Acute myeloid leukemia
Induction therapy (APL, acute promyelocytic leukemia)
ATRA, Daunorubicin, Cytarabine #1
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- Daunorubicin (Cerubidine) 60 mg/m2 IV days 1-3
- Cytarabine (Cytosar) 200 mg/m2 IV days 1-7
7-day initial induction chemotherapy, with ongoing use of ATRA
To be followed by Daunorubicin, Cytarabine, IT chemo consolidation therapy.
References
ATRA, Daunorubicin, Cytarabine #2
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- Daunorubicin (Cerubidine) 50 mg/m2 IV days 1-4
- Cytarabine (Cytosar) 200 mg/m2 IV days 1-7
7-day initial induction chemotherapy, with ongoing use of ATRA
To be followed by Arsenic, ATRA, Daunorubicin consolidation therapy.
References
AIDA
AIDA: ATRA, IDArubicin
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- For patients <20 years old, All-trans retinoic acid (ATRA) dose was 25 mg/m2/day, divided into two equal doses PO BID
- Idarubicin (Idamycin) 12 mg/m2 IV days 2, 4, 6, 8
8-day initial induction chemotherapy, with ongoing use of ATRA
To be followed by AIDA consolidation therapy or ATRA, idarubicin, cytarabine, mitoxantrone consolidation therapy.
References
- Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to full article contains protocol PubMed
- Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains protocol PubMed
ATRA & arsenic
Regimen
Estey 2006:
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 1 hour daily, starting day 11 and continuing until remission
To be followed by ATRA & arsenic consolidation therapy.
Alternate regimen (Shen 2004):
- All-trans retinoic acid (ATRA) 25 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- Arsenic trioxide (Trisenox) 0.16 mg/kg IV daily, starting day 1 and continuing until remission
References
- Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang ZY, Chen SJ, Chen Z. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5328-35. Epub 2004 Mar 24. link to original article contains protocol PubMed
- Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006 May 1;107(9):3469-73. Epub 2005 Dec 22. link to original article contains protocol PubMed
Induction therapy (AML, acute myeloid leukemia)
7+3 Cytarabine (Cytosar) & Idarubicin (Idamycin)
Regimen
- Cytarabine (Cytosar) 100-200 mg/m2/day IV continuous infusion on days 1-7
- Idarubicin (Idamycin) 12 mg/m2 IV on days 1-3
7-day course
References
- 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 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. PubMed
- 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 protocol PubMed
- Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. Epub 2009 Oct 30. link to original article contains protocol PubMed
7+3 Cytarabine (Cytosar) & Daunorubicin (Cerubidine)
Regimen
- Cytarabine (Cytosar) 100-200 mg/m2/day IV continuous infusion on days 1-7
- Daunorubicin (Cerubidine) 45-90 mg/m2 IV on days 1-3
7-day course
References
- Preisler H, Davis RB, Kirshner J, Dupre E, Richards F 3rd, Hoagland HC, Kopel S, Levy RN, Carey R, Schulman P, et al. 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 protocol PubMed
- 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 protocol PubMed
- 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 protocol PubMed
- Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. Epub 2009 Oct 30. link to original article contains protocol PubMed
Decitabine (Dacogen) & Valproic acid
Regimen
- Decitabine (Dacogen) 15 mg/m2 IV over 1 hour on days 1-10
- Valproic acid 50 mg/kg/day (divided in 2 or 3 doses per day) PO on days 1-10
28-day cycles x up to 24 total cycles
References
- Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, Yang H, Rosner G, Verstovsek S, Rytting M, Wierda WG, Ravandi F, Koller C, Xiao L, Faderl S, Estrov Z, Cortes J, O'brien S, Estey E, Bueso-Ramos C, Fiorentino J, Jabbour E, Issa JP. Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia. Blood. 2006 Nov 15;108(10):3271-9. Epub 2006 Aug 1. link to original article contains protocol PubMed
Consolidation therapy (APL, acute promyelocytic leukemia)
Daunorubicin, Cytarabine, IT chemo
Preceded by ATRA, Daunorubicin, Cytarabine #1 induction therapy.
Regimen
- Daunorubicin (Cerubidine) 60 mg/m2 IV on days 1-3
- Cytarabine (Cytosar) 200 mg/m2 IV on days 1-7
7 days of therapy, THEN
- Daunorubicin (Cerubidine) 45 mg/m2 IV on days 1-3
- Cytarabine (Cytosar) 1500-2000 mg/m2 IV every 12 hours on days 1-7
- 5 doses of intrathecal chemotherapy
7 days of therapy
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
Arsenic, ATRA, Daunorubicin
Preceded by ATRA, Daunorubicin, Cytarabine #2 induction therapy.
Regimen
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV days 1-5, 8-12, 15-19, 22-26, 29-33
5-week cycles x 2 cycles, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting days 1-7
- Daunorubicin (Cerubidine) 50 mg/m2 IV days 1-3
7-day cycles x 2 cycles
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
AIDA - consolidation therapy
AIDA: ATRA, IDArubicin
Preceded by AIDA induction therapy.
Regimen
- Idarubicin (Idamycin) 5 mg/m2 IV days 1-4 (administered second, 3 hours after cytarabine infusion complete)
- Cytarabine (Cytosar) 1000 mg/m2 IV over 6 hours on days 1-4 (administered first)
4-day course of therapy, THEN
- Mitoxantrone (Novantrone) 10 mg/m2 IV days 1-5 (administered first)
- Etoposide (Vepesid) 100 mg/m2 IV over 45-60 minutes (administered second, 12 hours after start of mitoxantrone) days 1-5
5-day course of therapy, THEN
- Idarubicin (Idamycin) 12 mg/m2 IV day 1
- Cytarabine (Cytosar) 150 mg/m2 IV every 8 hours (450 mg/m2/day total dosage) days 1-5
- Thioguanine (Tabloid) 70 mg/m2 PO every 8 hours (210 mg/m2/day total dosage) days 1-5
5-day course of therapy
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
- Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA (Gruppo Italiano Malattie Ematologische dell'Adulto) Italian Cooperative Group. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. link to original article contains protocol PubMed
- Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to full article contains protocol PubMed
- Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains protocol PubMed
ATRA, idarubicin, cytarabine, mitoxantrone
Preceded by AIDA induction therapy.
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
- Idarubicin (Idamycin) 5-7 mg/m2 IV days 1-4 -- 5 mg/m2 dosage used for low risk patients, 7 mg/m2 dosage used for intermediate risk patients
- Cytarabine (Cytosar) 1000 mg/m2 IV days 1-4
15-day cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
- Mitoxantrone (Novantrone) 10 mg/m2 IV days 1-5
15-day cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
- Idarubicin (Idamycin) 12 mg/m2 IV day 1
- Cytarabine (Cytosar) 450 mg/m2, divided into three equal doses IV every 8 hours, days 1-4
15-day cycle
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
ATRA & arsenic - consolidation
Preceded by ATRA & arsenic induction therapy.
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, 7 days per week on weeks 1-2, 5-6, 9-10, 13-14, 17-18, 21-22, 25-26
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 1 hour daily, 5 consecutive days per week on weeks 1-4, 9-12, 17-20, 25-28
28 weeks of therapy
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
- Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006 May 1;107(9):3469-73. Epub 2005 Dec 22. link to original article contains protocol PubMed
Consolidation therapy (AML, acute myeloid leukemia)
HiDAC/HDAC, high-dose Cytarabine (Cytosar)
HiDAC: High Dose Ara-C
Regimen
- Cytarabine (Cytosar) 2000-3000 mg/m2 IV over 3 hours Q12H on days 1, 3, 5 (6 total doses)
28-day (minimum) cycles or 1 week after marrow recovery, whichever comes later x up to 4 cycles
References
- Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994 Oct 6;331(14):896-903. link to original article contains protocol PubMed
- 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 protocol PubMed
MiDAC/MDAC, mid-dose Cytarabine (Cytosar)
MiDAC: Mid Dose Ara-C
Regimen
- Cytarabine (Cytosar) 1000 mg/m2 IV over 1 hour Q12H on days 1-5 (10 total doses)
subsequent cycles started after marrow recovery
References
- 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 protocol PubMed
Cytarabine (Cytosar) & Daunorubicin (Cerubidine), ambulatory
Regimen
- Cytarabine (Cytosar) 60 mg/m2 SC Q12H on days 1-5 (10 total doses)
- Daunorubicin (Cerubidine) 45 mg/m2 IV on day 1
1-month cycles x up to 6 cycles
References
- 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 protocol PubMed
Maintenance therapy (APL, acute promyelocytic leukemia)
ATRA
AIDA: ATRA, IDArubicin
Preceded by APL consolidation therapies.
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
3-month cycles x 2 years (8 total cycles)
References
- Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA (Gruppo Italiano Malattie Ematologische dell'Adulto) Italian Cooperative Group. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. link to original article contains protocol PubMed
- Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to full article contains protocol PubMed
- Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains protocol PubMed
Mercaptopurine, Methotrexate, alternating with ATRA
AIDA: ATRA, IDArubicin
Preceded by APL consolidation therapies.
Regimen
Part A:
- Mercaptopurine (Purinethol) 1 mg/kg PO daily
- Methotrexate (MTX) 15 mg/m2 OR 0.25 mg/kg IM weekly -- papers below list different dosages
90-day course of therapy, THEN
Part B:
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
15-day course of therapy. Alternate between Part A and Part B for a total of 2 years
References
- Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA (Gruppo Italiano Malattie Ematologische dell'Adulto) Italian Cooperative Group. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. link to original article contains protocol PubMed
- Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains protocol PubMed
Salvage therapy (AML, acute myeloid leukemia)
ADE
ADE: Ara-C, Daunorubicin, Etoposide
Regimen
Course 1
- Cytarabine (Cytosar) 100 mg/m2 IV push Q12H on days 1-10 (20 total doses)
- Daunorubicin (Cerubidine) 50 mg/m2 IV slow push on days 1, 3, 5 (3 total doses)
- Etoposide (Vepesid) 100 mg/m2 IV over 1 hour on days 1-5 (5 total doses)
Course 2
- Cytarabine (Cytosar) 100 mg/m2 IV push Q12H on days 1-8 (16 total doses)
- Daunorubicin (Cerubidine) 50 mg/m2 IV slow push on days 1, 3, 5 (3 total doses)
- Etoposide (Vepesid) 100 mg/m2 IV over 1 hour on days 1-5 (5 total doses)
References
- 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
Azacitidine (Vidaza)
Regimen
- Azacitidine (Vidaza) 75 mg/m2 SC days 1-7
28-day cycles x at least 4-6 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 (GFM). 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
Cladribine (Leustatin)
Regimen
- Cladribine (Leustatin) 8.9 mg/m2/day IV continuous infusion on days 1-5
References
- Santana VM, Mirro J Jr, Kearns C, Schell MJ, Crom W, Blakley RL. 2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia. J Clin Oncol. 1992 Mar;10(3):364-70. link to original article PubMed
CLAG
CLAG: CLadribine, Ara-C, G-CSF
Regimen
- Cladribine (Leustatin) 5 mg/m2/day IV over 2 hours on days 1-5 (administered first)
- Cytarabine (Cytosar) 2000 mg/m2/day IV over 4 hours on days 1-5 (administered second, 2 hours after cladribine)
- Filgrastim (Neupogen) 300 mcg SC on days 0-5 (first dose 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 protocol PubMed
- 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, CLAM
CLAG-M: CLadribine, Ara-C, G-CSF, Mitoxantrone
Regimen
- Cladribine (Leustatin) 5 mg/m2/day IV over 2 hours on days 1-5 (administered first)
- Cytarabine (Cytosar) 2000 mg/m2/day IV over 4 hours on days 1-5 (administered second, 2 hours after cladribine)
- Mitoxantrone (Novantrone) 10 mg/m2/day IV on days 1-3
- Filgrastim (Neupogen) 300 mcg SC on days 0-5 (first dose 24 hours before first dose of cladribine)
References
- Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Hołowiecki J, Kyrcz-Krzemień S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kiełbiński M, Zawilska K, Kłoczko 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 PubMed
- 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
FLAG
FLAG: FLudarabine, Ara-C, G-CSF
Regimen
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes on days 1-5 (administered first)
- Cytarabine (Cytosar) 2000 mg/m2 IV over 4 hours on days 1-5 (administered second, 4 hours after the start of fludarabine)
- Filgrastim (Neupogen) 5 mcg/kg SC starting on day 0, to continue until neutrophil recovery
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 PubMed
FLAG-IDA
FLAG-IDA: FLudarabine, Ara-C, G-CSF, IDArubicin
Regimen
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes on days 1-5 (administered first)
- Cytarabine (Cytosar) 2000 mg/m2 IV over 4 hours on days 1-5 (administered second, 4 hours after fludarabine)
- Idarubicin (Idamycin) 10 mg/m2 IV on days 1-3
- Filgrastim (Neupogen) 5 mcg/kg SC starting on day 6, to continue until neutrophil recovery
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. 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 PubMed
Mitoxantrone (Novantrone) & Cytarabine (Cytosar)
Regimen
- Mitoxantrone (Novantrone) 5 mg/m2 IV bolus on days 1-5
- Cytarabine (Cytosar) 500 mg/m2 IV over 90 minutes, Q12H on days 1-6 (12 total doses)
References
- 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 protocol PubMed
Mitoxantrone (Novantrone) & Etoposide (Vepesid)
Regimen
- Mitoxantrone (Novantrone) 10 mg/m2 IV over 15 minutes on days 1-5
- Etoposide (Vepesid) 100 mg/m2 IV over 30 minutes on days 1-5
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
MEC
MEC: Mitoxantrone, Etoposide, Cytarabine
Regimen
Regimen #1 (Amadori, et al. 1991)
- Mitoxantrone (Novantrone) 6 mg/m2 IV bolus on days 1-6
- Etoposide (Vepesid) 80 mg/m2 IV over 1 hour on days 1-6
- Cytarabine (Cytosar) 1000 mg/m2 IV over 6 hours on days 1-6
Regimen #2 (Kohrt, et al. 2010)
- Mitoxantrone (Novantrone) 8 mg/m2 IV push on days 1-5 (administered third)
- Etoposide (Vepesid) 100 mg/m2 IV over 2 hours on days 1-5 (administered first)
- Cytarabine (Cytosar) 1000 mg/m2 IV on days 1-5 (administered second)
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
- Kohrt HE, Patel S, Ho M, Owen T, Pollyea DA, Majeti R, Gotlib J, Coutre S, Liedtke M, Berube C, Alizadeh AA, Medeiros BC. Second-line mitoxantrone, etoposide, and cytarabine for acute myeloid leukemia: a single-center experience. Am J Hematol. 2010 Nov;85(11):877-81. link to original article contains protocol PubMed