Acute myeloid leukemia

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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

1. 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 verified protocol PubMed
2. 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 verified 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

1. 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 verified 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

1. 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 verified protocol PubMed
2. 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 verified 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

1. 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 verified protocol PubMed
2. 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 verified protocol PubMed

Arsenic monotherapy

Regimen

• Arsenic trioxide (Trisenox) 10 mg (0.15 mg/kg for pediatric patients) IV over 2-3 hours daily

given until complete remission (CR) or maximum of 75 days (maximum of 60 days after 2001)

If in CR, wait 4 weeks, then:

• Arsenic trioxide (Trisenox) 10 mg (0.15 mg/kg for pediatric patients) IV over 2-3 hours daily x 28 days

28-day course

If in CR, wait 4 weeks, then:

• Arsenic trioxide (Trisenox) 10 mg (0.15 mg/kg for pediatric patients) IV over 2-3 hours daily x "10 days a month"

1-month cycles x 6 months

References

1. Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006 Apr 1;107(7):2627-32. Epub 2005 Dec 13. link to original article contains verified protocol PubMed
2. Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P,Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010 Aug 20;28(24):3866-71. doi: 10.1200/JCO.2010.28.5031. Epub 2010 Jul 19. link to original article 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

1. 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 verified protocol PubMed
2. 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 verified protocol PubMed

Induction therapy (AML, acute myeloid leukemia)

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

1. 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 verified protocol PubMed
2. 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 verified protocol PubMed
3. 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 verified protocol PubMed
4. 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 verified protocol PubMed

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

1. 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
2. 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
3. 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
4. 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 verified protocol PubMed
5. 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 verified protocol PubMed

Cytarabine (Cytosar), Idarubicin (Idamycin), Vorinostat (Zolinza) induction

Regimen

• Vorinostat (Zolinza) 500 mg PO TID on days 1-3
• Cytarabine (Cytosar) 1500 mg/m2/day IV continuous infusion on days 4-7
  • Patients older than 60 received: Cytarabine (Cytosar) 1500 mg/m2/day IV continuous infusion on days 4-6 instead
• Idarubicin (Idamycin) 12 mg/m2 IV on days 4-6

7-day course x 1-2 cycles

Supportive medications:

• Methylprednisolone (Solu-Medrol) (note: the paper spelled this as "salumedrol"--it's assumed this is what they meant) 50 mg IV on days of cytarabine to prevent fever and rash

To be followed by Cytarabine (Cytosar), Idarubicin (Idamycin), Vorinostat (Zolinza) consolidation therapy.

References

1. Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E, Borthakur G, Kadia TM, Konopleva MY, Faderl S, Cortes JE, Brandt M, Hu Y, McCue D, Newsome WM, Pierce SR, de Lima M, Kantarjian HM. Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome. J Clin Oncol. 2012 Jun 20;30(18):2204-10. Epub 2012 May 14. link to original article contains verified 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

1. 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 verified 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

1. 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 verified protocol PubMed
2. 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 verified 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

1. 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 verified 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

1. 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 verified protocol PubMed
2. 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 verified protocol PubMed
3. 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 verified 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

1. 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 verified protocol PubMed
2. 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 verified 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

1. 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 verified protocol PubMed
2. 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 verified 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

1. 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 verified protocol PubMed

Consolidation therapy (AML, acute myeloid leukemia)

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

1. 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 verified protocol PubMed

Cytarabine (Cytosar), Idarubicin (Idamycin), Vorinostat (Zolinza) consolidation

Preceded by Cytarabine (Cytosar), Idarubicin (Idamycin), Vorinostat (Zolinza) induction therapy.

Regimen

• Vorinostat (Zolinza) 500 mg PO TID on days 1-3
• Cytarabine (Cytosar) 750 mg/m2/day IV continuous infusion on days 4-6
• Idarubicin (Idamycin) 8 mg/m2 IV on days 4-5

6-day course x up to 5 cycles

Supportive medications:

• Methylprednisolone (Solu-Medrol) (note: the paper spelled this as "salumedrol"--it's assumed this is what they meant) 50 mg IV on days of cytarabine to prevent fever and rash

To be followed by Vorinostat (Zolinza) maintenance therapy.

References

1. Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E, Borthakur G, Kadia TM, Konopleva MY, Faderl S, Cortes JE, Brandt M, Hu Y, McCue D, Newsome WM, Pierce SR, de Lima M, Kantarjian HM. Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome. J Clin Oncol. 2012 Jun 20;30(18):2204-10. Epub 2012 May 14. link to original article contains verified protocol PubMed

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

1. 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 verified protocol PubMed
2. 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 verified 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

1. 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 verified 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

1. 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 verified protocol PubMed
2. 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 verified 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

1. 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 verified 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

1. 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 verified protocol PubMed
2. 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 verified protocol PubMed
3. 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 verified 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

1. 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 verified protocol PubMed
2. 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

Maintenance therapy (AML, acute myeloid leukemia)

Vorinostat (Zolinza) maintenance

Preceded by Cytarabine (Cytosar), Idarubicin (Idamycin), Vorinostat (Zolinza) consolidation therapy.

Regimen

• Vorinostat (Zolinza) 200 mg PO TID on days 1-14

28-day cycles x up to 12 cycles

References

1. Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E, Borthakur G, Kadia TM, Konopleva MY, Faderl S, Cortes JE, Brandt M, Hu Y, McCue D, Newsome WM, Pierce SR, de Lima M, Kantarjian HM. Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome. J Clin Oncol. 2012 Jun 20;30(18):2204-10. Epub 2012 May 14. link to original article contains verified 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

1. 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

1. 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

1. 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

1. 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 verified protocol PubMed
2. 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 to 5 (administered first)
• Cytarabine (Cytosar) 2000 mg/m2/day IV over 4 hours on days 1 to 5 (administered second, 2 hours after cladribine)
• Mitoxantrone (Novantrone) 10 mg/m2/day IV on days 1 to 3
• Filgrastim (Neupogen) 300 mcg SC on days 0 to 5 (first dose 24 hours before first dose of cladribine)

References

1. 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 content property of HemOnc.org
2. 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

Clofarabine + Cytarabine

Regimen #1, Agura, et al., 2011

• Clofarabine (Clolar) 40 mg/m2/day IV over 1 hour on days 1 to 5
• Cytarabine (Cytosar) 1,000 mg/m2/day IV over 2 hours on days 1 to 5, 4 hours after clofarabine was given

Regimen #2, Faderl, et al., 2012

Number of doses not specified in the paper but, by extrapolation, this is also a 5 day course

• Clofarabine (Clolar) 40 mg/m2/day IV over 1 hour
• Cytarabine (Cytosar) 1,000 mg/m2/day IV over 2 hours, 3 hours after clofarabine was given

References

1. Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J. Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist. 2011;16(2):197-206. doi: 10.1634/theoncologist.2010-0220. Epub 2011 Jan 27. link to original article PubMed
2. Faderl S, Wetzler M, Rizzieri D, Schiller G, Jagasia M, Stuart R, Ganguly S, Avigan D, Craig M, Collins R, Maris M, Kovacsovics T, Goldberg S, Seiter K, Hari P, Greiner J, Vey N, Recher C, Ravandi F, Wang ES, Vasconcelles M, Huebner D, Kantarjian HM. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. doi:10.1200/JCO.2011.37.9743. Epub 2012 May 14. link to original article PubMed

Decitabine (Dacogen)

Regimen

• Decitabine (Dacogen) 20 mg/m2 IV over 1 hour once daily on days 1 to 5

28-day cycles, given until progression of disease or unacceptable toxicity

Supportive medications:

• Hydroxyurea (Hydrea) could be used up until cycle 1 day 15.

References

1. Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20;30(21):2670-7. doi: 10.1200/JCO.2011.38.9429. Epub 2012 Jun 11. link to original article contains verified protocol 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

1. 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

1. 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
2. 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

1. 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 verified 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

1. 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

1. 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
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