Acute myeloid leukemia
Induction therapy (APL, acute promyelocytic leukemia)
ATRA, Daunorubicin, Cytarabine #1
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- Daunorubicin (Cerubidine) 60 mg/m2 IV days 1-3
- Cytarabine (Cytosar) 200 mg/m2 IV days 1-7
7-day initial induction chemotherapy, with ongoing use of ATRA
To be followed by Daunorubicin, Cytarabine, IT chemo consolidation therapy.
References
ATRA, Daunorubicin, Cytarabine #2
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- Daunorubicin (Cerubidine) 50 mg/m2 IV days 1-4
- Cytarabine (Cytosar) 200 mg/m2 IV days 1-7
7-day initial induction chemotherapy, with ongoing use of ATRA
To be followed by Arsenic, ATRA, Daunorubicin consolidation therapy.
References
AIDA
AIDA: ATRA, IDArubicin
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- For patients <20 years old, All-trans retinoic acid (ATRA) dose was 25 mg/m2/day, divided into two equal doses PO BID
- Idarubicin (Idamycin) 12 mg/m2 IV days 2, 4, 6, 8
8-day initial induction chemotherapy, with ongoing use of ATRA
To be followed by AIDA consolidation therapy or ATRA, idarubicin, cytarabine, mitoxantrone consolidation therapy.
References
- Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to full article contains protocol PubMed
- Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains protocol PubMed
ATRA & arsenic
Regimen
Estey 2006:
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 1 hour daily, starting day 11 and continuing until remission
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)
Consolidation therapy (APL, acute promyelocytic leukemia)
Daunorubicin, Cytarabine, IT chemo
Regimen
- Daunorubicin (Cerubidine) 60 mg/m2 IV on days 1-3
- Cytarabine (Cytosar) 200 mg/m2 IV on days 1-7
7 days of therapy, THEN
- Daunorubicin (Cerubidine) 45 mg/m2 IV on days 1-3
- Cytarabine (Cytosar) 1500-2000 mg/m2 IV every 12 hours on days 1-7
- 5 doses of intrathecal chemotherapy
7 days of therapy
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
Arsenic, ATRA, Daunorubicin
Regimen
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV days 1-5, 8-12, 15-19, 22-26, 29-33
5-week cycles x 2 cycles, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting days 1-7
- Daunorubicin (Cerubidine) 50 mg/m2 IV days 1-3
7-day cycles x 2 cycles
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
AIDA - consolidation therapy
AIDA: ATRA, IDArubicin
Regimen
- Idarubicin (Idamycin) 5 mg/m2 IV days 1-4 (administered second, 3 hours after cytarabine infusion complete)
- Cytarabine (Cytosar) 1000 mg/m2 IV over 6 hours on days 1-4 (administered first)
4-day course of therapy, THEN
- Mitoxantrone (Novantrone) 10 mg/m2 IV days 1-5 (administered first)
- Etoposide (Vepesid) 100 mg/m2 IV over 45-60 minutes (administered second, 12 hours after start of mitoxantrone) days 1-5
5-day course of therapy, THEN
- Idarubicin (Idamycin) 12 mg/m2 IV day 1
- Cytarabine (Cytosar) 150 mg/m2 IV every 8 hours (450 mg/m2/day total dosage) days 1-5
- Thioguanine (Tabloid) 70 mg/m2 PO every 8 hours (210 mg/m2/day total dosage) days 1-5
5-day course of therapy
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
- Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA (Gruppo Italiano Malattie Ematologische dell'Adulto) Italian Cooperative Group. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. link to original article contains protocol PubMed
- Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to full article contains protocol PubMed
- Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains protocol PubMed
ATRA, idarubicin, cytarabine, mitoxantrone
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
- Idarubicin (Idamycin) 5-7 mg/m2 IV days 1-4 -- 5 mg/m2 dosage used for low risk patients, 7 mg/m2 dosage used for intermediate risk patients
- Cytarabine (Cytosar) 1000 mg/m2 IV days 1-4
15-day cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
- Mitoxantrone (Novantrone) 10 mg/m2 IV days 1-5
15-day cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
- Idarubicin (Idamycin) 12 mg/m2 IV day 1
- Cytarabine (Cytosar) 450 mg/m2, divided into three equal doses IV every 8 hours, days 1-4
15-day cycle
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
ATRA & arsenic - consolidation
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, 7 days per week on weeks 1-2, 5-6, 9-10, 13-14, 17-18, 21-22, 25-26
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 1 hour daily, 5 consecutive days per week on weeks 1-4, 9-12, 17-20, 25-28
28 weeks of therapy
To be followed by ATRA or Mercaptopurine, Methotrexate, alternating with ATRA maintenance therapy.
References
- Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006 May 1;107(9):3469-73. Epub 2005 Dec 22. link to original article contains protocol PubMed
Consolidation therapy (AML, acute myeloid leukemia)
Maintenance therapy (APL, acute promyelocytic leukemia)
ATRA
AIDA: ATRA, IDArubicin
Regimen
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
3-month cycles x 2 years (8 total cycles)
References
- Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA (Gruppo Italiano Malattie Ematologische dell'Adulto) Italian Cooperative Group. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. link to original article contains protocol PubMed
- Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to full article contains protocol PubMed
- Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains protocol PubMed
Mercaptopurine, Methotrexate, alternating with ATRA
AIDA: ATRA, IDArubicin
Regimen
Part A:
- Mercaptopurine (Purinethol) 1 mg/kg PO daily
- Methotrexate (MTX) 15 mg/m2 OR 0.25 mg/kg IM weekly -- papers below list different dosages
90-day course of therapy, THEN
Part B:
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
15-day course of therapy. Alternate between Part A and Part B for a total of 2 years
References
- Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA (Gruppo Italiano Malattie Ematologische dell'Adulto) Italian Cooperative Group. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. link to original article contains protocol PubMed
- Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains protocol PubMed