the 54th American Society of Hematology Annual Meeting and Exposition, Atlanta, GA, December 8-11, 2012. -->
 #'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780 PubMed] NCT00070135
 ==HAM {{#subobject:1da5a5|Regimen=1}}==
 HAM: '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''itoxantrone
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:eb86c6|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,575: / Line 3,398: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *Wierzbowska et al. 2007: [[#CLAG-M|CLAG-M]]
 *PALG AML1/2004: [[#7.2B3d_.28intermediate-dose.29|DA]] versus [[#DAC|DAC]] versus [[#DAF_99|DAF]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 3
 *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 3 to 5
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29|HiDAC]] consolidation
+</div></div>
 ===References===
 #Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. [https://doi.org/10.1111/j.1600-0609.2007.00988.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18076637 PubMed] content property of [http://hemonc.org HemOnc.org]
 #'''PALG AML1/2004:''' Holowiecki J, Grosicki S, Giebel S, Robak T, Kyrcz-Krzemien S, Kuliczkowski K, Skotnicki AB, Hellmann A, Sulek K, Dmoszyńska A, Kloczko J, Jedrzejczak WW, Zdziarska B, Warzocha K, Zawilska K, Komarnicki M, Kielbinski M, Piatkowska-Jakubas B, Wierzbowska A, Wach M, Haus O. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012 Jul 10;30(20):2441-8. Epub 2012 Apr 16. [https://doi.org/10.1200/jco.2011.37.1286 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22508825 PubMed]
 ==IC & Norethandrolone/6-MP, MTX, Norethandrolone {{#subobject:2034a1|Regimen=1}}==
 IC & Norethandrolone: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, Norethandrolone
+<div class="toccolours" style="background-color:#eeeeee">
 ===Protocol {{#subobject:0849b9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,611: / Line 3,432: @@
 | style="background-color:#1a9850" |Superior OS
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#ICL|7+3i & Lomustine]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy, reinduction====
 *[[Idarubicin (Idamycin)]] 8 mg/m<sup>2</sup> IV once on day 1
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m<sup>2</sup>)
 ====Endocrince therapy, reinduction====
 *[[Norethandrolone (Nilevar)]] by the following weight-based criteria:
 **If less than 60 kg: 10 mg PO once per day
 **If greater than 60 kg: 20 mg PO once per day
 '''3-month cycle for 6 cycles, alternating with maintenance'''
 ====Chemotherapy, maintenance====
 *[[Methotrexate (MTX)]] by the following weight-based criteria:
 **If less than 60 kg: 20 mg PO once per day on days 1, 4, 8, 11
@@ Line 3,635: / Line 3,452: @@
 **If less than 60 kg: 100 mg PO once per day on days 15 to 30
 **If greater than 60 kg: 150 mg PO once per day on days 15 to 30
 ====Endocrine therapy, maintenance====
 *[[Norethandrolone (Nilevar)]] by the following weight-based criteria:
 **If less than 60 kg: 10 mg PO once per day
 **If greater than 60 kg: 20 mg PO once per day
 '''3-month cycle for 6 cycles, alternating with re-induction courses'''
+</div></div>
 ===References===
 #'''GOELAMS LAM-SA2002:''' Pigneux A, Béné MC, Guardiola P, Recher C, Hamel JF, Sauvezie M, Harousseau JL, Tournilhac O, Witz F, Berthou C, Escoffre-Barbe M, Guyotat D, Fegueux N, Himberlin C, Hunault M, Delain M, Lioure B, Jourdan E, Bauduer F, Dreyfus F, Cahn JY, Sotto JJ, Ifrah N. Addition of androgens improves survival in elderly patients with acute myeloid leukemia: a GOELAMS study. J Clin Oncol. 2017 Feb;35(4):387-393. Epub 2016 Oct 24. [https://doi.org/10.1200/JCO.2016.67.6213 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28129526 PubMed] NCT00700544
 ==Low-dose TBI, then allo HSCT {{#subobject:529ee7|Regimen=1}}==
 TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:174a8e|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,664: / Line 3,476: @@
 {{#lst:Allogeneic HSCT|174a8e}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div>
 ===References===
 <!-- no pre-pub disclosed -->
 #Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626 PubMed]
 =Maintenance after first-line therapy=
 ''Note: with a few exceptions, these regimens are given as part of a non-curative line of therapy.''
 ==Azacitidine monotherapy {{#subobject:887fd6|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 12 cycles {{#subobject:482f12|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,692: / Line 3,501: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *At least 2 cycles of [[Regimen_classes#Intensive_chemotherapy|intensive chemotherapy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Azacitidine (Vidaza)]] 50 mg/m<sup>2</sup> SC once per day on days 1 to 5
 '''28-day cycle for up to 12 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, indefinite {{#subobject:482f11|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,714: / Line 3,523: @@
 |}
 ''Intended to be used for transformed MDS patients in remission after AML induction therapy.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B2d_88|7+2d]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Azacitidine (Vidaza)]] 60 mg/m<sup>2</sup> SC once per day on days 1 to 5
 '''28-day cycles'''
+</div></div>
 ===References===
 #Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. [https://doi.org/10.1111/j.1365-2141.2010.08235.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20497178 PubMed]
 #'''HOVON97:''' Huls G, Chitu DA, Havelange V, Jongen-Lavrencic M, van de Loosdrecht AA, Biemond BJ, Sinnige H, Hodossy B, Graux C, Kooy RVM, de Weerdt O, Breems D, Klein S, Kuball J, Deeren D, Terpstra W, Vekemans MC, Ossenkoppele GJ, Vellenga E, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group. Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. Blood. 2019 Mar 28;133(13):1457-1464. Epub 2019 Jan 10. [https://doi.org/10.1182/blood-2018-10-879866 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30630862 PubMed] NTR1810
 ==Decitabine monotherapy {{#subobject:d8250a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:4726aa|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,744: / Line 3,549: @@
 |}
 ''Blum et al. 2010 did not clearly state whether decitabine maintenance is at the same dosage/frequency as induction therapy. This is the inferred dosage from the paper.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Decitabine_monotherapy|Decitabine]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 **Patients with no evidence of residual disease by flow cytometry or cytogenetics who had grade 4 neutropenia (ANC less than 500/uL) persisting greater than or equal to 14 days received 4 days instead of 5 days of decitabine starting with the following cycle. If neutropenia occurred again as above with 4 days of decitabine, patients received 3 days instead of 4 days of decitabine starting with the following cycle.
 '''28-day cycles'''
+</div></div>
 ===References===
 #'''OSU 07017:''' Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. Epub 2010 Apr 5. [http://www.pnas.org/content/107/16/7473.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20368434 PubMed] NCT00492401
 ==Azacitidine oral monotherapy {{#subobject:da9efa|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:90f116|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,777: / Line 3,579: @@
 |}
 ''<sup>1</sup>The proportional hazards assumption was violated, so hazard ratios are not reported.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Regimen_classes#Chemotherapy|Induction chemotherapy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Azacitidine oral (Onureg)]] 300 mg PO once per day on days 1 to 14
 '''28-day cycle'''
+</div></div>
 ===References===
 #'''QUAZAR AML-001:''' Wei AH, Döhner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, Ravandi F, Sayar H, Jang JH, Porkka K, Selleslag D, Sandhu I, Turgut M, Giai V, Ofran Y, Kizil Çakar M, Botelho de Sousa A, Rybka J, Frairia C, Borin L, Beltrami G, Čermák J, Ossenkoppele GJ, La Torre I, Skikne B, Kumar K, Dong Q, Beach CL, Roboz GJ; QUAZAR AML-001 Trial Investigators. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med. 2020 Dec 24;383(26):2526-2537. [https://doi.org/10.1056/nejmoa2004444 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33369355 PubMed] NCT01757535
 ==Gemtuzumab ozogamicin monotherapy {{#subobject:39de3d|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:b7c813|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
@@ Line 3,804: / Line 3,603: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Gemtuzumab_ozogamicin_monotherapy|Gemtuzumab ozogamicin]] induction, with clinical benefit
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 2 mg/m<sup>2</sup> IV once on day 1
 '''1-month cycle for up to 8 cycles'''
+</div></div>
 ===References===
 <!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
 #'''EORTC/GIMEMA AML-19:''' Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F; EORTC; GIMEMA. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [https://doi.org/10.1200/jco.2015.64.0060 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26811524 PubMed] NCT00091234
 ==Low-dose Cytarabine monotherapy (LoDAC) {{#subobject:4c65c8|Regimen=1}}==
 LoDAC: '''<u>Lo</u>'''w '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
 <br>LDAC: '''<u>L</u>'''ow '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:2f5aa0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,839: / Line 3,634: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#High-dose_Cytarabine_monotherapy_.28HiDAC.29_88|HiDAC]], then [[#Amsacrine_monotherapy_88|amsacrine]] induction
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 10 mg/m<sup>2</sup> SC twice per day on days 1 to 21
 '''8-week cycles'''
+</div></div>
 ===References===
 #'''ECOG E5483:''' Robles C, Kim KM, Oken MM, Bennett JM, Letendre L, Wiernik PH, O'Connell MJ, Cassileth PA. Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483). Leukemia. 2000 Aug;14(8):1349-53. [https://www.nature.com/articles/2401850 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10942228 PubMed]
 ==Sorafenib monotherapy {{#subobject:23822e|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:b50325|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,867: / Line 3,658: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#Cytarabine.2C_Idarubicin.2C_Sorafenib|Cytarabine, Idarubicin, Sorafenib]] consolidation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Sorafenib (Nexavar)]] 400 mg PO twice per day
 '''Up to one year course, including consolidation'''
+</div></div>
 ===References===
 <!-- no pre-pub disclosed -->
 #'''BAY43-9006:''' Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.4888 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20212254 PubMed] NCT00542971
 ##'''Update:''' Ravandi F, Arana Yi C, Cortes JE, Levis M, Faderl S, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce S, Brandt M, Pratz K, Luthra R, Andreeff M, Kantarjian H. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia. 2014 Jul;28(7):1543-5. Epub 2014 Feb 3. [https://doi.org/10.1038/leu.2014.54 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091714/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24487412 PubMed]
 =Relapsed or refractory, salvage therapy=
 ''Note: these are generally aggressive regimens intended to induce a second remission as part of a path towards pre-planned allogeneic HSCT.''
 ==5+2d {{#subobject:df9bab|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c9d569|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,898: / Line 3,686: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[#7.2B3d_.28high-dose.29|7+3d]]; high-dose
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 500 mg/m<sup>2</sup>)
 *[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 & 2
 '''5-day course'''
+</div></div>
 ===References===
 #'''JHOC-J1101:''' Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. Epub 2015 May 28. [http://www.haematologica.org/content/100/9/1172 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26022709 PubMed] NCT01349972
 ==ADE (standard-dose Ara-C) {{#subobject:d16134|Regimen=1}}==
 ADE: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a99e51|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 3,932: / Line 3,716: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] as follows:
 **Course 1: 100 mg/m<sup>2</sup> IV push every 12 hours on days 1 to 10 (total dose: 2000 mg/m<sup>2</sup>)
@@ Line 3,940: / Line 3,723: @@
 *[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 '''2 courses (length not specified)'''
+</div></div>
 ===References===
 #'''MRC AML-HR:''' Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK; NCRI Haematological Oncology Clinical Studies Group. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood. 2006 Jun 15;107(12):4614-22. Epub 2006 Feb 16. [http://www.bloodjournal.org/content/107/12/4614.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16484584 PubMed] NCT00005863
 ==CLAG {{#subobject:702383|Regimen=1}}==
 CLAG: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:12d1bb|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,962: / Line 3,741: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first'''
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 2 hours after cladribine'''
 ====Growth factor therapy====
 *[[Filgrastim (Neupogen)]] 300 mcg SC once per day on days -1 to 5 (first dose is given 24 hours before first dose of cladribine)
+</div></div>
 ===References===
 #Robak T, Wrzesień-Kuś A, Lech-Marańda E, Kowal M, Dmoszyńska A. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2000 Sep;39(1-2):121-9. [https://doi.org/10.3109/10428190009053545 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10975390 PubMed]
 #'''Retrospective:''' Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. [https://pubmed.ncbi.nlm.nih.gov/19717379 PubMed]
 ==CLAG-M {{#subobject:51b417|Regimen=1}}==
 CLAG-M: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF, '''<u>M</u>'''itoxantrone
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:e0b308|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 3,990: / Line 3,765: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first'''
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 2 hours after cladribine'''
 *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
 ====Growth factor therapy====
 *[[Filgrastim (Neupogen)]] by the following criteria:
 **WBC count less than or equal to 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 0 to 5, '''started 24 hours prior to chemotherapy'''
 **WBC count greater than 20 x 10<sup>9</sup>/L: 300 mcg SC once per day on days 1 to 5, '''started simultaneously to cladribine'''
 '''6-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients with PR were recommended to undergo a second course of [[#CLAG-M|CLAG-M]].
 **Primary refractory patients achieving CR after 2nd CLAG-M: [[#HAM|HAM]] consolidation
 *Others could receive another course of CLAG-M or [[#HAM|HAM]] consolidation per investigator discretion
+</div></div>
 ===References===
 #Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Holowiecki J, Kyrcz-Krzemien S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kielbinski M, Zawilska K, Kloczko J, Wrzesień-Kuś A; Polish Adult Leukemia Group. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008 Feb;80(2):115-26. Epub 2007 Dec 11. [https://doi.org/10.1111/j.1600-0609.2007.00988.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18076637 PubMed] content property of [http://hemonc.org HemOnc.org]
 #'''Retrospective:''' Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN. Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma. 2009 Aug;9(4):298-301. [https://pubmed.ncbi.nlm.nih.gov/19717379 PubMed]
 ==CLARA {{#subobject:48978a|Regimen=1}}==
 CLARA: '''<u>CL</u>'''ofarabine and '''<u>ARA</u>'''-C (Cytarabine)
 <br>GCLAC: '''<u>G</u>'''-CSF, '''<u>C</u>'''lofarabine, '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:b8a3a2|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,029: / Line 3,800: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 25 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first'''
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after start of clofarabine infusion'''
 ====Growth factor therapy====
 *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting day -1, continuing until ANC at least 2000/uL for 2 consecutive days
 '''6-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Patients with greater than 5% blasts at day 21: [[#CLARA_2|CLARA]] re-induction x 1
 *Patients achieving CR: Optional [[#CLARA_3|CLARA]] consolidation for up to 2 cycles
+</div></div>
 ===References===
 #'''UW 6562:''' Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol. 2011 Oct;155(2):182-9. Epub 2011 Aug 18. [https://doi.org/10.1111/j.1365-2141.2011.08831.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834701/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21848522 PubMed] NCT00602225
 ==Clofarabine & Cytarabine {{#subobject:23e3f2|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 20/20 variant 1 {{#subobject:d4a73c|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,061: / Line 3,828: @@
 |-
 |}
-''The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.''
+''Note: The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5
 *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC twice per day on days 1 to 10
 '''Cycle duration not explicitly defined; presumably 28 days'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 20/20 variant 2 {{#subobject:dhg73c|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,080: / Line 3,847: @@
 |-
 |}
-''The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.''
+''Note: The dose of clofarabine is the one reported as the MTD. Note that the doses of both drugs are much lower than the other variants here.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 20 mg PO once per day on days 1 to 5
 *[[Cytarabine (Ara-C)]] 20 mg/m<sup>2</sup> SC once per day on days 1 to 14
 '''Cycle duration not explicitly defined; presumably 28 days'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 30/1000 {{#subobject:f6ada8|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,099: / Line 3,866: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 5
 '''At least one cycle'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *Chemo-responsive patients: [[#Clofarabine_.26_Melphalan.2C_then_allo_HSCT|Clofarabine & Melphalan, then allo HSCT]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #4, 40/1000 {{#subobject:d95457|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,137: / Line 3,905: @@
 |}
 ''Note: length of cycles was not specified; 28-day cycle is typical for this regimen.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Clofarabine (Clolar)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given first'''
 **Note: in Faderl et al. 2004, clofarabine was given on days 2 to 6
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given second, 3 to 4 hours after completion of clofarabine infusion'''
 ====Supportive therapy====
 *Best described in Agura et al. 2011
 *[[Dexamethasone (Decadron)]] 10 mg IV once per day
@@ Line 4,157: / Line 3,923: @@
 *Parenteral nutrition allowed
 *No routine use of growth factors
 '''28-day cycle for 1 to 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *See individual papers for details
+</div></div>
 ===References===
 #Faderl S, Gandhi V, O'Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H. Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005 Feb 1;105(3):940-7. Epub 2004 Oct 14. [http://www.bloodjournal.org/content/105/3/940.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15486072 PubMed]
 #'''Baylor 004-145:''' Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist. 2011;16(2):197-206. Epub 2011 Jan 27. [http://theoncologist.alphamedpress.org/content/16/2/197.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228084/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21273514 PubMed] NCT00334074
@@ Line 4,171: / Line 3,936: @@
 #'''FHCRC 2302.00:''' Buckley SA, Mawad R, Gooley TA, Becker PS, Sandhu V, Hendrie P, Scott BL, Wood BL, Walter RB, Smith K, Dean C, Estey EH, Pagel JM. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age. Br J Haematol. 2015 Aug;170(3):349-55. Epub 2015 Apr 8. [https://doi.org/10.1111/bjh.13437 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25854284 PubMed]
 #'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26283567 PubMed]
 ==Etoposide & Mitoxantrone {{#subobject:3f0d63|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:7683cc|Variant=1}}===
 {| class="wikitable sortable" style="width: 80%; text-align:center;"
@@ Line 4,187: / Line 3,951: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
 *[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 to 5
+</div></div>
 ===References===
 #Ho AD, Lipp T, Ehninger G, Illiger HJ, Meyer P, Freund M, Hunstein W. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen. J Clin Oncol. 1988 Feb;6(2):213-7. [https://doi.org/10.1200/jco.1988.6.2.213 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3422260 PubMed]
 ==FLAG {{#subobject:551761|Regimen=1}}==
 FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:9501d2|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,210: / Line 3,972: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first'''
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after the start of fludarabine'''
 ====Growth factor therapy====
 *G-CSF with one of the following:
 **[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery
 **[[Lenograstim (Granocyte)]] 5 mcg/kg SC once per day, starting on day -1 (the paper described this as day 0), first dose given 24 hours before first dose of chemotherapy, to continue until neutrophil recovery
 '''6-day course'''
+</div></div>
 ===References===
 #Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F. Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol. 1998 Jun;58(2):105-9. [https://doi.org/10.1002/(sici)1096-8652(199806)58:2%3C105::aid-ajh3%3E3.0.co;2-w link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9625576 PubMed]
 ==FLAG-Ida {{#subobject:d8c75b|Regimen=1}}==
 FLAG-Ida: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>G</u>'''-CSF (Filgrastim), '''<u>Ida</u>'''rubicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:5fa1bb|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,246: / Line 4,003: @@
 |}
 ''Note: although this regimen is described as FLAG-Ida, the G-CSF starts on day 6 and is therefore considered as a supportive medication, not an antineoplastic.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first'''
 *[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5, '''given second, 4 hours after fludarabine'''
 *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
 ====Supportive therapy====
 *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6, to continue until neutrophil recovery
 '''5-day course'''
+</div></div>
 ===References===
 #Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM, Samaratunga IR, Grace R, Gover PA, Mufti GJ. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997 Dec;99(4):939-44. [https://doi.org/10.1046/j.1365-2141.1997.4763281.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/9432047 PubMed]
 #Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. Epub 2003 Mar 15. [https://doi.org/10.1007/s00277-003-0624-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12707726 PubMed]
 ==F-SHAI {{#subobject:9e1c5f|Regimen=1}}==
 F-SHAI: '''<u>F</u>'''ludarabine, '''<u>S</u>'''equential '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), '''<u>I</u>'''darubicin
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:b50224|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,282: / Line 4,034: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Fludarabine (Fludara)]] 15 mg/m<sup>2</sup> IV twice per day on days 1, 2, 8, 9, '''given 4 hours prior to each cytarabine dose'''
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV twice per day on days 1, 2, 8, 9
 **Dose increased to 3000 mg/m<sup>2</sup> for patients 60 or younger with refractory AML or greater than or equal to 2nd relapse
 *[[Idarubicin (Idamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 3, 4, 10, 11
 ====Supportive therapy====
 *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] 5 mcg/kg SC once per day, starting on day 14 and continuing until ANC greater than 1500/uL
 **Discontinued if the post-treatment bmbx had greater than 5% bone marrow blasts
 '''11-day course'''
+</div></div>
 ===References===
 #Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W. Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. Epub 2013 Oct 22. [https://doi.org/10.1038/leu.2013.297 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24150216 PubMed]
 ==Gemtuzumab ozogamicin monotherapy {{#subobject:4e1hba|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, fractionated dosing {{#subobject:jgaci5|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,313: / Line 4,060: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m<sup>2</sup> IV once per day on days 1, 4, 7
 '''One course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2 {{#subobject:e0aci5|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,331: / Line 4,078: @@
 |}
 ''Note: this is one of the trials that led to FDA accelerated approval in 2000; a subsequent confirmatory trial was negative. Due to the high toxicities at this dosing level, this variant should be considered of historical interest, only.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Antibody-drug conjugate therapy====
 *[[Gemtuzumab ozogamicin (Mylotarg)]] 9 mg/m<sup>2</sup> IV once on day 1
 '''14-day cycle for 2 cycles'''
+</div></div>
 ===References===
 # Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. [https://doi.org/10.1200/jco.2001.19.13.3244 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11432892 PubMed]
@@ Line 4,342: / Line 4,088: @@
 ## '''Update:''' Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, Theobald M, Voliotis D, Bennett JM, Richie M, Leopold LH, Berger MS, Sherman ML, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005 Oct 1;104(7):1442-52. [https://doi.org/full/10.1002/cncr.21326 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16116598 PubMed]
 #'''MyloFrance-1:''' Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, Bouabdallah R, Pautas C, Turlure P, Reman O, Gardin C, Varet B, de Botton S, Pousset F, Farhat H, Chevret S, Dombret H, Castaigne S. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. 2007 Jan;21(1):66-71. Epub 2006 Oct 19. [https://doi.org/10.1038/sj.leu.2404434 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17051246/ PubMed]
 ==High-dose Cytarabine monotherapy (HiDAC) {{#subobject:1dddf5|Regimen=1}}==
 HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, CI {{#subobject:e8a7af|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,362: / Line 4,107: @@
 |}
 ''Note: while the experimental arm of this trial met the primary endpoint of ORR, the control arm had superior PFS.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 7500 mg/m<sup>2</sup>)
 '''3-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, intermittent {{#subobject:ab6f08|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,383: / Line 4,128: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 6 (total dose: 36,000 mg/m<sup>2</sup>)
 '''6-day course'''
+</div></div>
 ===References===
 #'''SWOG-8326:''' Karanes C, Kopecky KJ, Head DR, Grever MR, Hynes HE, Kraut EH, Vial RH, Lichtin A, Nand S, Samlowski WE, Appelbaum FR. A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res. 1999 Sep;23(9):787-94. [https://doi.org/10.1016/s0145-2126(99)00087-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10475617 PubMed]
 #'''VION-CLI-037:''' Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S. Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse. Blood. 2009 Nov 5;114(19):4027-33. Epub 2009 Aug 26. [http://www.bloodjournal.org/content/114/19/4027.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19710500 PubMed] NCT00112554
 ==MAC {{#subobject:fba448|Regimen=1}}==
 MAC: '''<u>M</u>'''itoxantrone & '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 <br>MIDAC: '''<u>M</u>'''itoxantrone & '''<u>I</u>'''ntermediate-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 6000/25 {{#subobject:5bf868|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,408: / Line 4,151: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mitoxantrone (Novantrone)]] 5 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 *[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV over 90 minutes every 12 hours on days 1 to 6 (total dose: 6000 mg/m<sup>2</sup>)
 '''6-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 10,000/48 {{#subobject:4a2f44|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,430: / Line 4,173: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV bolus once per day on days 2 to 5
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 5 (total dose: 10,000 mg/m<sup>2</sup>)
 '''5-day course'''
+</div></div>
 ===References===
 #Solary E, Witz B, Caillot D, Moreau P, Desablens B, Cahn JY, Sadoun A, Pignon B, Berthou C, Maloisel F, Guyotat D, Casassus P, Ifrah N, Lamy Y, Audhuy B, Colombat P, Harousseau JL. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood. 1996 Aug 15;88(4):1198-205. [http://www.bloodjournal.org/content/88/4/1198.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8695837 PubMed]
 #Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer. 2000 May 1;88(9):2037-41. [https://doi.org/10.1002/(sici)1097-0142(20000501)88:9%3C2037::aid-cncr8%3E3.0.co;2-k link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10813714 PubMed]
 ==MEC {{#subobject:48e49b|Regimen=1}}==
 MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 6/80/1000 {{#subobject:ac3985|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,456: / Line 4,196: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV bolus once per day on days 1 to 6
 *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 6
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 6
 '''6-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 8/80/1000 {{#subobject:9ad362|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,479: / Line 4,219: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 to 6
 *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 6
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 6
 '''6-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 8/100/1000 {{#subobject:bd7f87|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,509: / Line 4,249: @@
 |}
 ''Note: this was the most commonly used salvage regimen in the control arm of CLTR0308-205; exact dosing details were not described in the paper.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV push once per day on days 1 to 5, '''given third'''
 *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, '''given first'''
 *[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given second'''
 '''28-day cycle for 1 to 2 cycles'''
+</div></div>
 ===References===
 #Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F. Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol. 1991 Jul;9(7):1210-4. [https://doi.org/10.1200/jco.1991.9.7.1210 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2045861 PubMed]
 #'''ECOG E2995:''' Greenberg PL, Lee SJ, Advani R, Tallman MS, Sikic BI, Letendre L, Dugan K, Lum B, Chin DL, Dewald G, Paietta E, Bennett JM, Rowe JM. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol. 2004 Mar 15;22(6):1078-86. Erratum in: J Clin Oncol. 2004  Jul 1;22(13):2747. [https://doi.org/10.1200/JCO.2004.07.048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457168/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020609 PubMed]
@@ Line 4,523: / Line 4,262: @@
 #'''CLTR0308-205:''' Cortes JE, Goldberg SL, Feldman EJ, Rizzeri DA, Hogge DE, Larson M, Pigneux A, Recher C, Schiller G, Warzocha K, Kantarjian H, Louie AC, Kolitz JE. Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer. 2015 Jan 15;121(2):234-42. Epub 2014 Sep 15. [https://doi.org/10.1002/cncr.28974 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542857/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25223583 PubMed] NCT00822094
 #'''D18-11141:''' NCT03926624
 =Consolidation after salvage therapy=
 ==BuCy, then allo HSCT {{#subobject:83e07a|Regimen=1}}==
 BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 12.8/120 {{#subobject:eeaff3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,551: / Line 4,289: @@
 {{#lst:Allogeneic HSCT|eeaff3}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 16/200 {{#subobject:334af6|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,568: / Line 4,306: @@
 {{#lst:Allogeneic HSCT|334af6}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div>
 ===References===
 #Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. [https://doi.org/10.1056/NEJM198312013092202 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/6355849 PubMed]
 #'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297 PubMed] NCT01191957
 #'''BMT CTN 0901:''' Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. Epub 2017 Feb 13. [https://doi.org/10.1200/JCO.2016.70.7091 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455603/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28380315 PubMed] NCT01339910
 ==BuFlu, then allo HSCT {{#subobject:576283|Regimen=1}}==
 BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine
 <br>Flu/Bu: '''<u>Flu</u>'''darabine & '''<u>Bu</u>'''sulfan
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1 {{#subobject:d415a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,599: / Line 4,334: @@
 {{#lst:Allogeneic HSCT|d415a}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2 {{#subobject:d415b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,619: / Line 4,354: @@
 {{#lst:Allogeneic HSCT|d415b}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3 {{#subobject:d415c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,641: / Line 4,375: @@
 {{#lst:Allogeneic HSCT|d415c}}
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div>
 ===References===
 #Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. [http://www.bbmt.org/article/S1083-8791(08)00118-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18489993 Pubmed]
 #'''COSAH C-005:''' Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. [https://doi.org/10.1200/jco.2011.40.2362 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23129746 PubMed] NCT00774280
 #'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297 PubMed] NCT01191957
 ==Clofarabine & Melphalan, then allo HSCT {{#subobject:08947a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a408ed|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,663: / Line 4,394: @@
 | style="background-color:#91cf61" |Phase 2
 |-
 |}
 ''Limited details are available in the abstract. Treatment is meant to be given during aplasia.''
-====Preceding treatment====
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
 *[[#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine]] salvage
 {{#lst:Allogeneic HSCT|a408ed}}
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Immunotherapy====
 *[[Allogeneic stem cells]]
 '''Stem cells transfused on day 0'''
+</div></div>
 ===References===
 #'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26283567 PubMed]
 =Relapsed or refractory, subsequent lines of therapy=
 ''Note: these regimens are generally intended to delay progression of disease and are of non-curative intent.''
 ==Azacitidine monotherapy {{#subobject:531b70|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:39f96a|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 4,705: / Line 4,434: @@
 |}
 ''Note: CLAVELA does not contain precise dosing information for the control arm regimens.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Azacitidine (Vidaza)]] 75 mg/m<sup>2</sup> SC once per day on days 1 to 7
 '''28-day cycle for at least 4 cycles'''
+</div></div>
 ===References===
 <!-- no pre-pub disclosed -->
 #Thepot S, Itzykson R, Seegers V, Raffoux E, Quesnel B, Chait Y, Sorin L, Dreyfus F, Cluzeau T, Delaunay J, Sanhes L, Eclache V, Dartigeas C, Turlure P, Harel S, Salanoubat C, Kiladjian JJ, Fenaux P, Adès L; Groupe Francophone des Myelodysplasies. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010 Nov 11;116(19):3735-42. Epub 2010 Jul 27. [http://www.bloodjournal.org/content/116/19/3735.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20664061 PubMed]
 #'''CLAVELA:''' Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss Ø, Vetrhusand S, Giles FJ. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol. 2014 Jun 20;32(18):1919-26. Epub 2014 May 19. [https://doi.org/10.1200/jco.2013.52.8562 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/24841975/ PubMed] NCT01147939
 ==Ruxolitinib monotherapy {{#subobject:ad5c7c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:596d8b|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 4,731: / Line 4,456: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Ruxolitinib (Jakafi)]] 25 mg PO twice per day
 **Patients with progression were allowed to increase the dose to 50 mg PO twice per day
 '''28-day cycles'''
+</div></div>
 ===References===
 <!-- This study was presented in part at the American Society of Hematology annual meeting, December 2010, Orlando, FL. -->
 #'''MDACC 2007-0925:''' Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C, Faderl S, Ferrajoli A, Borthakur G, George S, Scherle PA, Newton RC, Kantarjian HM, Ravandi F. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood. 2012 May 17;119(20):4614-8. Epub 2012 Mar 15. [http://www.bloodjournal.org/content/119/20/4614.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081383/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22422826 PubMed]
 =Response criteria=
 ==NCI-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia (1990)==
 #Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD, Brunning R, Gale RP, Grever MR, Keating MJ, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990 May;8(5):813-9. [https://doi.org/10.1200/jco.1990.8.5.813 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2185339 PubMed]
 ==Revised International Working Group recommendations (2003)==
 #Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. Erratum in: J Clin Oncol. 2004 Feb 1;22(3):576. LoCocco, Francesco [corrected to Lo-Coco, Francesco]. [https://doi.org/10.1200/jco.2003.04.036 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14673054 PubMed]
 =Prognosis=
 ==Prognostic Index for Adult Patients With Acute Myeloid Leukemia in First Relapse (2005)==
 *Relapse-free interval from first complete remission
 **Greater than 18 months (0 points)
@@ Line 4,772: / Line 4,487: @@
 **No (0 points)
 **Yes, autologous or allogeneic ('''2 points''')
 Risk stratification:
 *'''1 to 6 points''': Favorable risk (1-year OS of 70%; 5-year OS of 46%)
 *'''7 to 9 points''': Intermediate risk (1-year OS of 49%; 5-year OS of 18%)
 *'''10 to 14 points''': Poor risk (1-year OS of 16%; 5-year OS of 4%)
+</div></div>
 ===References===
 #Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, Vellenga E, De Greef GE, Jacky E, Van der Lelie J, Boogaerts MA, Löwenberg B. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005 Mar 20;23(9):1969-78. Epub 2005 Jan 4. [https://doi.org/10.1200/jco.2005.06.027 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15632409 PubMed]
 ==Prognosis in cytogenetically normal AML==
 #''Seminal paper comparing the mutational status of NPM1, FLT3, CEBPA, MLL, and NRAS with clinical outcome:'' Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008 May 1;358(18):1909-18. [https://doi.org/10.1056/NEJMoa074306 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18450602 PubMed]
 #''CEBPA double mutations:'' Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009 Mar 26;113(13):3088-91. Epub 2009 Jan 26. [https://ashpublications.org/blood/article/113/13/3088/24746/Double-CEBPA-mutations-but-not-single-CEBPA link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19171880 PubMed]
 ==Whole genome sequencing==
 #''Seminal paper comparing WGS to cytogenetic analysis:'' Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S, Bohannon A, Kruchowski S, Garza J, Du F, Hughes AEO, Robinson J, Hughes E, Heath SE, Baty JD, Neidich J, Christopher MJ, Jacoby MA, Uy GL, Fulton RS, Miller CA, Payton JE, Link DC, Walter MJ, Westervelt P, DiPersio JF, Ley TJ, Spencer DH. Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers. N Engl J Med. 2021 Mar 11;384(10):924-935. [https://doi.org/10.1056/nejmoa2024534 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33704937/ PubMed]
 =Investigational agents=
 ''These are drugs under study with at least some promising results for this disease.''
 *[[Alvocidib (Flavopiridol)]]
 *[[Pracinostat (SB939)]]
@@ Line 4,800: / Line 4,506: @@
 *[[Volasertib (BI 6727)]]
 *[[Vosaroxin (SNS 595)]]
 =Additional information=
 [[Category:Acute myeloid leukemia regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Acute leukemias]]

Difference between revisions of "Acute myeloid leukemia"

Revision as of 12:09, 16 October 2022

Guidelines

ASH

ELN

Older

ESMO

Older

"How I Treat"

NCCN

Antifungal prophylaxis

Older

Upfront induction therapy, standard and older "fit" patients

7+3d (standard-dose)

Regimen variant #1, 700/135 (CI Ara-C)

Chemotherapy

Subsequent treatment

Regimen variant #2, 700/150 (CI Ara-C)

Chemotherapy

Regimen variant #3, 1120/120 (intermittent Ara-C)

Chemotherapy

Regimen variant #4, 1400/135 (CI Ara-C)

Chemotherapy

Subsequent treatment

References

7+3d (intermediate-dose)

Regimen variant #1, CI Ara-C (100 mg/m2)

Chemotherapy

Subsequent treatment

Regimen variant #2, CI Ara-C (200 mg/m2)

Chemotherapy

Supportive therapy

Subsequent treatment

References

7+3d (high-dose)

Regimen variant #1, 700/270

Chemotherapy

Subsequent treatment

Regimen variant #2, 1400/240

Chemotherapy

Regimen variant #3, 1400/270

Chemotherapy

Subsequent treatment

References

7+3d & GO

Regimen variant #1, split GO dosing

Chemotherapy

Antibody-drug conjugate therapy

Subsequent treatment

Regimen variant #2, single-day GO

Chemotherapy

Antibody-drug conjugate therapy

Subsequent treatment

References

7+3i

Regimen variant #1, 80/12, intermittent Ara-C

Chemotherapy

Regimen variant #2, 100/12, CI Ara-C

Chemotherapy

Regimen variant #3, 100/13, CI Ara-C

Chemotherapy

Regimen variant #4, 200/12, CI Ara-C

Chemotherapy

Subsequent treatment

Regimen variant #5, with range

Chemotherapy

References

7+3i & Sorafenib

Regimen

Chemotherapy

Targeted therapy

Subsequent treatment

References

7+3d & Glasdegib

Regimen

Chemotherapy

Targeted therapy

Subsequent treatment

References

7+3m

Regimen variant #1, CI Ara-C (100 mg/m²)

Regimen variant #2, CI Ara-C (200 mg/m²)

Regimen variant #1, 50 mg/m² dauno

Regimen variant #2, 60 mg/m² dauno