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Induction therapy (APL, acute promyelocytic leukemia)

APL 2000 (EAPLG) induction

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 on days 3-5
Cytarabine (Cytosar) 200 mg/m2 IV on days 3-9

9-day course of initial induction chemotherapy, with ongoing use of ATRA

If >60 years old and WBC <10 x 10^9/L:

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 on days 3-5

To be followed by APL 2000 (EAPLG) consolidation therapy.

References

Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. link to original article contains protocol PubMed
Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. link to original article contains protocol PubMed

North American Leukemia Intergroup Study C9710 induction

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 on days 3-6
Cytarabine (Cytosar) 200 mg/m2/day IV continuous infusion on days 3-9

9-day initial induction chemotherapy, with ongoing use of ATRA

To be followed by North American Leukemia Intergroup Study C9710 consolidation therapy.

References

Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. link to original article contains protocol PubMed

AIDA 0493 induction

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 0493 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

PETHEMA LPA99, LPA2005 induction

PETHEMA: Programa Español de Tratamientos en HEMAtología

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 bolus on days 2, 4, 6, 8
- For patients >70 years old, Idarubicin (Idamycin) 12 mg/m2 IV bolus on days 2, 4, 6 (day 8 dose omitted)

8-day initial induction chemotherapy, with ongoing use of ATRA

To be followed by PETHEMA LPA99 or PETHEMA LPA2005 consolidation therapy.

References

Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. link to original article contains protocol PubMed
Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. 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)

APL 2000 (EAPLG) consolidation

Preceded by APL 2000 (EAPLG) induction therapy.

Consolidation regimen for patients ≤60 years old and WBC <10 x 10^9/L or age >60 and WBC >10 x 10^9/L

Daunorubicin (Cerubidine) 60 mg/m2 IV on days 1-3
Cytarabine (Cytosar) 200 mg/m2 IV on days 1-7

Followed by:

Daunorubicin (Cerubidine) 45 mg/m2 IV on days 1-3
Cytarabine (Cytosar) 1000 mg/m2 IV every 12 hours on days 1-4 (8 total doses)

Note: Adès, et al. 2006 and Adès, et al. 2008 both do not say that IT chemotherapy is used for patients with age >60 and WBC >10 x 10^9/L, but figure 1 in Adès, et al. 2006 depicts IT chemotherapy in this patient group. I did not see a reference that clearly resolved this contradiction.

Consolidation regimen for patients ≤60 years old and WBC >10 x 10^9/L

Daunorubicin (Cerubidine) 60 mg/m2 IV on days 1-3
Cytarabine (Cytosar) 200 mg/m2 IV on days 1-7
3 doses of intrathecal chemotherapy with Methotrexate (MTX) 15 mg IT, Cytarabine (Cytosar) 50 mg IT, and corticosteroids

Followed by:

Daunorubicin (Cerubidine) 45 mg/m2 IV on days 1-3
If age <50 years old: Cytarabine (Cytosar) 2000 mg/m2 IV every 12 hours on days 1-5 (10 total doses)
If age 50-60 years old: Cytarabine (Cytosar) 1500 mg/m2 IV every 12 hours on days 1-5 (10 total doses)
2 doses of intrathecal chemotherapy with Methotrexate (MTX) 15 mg IT, Cytarabine (Cytosar) 50 mg IT, and corticosteroids

Consolidation regimen for patients >60 years old and WBC <10 x 10^9/L

Daunorubicin (Cerubidine) 60 mg/m2 IV on days 1-3

Followed by:

Daunorubicin (Cerubidine) 45 mg/m2 IV on days 1-3

To be followed by APL 2000 (EAPLG) maintenance therapy.

References

Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. link to original article contains protocol PubMed
Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. link to original article contains protocol PubMed

North American Leukemia Intergroup Study C9710 consolidation

Preceded by North American Leukemia Intergroup Study C9710 induction therapy.

Regimen

Consolidation therapy starts within 2-4 weeks of hematologic remission:

Arsenic trioxide (Trisenox) 0.15 mg/kg IV days 1-5, 8-12, 15-19, 22-26, 29-33

7-week cycles (5 weeks of therapy, then 2 weeks off), 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 North American Leukemia Intergroup Study C9710 maintenance therapy.

References

Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. link to original article contains protocol PubMed

AIDA 0493 consolidation

AIDA: ATRA, IDArubicin
Preceded by AIDA 0493 induction therapy.

Regimen

As detailed in Avvisati, et al., 2002:

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 SC 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 AIDA 0493 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

PETHEMA LPA99 consolidation

PETHEMA: Programa Español de Tratamientos en HEMAtología
Preceded by PETHEMA LPA99, LPA2005 induction therapy.

Regimen

High risk:

All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
Idarubicin (Idamycin) 7 mg/m2 IV days 1-4

1-month 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

1-month 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 days 1 & 2

1-month cycle

Intermediate risk:

All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
Idarubicin (Idamycin) 7 mg/m2 IV days 1-4

1-month 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

1-month 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 days 1 & 2

1-month cycle

Low risk:

Idarubicin (Idamycin) 5 mg/m2 IV days 1-4

1-month cycle, THEN

Mitoxantrone (Novantrone) 10 mg/m2 IV days 1-5

1-month cycle, THEN

Idarubicin (Idamycin) 12 mg/m2 IV day 1

1-month cycle

To be followed by PETHEMA LPA99, LPA2005 maintenance therapy.

References

Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. link to original article contains protocol PubMed
Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. link to original article contains protocol PubMed

PETHEMA LPA2005 consolidation

PETHEMA: Programa Español de Tratamientos en HEMAtología
Preceded by PETHEMA LPA99, LPA2005 induction therapy.

Regimen

High risk:

All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
Idarubicin (Idamycin) 5 mg/m2 IV days 1-4
Cytarabine (Cytosar) 1000 mg/m2 IV days 1-4

1-month 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

1-month 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) 150 mg/m2, IV every 8 hours (total dose of 450 mg/m2/day), days 1-4 (12 total doses)

1-month cycle

Intermediate risk:

All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
Idarubicin (Idamycin) 7 mg/m2 IV days 1-4

1-month 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 1-3

1-month 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 days 1 & 2

1-month cycle

Low risk:

All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
Idarubicin (Idamycin) 5 mg/m2 IV days 1-4

1-month 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 1-3

1-month 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

1-month cycle

To be followed by PETHEMA LPA99, LPA2005 maintenance therapy.

References

Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. link to original article contains protocol PubMed
Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. link to original article contains protocol PubMed

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

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)

APL 2000 (EAPLG) maintenance

Preceded by APL 2000 (EAPLG) consolidation therapy.

Regimen

Mercaptopurine (Purinethol) 50-90 mg/m2 PO daily
Methotrexate (MTX) 15 mg/m2 PO weekly
All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1-15

90-day cycles x 2 years

References

Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. link to original article contains protocol PubMed
Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. link to original article contains protocol PubMed

North American Leukemia Intergroup Study C9710 maintenance

Preceded by North American Leukemia Intergroup Study C9710 consolidation therapy.

Regimen

Maintenance therapy starts 2-4 weeks after recovery from consolidation therapy:

All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID x 7 days every other week

With or without:

Mercaptopurine (Purinethol) 60 mg/m2 PO daily
Methotrexate (MTX) 20 mg/m2 PO weekly

1 year of therapy

References

Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. link to original article contains protocol PubMed

AIDA 0493 maintenance

Preceded by AIDA 0493 consolidation therapy.

Regimen

See Avvisati, et al. 2011 for details about outcomes with or without maintenance therapy. Treatment options investigated included only using Part A, only using Part B, or alternating between the two, in all cases for a total of 2 years.
Part A:

Mercaptopurine (Purinethol) 90 mg/m2 PO daily
Methotrexate (MTX) 15 mg/m2 IM weekly

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 regimen (Avvisati, et al. 2002)

Mercaptopurine (Purinethol) 1 mg/kg PO daily
Methotrexate (MTX) 0.25 mg/kg IM weekly

2-year course of 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
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
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 original article contains protocol PubMed

PETHEMA LPA99, LPA2005 maintenance

PETHEMA: Programa Español de Tratamientos en HEMAtología
Preceded by PETHEMA LPA99 or PETHEMA LPA2005 consolidation therapy.

Regimen

All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
Mercaptopurine (Purinethol) 50 mg/m2 PO daily
Methotrexate (MTX) 15 mg/m2 IM weekly

90-day cycles x 2 years

References

Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. link to original article contains protocol PubMed
Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. link to original article 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, Wrzesien'-Kus' A, Lech-Maran'da E, Kowal M, Dmoszyn'ska 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, Ho?owiecki J, Kyrcz-Krzemien' S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kie?bin'ski M, Zawilska K, K?oczko J, Wrzesien'-Kus' 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

@@ Line 5: / Line 5: @@
 {{TOC limit|limit=3}}
-==Induction therapy (APL, acute promyelocytic leukemia)==
+=Induction therapy (APL, acute promyelocytic leukemia)=
-===APL 2000 (EAPLG) induction===
+==APL 2000 (EAPLG) induction==
-====Regimen====
+===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 on days 3-5
@@ Line 20: / Line 20: @@
 To be followed by [[#APL_2000_.28EAPLG.29_consolidation|APL 2000 (EAPLG) consolidation]] therapy.
-====References====
+===References===
 # Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. [http://jco.ascopubs.org/content/24/36/5703.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17116939 PubMed]
 # Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://bloodjournal.hematologylibrary.org/content/111/3/1078.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17975017 PubMed]
-===North American Leukemia Intergroup Study C9710 induction===
+==North American Leukemia Intergroup Study C9710 induction==
-====Regimen====
+===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 on days 3-6
@@ Line 34: / Line 34: @@
 To be followed by [[#North_American_Leukemia_Intergroup_Study_C9710_consolidation|North American Leukemia Intergroup Study C9710 consolidation]] therapy.
-====References====
+===References===
 # Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://bloodjournal.hematologylibrary.org/content/116/19/3751.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20705755 PubMed]
-===AIDA 0493 induction===
+==AIDA 0493 induction==
 AIDA: '''<u>A</u>'''TRA, '''<u>IDA</u>'''rubicin
-====Regimen====
+===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
@@ Line 49: / Line 49: @@
 To be followed by [[#AIDA_0493_consolidation|AIDA 0493 consolidation]] therapy.
-====References====
+===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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08593.x/full link to full article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21751984 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. [http://bloodjournal.hematologylibrary.org/content/117/18/4716.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21385856 PubMed]
-===PETHEMA LPA99, LPA2005 induction===
+==PETHEMA LPA99, LPA2005 induction==
 PETHEMA: '''<u>P</u>'''rograma '''<u>E</u>'''spañol de '''<u>T</u>'''ratamientos en '''<u>HEMA</u>'''tología
-====Regimen====
+===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
@@ Line 65: / Line 65: @@
 To be followed by [[#PETHEMA_LPA99_consolidation|PETHEMA LPA99]] or [[#PETHEMA_LPA2005_consolidation|PETHEMA LPA2005]] consolidation therapy.
-====References====
+===References===
 # Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://bloodjournal.hematologylibrary.org/content/103/4/1237.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14576047 PubMed]
 # Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. [http://bloodjournal.hematologylibrary.org/content/115/25/5137.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20393132 PubMed]
-===ATRA & arsenic===
+==ATRA & arsenic==
-====Regimen====
+===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.
@@ Line 81: / Line 81: @@
 *[[Arsenic trioxide (Trisenox)]] 0.16 mg/kg IV daily, starting day 1 and continuing until remission
-====References====
+===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. [http://www.pnas.org/content/101/15/5328.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15044693 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. [http://bloodjournal.hematologylibrary.org/content/107/9/3469.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16373661 PubMed]
-==Induction therapy (AML, acute myeloid leukemia)==
+=Induction therapy (AML, acute myeloid leukemia)=
-===7+3 Cytarabine (Cytosar) & Idarubicin (Idamycin)===
+==7+3 Cytarabine (Cytosar) & Idarubicin (Idamycin)==
-====Regimen====
+===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
@@ Line 93: / Line 93: @@
 '''7-day course'''
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/79/2/313.abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/1730080 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. [http://www.ncbi.nlm.nih.gov/pubmed/8290968 PubMed]
@@ Line 100: / Line 100: @@
 # 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. [http://bloodjournal.hematologylibrary.org/content/115/3/453.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19880497 PubMed]
-===7+3 Cytarabine (Cytosar) & Daunorubicin (Cerubidine)===
+==7+3 Cytarabine (Cytosar) & Daunorubicin (Cerubidine)==
-====Regimen====
+===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
@@ Line 107: / Line 107: @@
 '''7-day course'''
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/69/5/1441.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/3552076 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. [http://bloodjournal.hematologylibrary.org/content/103/2/479.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14512295 PubMed]
@@ Line 113: / Line 113: @@
 # 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. [http://bloodjournal.hematologylibrary.org/content/115/3/453.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19880497 PubMed]
-===Decitabine (Dacogen) & Valproic acid===
+==Decitabine (Dacogen) & Valproic acid==
-====Regimen====
+===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
@@ Line 120: / Line 120: @@
 '''28-day cycles x up to 24 total cycles'''
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/108/10/3271.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16882711 PubMed]
-==Consolidation therapy (APL, acute promyelocytic leukemia)==
+=Consolidation therapy (APL, acute promyelocytic leukemia)=
-===APL 2000 (EAPLG) consolidation===
+==APL 2000 (EAPLG) consolidation==
 Preceded by [[#APL_2000_.28EAPLG.29_induction|APL 2000 (EAPLG) induction]] therapy.
-====Consolidation regimen for patients ≤60 years old and WBC <10 x 10^9/L or age >60 and WBC >10 x 10^9/L====
+===Consolidation regimen for patients ≤60 years old and WBC <10 x 10^9/L or age >60 and WBC >10 x 10^9/L===
 *[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1-3
 *[[Cytarabine (Cytosar)]] 200 mg/m2 IV on days 1-7
@@ Line 137: / Line 137: @@
 '''Note: Adès, et al. 2006 and Adès, et al. 2008 both do not say that IT chemotherapy is used for patients with age >60 and WBC >10 x 10^9/L, but figure 1 in Adès, et al. 2006 depicts IT chemotherapy in this patient group.  I did not see a reference that clearly resolved this contradiction.'''
-====Consolidation regimen for patients ≤60 years old and WBC >10 x 10^9/L====
+===Consolidation regimen for patients ≤60 years old and WBC >10 x 10^9/L===
 *[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1-3
 *[[Cytarabine (Cytosar)]] 200 mg/m2 IV on days 1-7
@@ Line 148: / Line 148: @@
 *2 doses of intrathecal chemotherapy with [[Methotrexate (MTX)]] 15 mg IT, [[Cytarabine (Cytosar)]] 50 mg IT, and corticosteroids
-====Consolidation regimen for patients >60 years old and WBC <10 x 10^9/L====
+===Consolidation regimen for patients >60 years old and WBC <10 x 10^9/L===
 *[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1-3
@@ Line 156: / Line 156: @@
 To be followed by [[#APL_2000_.28EAPLG.29_maintenance|APL 2000 (EAPLG) maintenance]] therapy.
-====References====
+===References===
 # Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. [http://jco.ascopubs.org/content/24/36/5703.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17116939 PubMed]
 # Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://bloodjournal.hematologylibrary.org/content/111/3/1078.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17975017 PubMed]
-===North American Leukemia Intergroup Study C9710 consolidation===
+==North American Leukemia Intergroup Study C9710 consolidation==
 Preceded by [[#North_American_Leukemia_Intergroup_Study_C9710_induction|North American Leukemia Intergroup Study C9710 induction]] therapy.
-====Regimen====
+===Regimen===
 Consolidation therapy starts within 2-4 weeks of hematologic remission:
 *[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV days 1-5, 8-12, 15-19, 22-26, 29-33
@@ Line 175: / Line 175: @@
 To be followed by [[#North_American_Leukemia_Intergroup_Study_C9710_maintenance|North American Leukemia Intergroup Study C9710 maintenance]] therapy.
-====References====
+===References===
 # Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://bloodjournal.hematologylibrary.org/content/116/19/3751.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20705755 PubMed]
-===AIDA 0493 consolidation===
+==AIDA 0493 consolidation==
 AIDA: '''<u>A</u>'''TRA, '''<u>IDA</u>'''rubicin <br>
 Preceded by [[#AIDA_0493_induction|AIDA 0493 induction]] therapy.
-====Regimen====
+===Regimen===
 As detailed in Avvisati, et al., 2002:
 *[[Idarubicin (Idamycin)]] 5 mg/m2 IV days 1-4 (administered second, 3 hours after cytarabine infusion complete)
@@ Line 201: / Line 201: @@
 To be followed by [[#AIDA_0493_maintenance|AIDA 0493 maintenance]] therapy.
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/100/9/3141.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12384411 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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08593.x/full link to full article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21751984 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. [http://bloodjournal.hematologylibrary.org/content/117/18/4716.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21385856 PubMed]
-===PETHEMA LPA99 consolidation===
+==PETHEMA LPA99 consolidation==
 PETHEMA: '''<u>P</u>'''rograma '''<u>E</u>'''spañol de '''<u>T</u>'''ratamientos en '''<u>HEMA</u>'''tología
 <br>Preceded by [[#PETHEMA_LPA99.2C_LPA2005_induction|PETHEMA LPA99, LPA2005 induction]] therapy.
-====Regimen====
+===Regimen===
 High risk:
 *[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
@@ Line 257: / Line 257: @@
 To be followed by [[#PETHEMA_LPA99.2C_LPA2005_maintenance|PETHEMA LPA99, LPA2005 maintenance]] therapy.
-====References====
+===References===
 # Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://bloodjournal.hematologylibrary.org/content/103/4/1237.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14576047 PubMed]
 # Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. [http://bloodjournal.hematologylibrary.org/content/115/25/5137.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20393132 PubMed]
-===PETHEMA LPA2005 consolidation===
+==PETHEMA LPA2005 consolidation==
 PETHEMA: '''<u>P</u>'''rograma '''<u>E</u>'''spañol de '''<u>T</u>'''ratamientos en '''<u>HEMA</u>'''tología
 <br>Preceded by [[#PETHEMA_LPA99.2C_LPA2005_induction|PETHEMA LPA99, LPA2005 induction]] therapy.
-====Regimen====
+===Regimen===
 High risk:
 *[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
@@ Line 317: / Line 317: @@
 To be followed by [[#PETHEMA_LPA99.2C_LPA2005_maintenance|PETHEMA LPA99, LPA2005 maintenance]] therapy.
-====References====
+===References===
 # Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://bloodjournal.hematologylibrary.org/content/103/4/1237.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14576047 PubMed]
 # Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. [http://bloodjournal.hematologylibrary.org/content/115/25/5137.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20393132 PubMed]
-===ATRA & arsenic - consolidation===
+==ATRA & arsenic - consolidation==
 Preceded by [[#ATRA_.26_arsenic|ATRA & arsenic]] induction therapy.
-====Regimen====
+===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
@@ Line 329: / Line 329: @@
 '''28 weeks of therapy'''
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/107/9/3469.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16373661 PubMed]
-==Consolidation therapy (AML, acute myeloid leukemia)==
+=Consolidation therapy (AML, acute myeloid leukemia)=
-===HiDAC/HDAC, high-dose Cytarabine (Cytosar)===
+==HiDAC/HDAC, high-dose Cytarabine (Cytosar)==
 HiDAC: '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>'''
-====Regimen====
+===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====
+===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. [http://www.nejm.org/doi/full/10.1056/NEJM199410063311402 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8078551 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. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22287757 PubMed]
-===MiDAC/MDAC, mid-dose Cytarabine (Cytosar)===
+==MiDAC/MDAC, mid-dose Cytarabine (Cytosar)==
 MiDAC: '''<u>Mi</u>'''d '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>'''
-====Regimen====
+===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====
+===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. [http://ar.iiarjournals.org/content/32/2/643.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22287757 PubMed]
-===Cytarabine (Cytosar) & Daunorubicin (Cerubidine), ambulatory===
+==Cytarabine (Cytosar) & Daunorubicin (Cerubidine), ambulatory==
-====Regimen====
+===Regimen===
 *[[Cytarabine (Cytosar)]] 60 mg/m2 SC Q12H on days 1-5 (10 total doses)
 *[[Daunorubicin (Cerubidine)]] 45 mg/m2 IV on day 1
@@ Line 363: / Line 363: @@
 '''1-month cycles x up to 6 cycles'''
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/109/12/5129.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17341661 PubMed]
-==Maintenance therapy (APL, acute promyelocytic leukemia)==
+=Maintenance therapy (APL, acute promyelocytic leukemia)=
-===APL 2000 (EAPLG) maintenance===
+==APL 2000 (EAPLG) maintenance==
 Preceded by [[#APL_2000_.28EAPLG.29_consolidation|APL 2000 (EAPLG) consolidation]] therapy.
-====Regimen====
+===Regimen===
 *[[Mercaptopurine (Purinethol)]] 50-90 mg/m2 PO daily
 *[[Methotrexate (MTX)]] 15 mg/m2 PO weekly
@@ Line 377: / Line 377: @@
 '''90-day cycles x 2 years'''
-====References====
+===References===
 # Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. [http://jco.ascopubs.org/content/24/36/5703.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17116939 PubMed]
 # Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://bloodjournal.hematologylibrary.org/content/111/3/1078.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17975017 PubMed]
-===North American Leukemia Intergroup Study C9710 maintenance===
+==North American Leukemia Intergroup Study C9710 maintenance==
 Preceded by [[#North_American_Leukemia_Intergroup_Study_C9710_consolidation|North American Leukemia Intergroup Study C9710 consolidation]] therapy.
-====Regimen====
+===Regimen===
 Maintenance therapy starts 2-4 weeks after recovery from consolidation therapy:
 *[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID x 7 days every other week
@@ Line 392: / Line 392: @@
 '''1 year of therapy'''
-====References====
+===References===
 # Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://bloodjournal.hematologylibrary.org/content/116/19/3751.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20705755 PubMed]
-===AIDA 0493 maintenance===
+==AIDA 0493 maintenance==
 Preceded by [[#AIDA_0493_consolidation|AIDA 0493 consolidation]] therapy.
-====Regimen====
+===Regimen===
 ''See Avvisati, et al. 2011 for details about outcomes with or without maintenance therapy.  Treatment options investigated included only using Part A, only using Part B, or alternating between the two, in all cases for a total of 2 years.''
 <br>Part A:
@@ Line 410: / Line 410: @@
 '''15-day course of therapy'''
-====Alternate regimen (Avvisati, et al. 2002)====
+===Alternate regimen (Avvisati, et al. 2002)===
 *[[Mercaptopurine (Purinethol)]] 1 mg/kg PO daily
 *[[Methotrexate (MTX)]] 0.25 mg/kg IM weekly
@@ Line 416: / Line 416: @@
 '''2-year course of therapy'''
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/100/9/3141.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12384411 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. [http://bloodjournal.hematologylibrary.org/content/117/18/4716.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21385856 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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08593.x/full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21751984 PubMed]
-===PETHEMA LPA99, LPA2005 maintenance===
+==PETHEMA LPA99, LPA2005 maintenance==
 PETHEMA: '''<u>P</u>'''rograma '''<u>E</u>'''spañol de '''<u>T</u>'''ratamientos en '''<u>HEMA</u>'''tología
 <br>Preceded by [[#PETHEMA_LPA99_consolidation|PETHEMA LPA99]] or [[#PETHEMA_LPA2005_consolidation|PETHEMA LPA2005]] consolidation therapy.
-====Regimen====
+===Regimen===
 *[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
 *[[Mercaptopurine (Purinethol)]] 50 mg/m2 PO daily
@@ Line 431: / Line 431: @@
 '''90-day cycles x 2 years'''
-====References====
+===References===
 # Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://bloodjournal.hematologylibrary.org/content/103/4/1237.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14576047 PubMed]
 # Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. [http://bloodjournal.hematologylibrary.org/content/115/25/5137.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20393132 PubMed]
-==Salvage therapy (AML, acute myeloid leukemia)==
+=Salvage therapy (AML, acute myeloid leukemia)=
-===ADE===
+==ADE==
 ADE: '''<u>A</u>'''ra-C, '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide
-====Regimen====
+===Regimen===
 Course 1
 *[[Cytarabine (Cytosar)]] 100 mg/m2 IV push Q12H on days 1-10 (20 total doses)
@@ Line 449: / Line 449: @@
 *[[Etoposide (Vepesid)]] 100 mg/m2 IV over 1 hour on days 1-5 (5 total doses)
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/107/12/4614.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16484584 PubMed]
-===Azacitidine (Vidaza)===
+==Azacitidine (Vidaza)==
-====Regimen====
+===Regimen===
 *[[Azacitidine (Vidaza)]] 75 mg/m2 SC days 1-7
 '''28-day cycles x at least 4-6 cycles'''
-====References====
+===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. [http://bloodjournal.hematologylibrary.org/content/116/19/3735.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20664061 PubMed]
-===Cladribine (Leustatin)===
+==Cladribine (Leustatin)==
-====Regimen====
+===Regimen===
 *[[Cladribine (Leustatin)]] 8.9 mg/m2/day IV continuous infusion on days 1-5
-====References====
+===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. [http://jco.ascopubs.org/content/10/3/364.abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/1346800 PubMed]
-===CLAG===
+==CLAG==
 CLAG: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C, '''<u>G</u>'''-CSF
-====Regimen====
+===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====
+===References===
 # Robak T, Wrzesien'-Kus' A, Lech-Maran'da E, Kowal M, Dmoszyn'ska 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. [http://informahealthcare.com/doi/abs/10.3109/10428190009053545 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10975390 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. [http://www.ncbi.nlm.nih.gov/pubmed/19717379 PubMed]
-===CLAG-M, CLAM===
+==CLAG-M, CLAM==
 CLAG-M: '''<u>CL</u>'''adribine, '''<u>A</u>'''ra-C, '''<u>G</u>'''-CSF, '''<u>M</u>'''itoxantrone
-====Regimen====
+===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)
@@ Line 487: / Line 487: @@
 *[[Filgrastim (Neupogen)]] 300 mcg SC on days 0-5 (first dose 24 hours before first dose of cladribine)
-====References====
+===References===
 # Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Ho?owiecki J, Kyrcz-Krzemien' S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kie?bin'ski M, Zawilska K, K?oczko J, Wrzesien'-Kus' 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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2007.00988.x/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18076637 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. [http://www.ncbi.nlm.nih.gov/pubmed/19717379 PubMed]
-===FLAG===
+==FLAG==
 FLAG: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C, '''<u>G</u>'''-CSF
-====Regimen====
+===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====
+===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. [http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291096-8652%28199806%2958:2%3C105::AID-AJH3%3E3.0.CO;2-W/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/9625576 PubMed]
-===FLAG-IDA===
+==FLAG-IDA==
 FLAG-IDA: '''<u>FL</u>'''udarabine, '''<u>A</u>'''ra-C, '''<u>G</u>'''-CSF, '''<u>IDA</u>'''rubicin
-====Regimen====
+===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)
@@ Line 509: / Line 509: @@
 *[[Filgrastim (Neupogen)]] 5 mcg/kg SC starting on day 6, to continue until neutrophil recovery
-====References====
+===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. [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.springerlink.com/content/0gg2unjwywej9tg5/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12707726 PubMed]
-===Mitoxantrone (Novantrone) & Cytarabine (Cytosar)===
+==Mitoxantrone (Novantrone) & Cytarabine (Cytosar)==
-====Regimen====
+===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====
+===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. [http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291097-0142%2820000501%2988:9%3C2037::AID-CNCR8%3E3.0.CO;2-K/full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10813714 PubMed]
-===Mitoxantrone (Novantrone) & Etoposide (Vepesid)===
+==Mitoxantrone (Novantrone) & Etoposide (Vepesid)==
-====Regimen====
+===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====
+===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. [http://jco.ascopubs.org/content/6/2/213.abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/3422260 PubMed]
-===MEC===
+==MEC==
 MEC: '''<u>M</u>'''itoxantrone, '''<u>E</u>'''toposide, '''<u>C</u>'''ytarabine
-====Regimen====
+===Regimen===
 Regimen #1 (Amadori, et al. 1991)
 *[[Mitoxantrone (Novantrone)]] 6 mg/m2 IV bolus on days 1-6
@@ Line 542: / Line 542: @@
 *[[Cytarabine (Cytosar)]] 1000 mg/m2 IV on days 1-5 (administered second)
-====References====
+===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. [http://jco.ascopubs.org/content/9/7/1210.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/2045861 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. [http://onlinelibrary.wiley.com/doi/10.1002/ajh.21857/full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20872554 PubMed]

Difference between revisions of "Acute myeloid leukemia"

Revision as of 00:37, 21 April 2012

Induction therapy (APL, acute promyelocytic leukemia)

APL 2000 (EAPLG) induction

Regimen

References

North American Leukemia Intergroup Study C9710 induction

Regimen

References

AIDA 0493 induction

Regimen

References

PETHEMA LPA99, LPA2005 induction

Regimen

References

ATRA & arsenic

Regimen

References

Induction therapy (AML, acute myeloid leukemia)

7+3 Cytarabine (Cytosar) & Idarubicin (Idamycin)

Regimen

References

7+3 Cytarabine (Cytosar) & Daunorubicin (Cerubidine)

Regimen

References

Decitabine (Dacogen) & Valproic acid

Regimen

References

Consolidation therapy (APL, acute promyelocytic leukemia)

APL 2000 (EAPLG) consolidation

Consolidation regimen for patients ≤60 years old and WBC <10 x 10^9/L or age >60 and WBC >10 x 10^9/L

Consolidation regimen for patients ≤60 years old and WBC >10 x 10^9/L

Consolidation regimen for patients >60 years old and WBC <10 x 10^9/L

References

North American Leukemia Intergroup Study C9710 consolidation

Regimen

References

AIDA 0493 consolidation

Regimen

References

PETHEMA LPA99 consolidation

Regimen

References

PETHEMA LPA2005 consolidation

Regimen

References

ATRA & arsenic - consolidation

Regimen

References

Consolidation therapy (AML, acute myeloid leukemia)

HiDAC/HDAC, high-dose Cytarabine (Cytosar)

Regimen

References

MiDAC/MDAC, mid-dose Cytarabine (Cytosar)

Regimen

References

Cytarabine (Cytosar) & Daunorubicin (Cerubidine), ambulatory

Regimen

References

Maintenance therapy (APL, acute promyelocytic leukemia)

APL 2000 (EAPLG) maintenance

Regimen

References

North American Leukemia Intergroup Study C9710 maintenance

Regimen

References

AIDA 0493 maintenance

Regimen

Alternate regimen (Avvisati, et al. 2002)

References

PETHEMA LPA99, LPA2005 maintenance

Regimen

References

Salvage therapy (AML, acute myeloid leukemia)

ADE

Regimen

References

Azacitidine (Vidaza)

Regimen

References