Acute promyelocytic leukemia
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Induction therapy
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 verified 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 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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 verified 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 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
Maintenance therapy
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 verified 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 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
- 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
- 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
- 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
- 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
- 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
- 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