Difference between revisions of "Acute promyelocytic leukemia"
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To be followed by [[#ATRA_.26_arsenic_-_consolidation|ATRA & arsenic]] consolidation therapy. | To be followed by [[#ATRA_.26_arsenic_-_consolidation|ATRA & arsenic]] consolidation therapy. | ||
− | ===Regimen #2, Estey, et al. 2006=== | + | ===Regimen #2, Estey, et al. 2006 and Ravandi, et al. 2009=== |
Level of Evidence: | Level of Evidence: | ||
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− | style="background:# | + | style="background:#EEEE00; |
padding:3px 6px 3px 6px; | padding:3px 6px 3px 6px; | ||
border-color:black; | border-color:black; | ||
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− | border-style:solid;">Phase | + | border-style:solid;">Phase II</span> |
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+ | ''There are two variations of this regimen as published. The earlier publication covers a part of the whole cohort and includes only the initial protocol where arsenic trioxide was started on day 10. Additionally in the initial protocol gemtuzumab ozogamicin was only used for high risk patients. After a death due to hyperleukocytosis and intracranial hemorrhage the protocol was modified so arsenic trioxide was started on day 1 as published in Ravandi, et al. 2009. and gemtuzumab ozogamicin was given if WBC count went >30 X 10<sup>9</sup>/L for any patient in the first four weeks of therapy.'' | ||
*[[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. | *[[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 once per day, starting day 11 and continuing until remission | + | *[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 1 hour once per day, starting day 11 and continuing until remission or starting day 1 and continuing until remission |
+ | |||
+ | ''and for High Risk Patients (Initial WBC ≥ 10 X 10<sup>9</sup>/L)'' | ||
+ | |||
+ | *[[Gemtuzumab ozogamicin (Mylotarg)]] 9 mg/m2 IV once on day 1 | ||
+ | |||
To be followed by [[#ATRA_.26_arsenic_-_consolidation|ATRA & arsenic]] consolidation therapy. | To be followed by [[#ATRA_.26_arsenic_-_consolidation|ATRA & arsenic]] consolidation therapy. | ||
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# 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 verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15044693 PubMed] | # 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 verified 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 verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16373661 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 verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16373661 PubMed] | ||
+ | #Ravandi F, Estey E, Jones D, Faderl S, O'Brien S, Fiorentino J, Pierce S, Blamble D, Estrov Z, Wierda W, Ferrajoli A, Verstovsek S, Garcia-Manero G, Cortes J, Kantarjian H. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009 Feb 1;27(4):504-10. doi: 10.1200/JCO.2008.18.6130. Epub 2008 Dec 15. [http://jco.ascopubs.org/content/27/4/504.abstract?sid=391321bf-2b10-480f-85fe-416f57140273] '''contains link to verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19075265 PubMed] | ||
# Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874. [http://www.nejm.org/doi/full/10.1056/NEJMoa1300874 link to original article] '''contains link to verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23841729 PubMed] | # Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874. [http://www.nejm.org/doi/full/10.1056/NEJMoa1300874 link to original article] '''contains link to verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23841729 PubMed] | ||
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=Consolidation therapy= | =Consolidation therapy= |
Revision as of 21:49, 7 September 2013
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Induction therapy
APL 2000 (EAPLG) induction
Regimen
Level of Evidence: Phase III
- 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 to 5
- Cytarabine (Cytosar) 200 mg/m2 IV on days 3 to 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 to 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
APML4 induction
Regimen, Iland, et al. 2012 (APML4)
Level of Evidence: Phase II
- Idarubicin (Idamycin) 12 mg/m2 IV once per day on days 2, 4, 6, 8
- Patients 61 to 70 years old received: Idarubicin (Idamycin) 9 mg/m2 IV once per day on days 2, 4, 6, 8
- Patients >70 years old received: Idarubicin (Idamycin) 6 mg/m2 IV once per day on days 2, 4, 6, 8
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1 to 36
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 2 hours once per day on days 9 to 36
36-day course; after 3 to 4 weeks, proceed to consolidation cycle 1
Supportive medications:
- Prednisone (Sterapred) 1 mg/kg PO once per day on days 1 to 10, or until WBC falls below 1 x 109/L (1,000/uL), or until resolution of differentiation syndrome (whichever occurs last)
- Hemostatic support : Values checked and products transfused once or twice per day to keep platelet count > 30 x 109/L (30,000/uL), fibrinogen >1.5 g/L (150 mg/dL), normal PT and PTT
- Electrolyte support while on Arsenic trioxide (Trisenox): supplemental potassium and magnesium given to keep levels in the upper half of their normal ranges
To be followed by APML4 consolidation therapy
References
- Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R,Seldon M, Taper J, Szer J, Moore J, Bashford J, Seymour JF; Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012 Aug 23;120(8):1570-80. Epub 2012 Jun 19. link to original article contains verified protocol PubMed
North American Leukemia Intergroup Study C9710 induction
Regimen
Level of Evidence: Phase III
- 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 to 6
- Cytarabine (Cytosar) 200 mg/m2/day IV continuous infusion on days 3 to 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
Level of Evidence: Phase III
- 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 once on days 2, 4, 6, 8
8-day initial induction chemotherapy, with ongoing use of ATRA
To be followed by AIDA 0493 consolidation therapy.
References
- Avvisati G, Lo Coco F, Diverio D, Falda M, Ferrara F, Lazzarino M, Russo D, Petti MC, Mandelli F. AIDA (all-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) pilot study. Blood. 1996 Aug 15;88(4):1390-8. link to full 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
- Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler
W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874. link to original article contains link to 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
Level of Evidence: Phase III
- Arsenic trioxide (Trisenox) 10 mg (0.15 mg/kg for pediatric patients) IV over 2 to 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 to 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 to 3 hours daily x "10 days a month"
1-month cycles x 6 months
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
- 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 #1, Lo-Coco, et al. 2013
Level of Evidence: Phase III
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until hematologic complete remission or maximum of 60 days.
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 2 hours once per day, starting day 1 and continuing until hematologic complete remission or maximum of 60 days.
To be followed by ATRA & arsenic consolidation therapy.
Regimen #2, Estey, et al. 2006 and Ravandi, et al. 2009
Level of Evidence: Phase II
There are two variations of this regimen as published. The earlier publication covers a part of the whole cohort and includes only the initial protocol where arsenic trioxide was started on day 10. Additionally in the initial protocol gemtuzumab ozogamicin was only used for high risk patients. After a death due to hyperleukocytosis and intracranial hemorrhage the protocol was modified so arsenic trioxide was started on day 1 as published in Ravandi, et al. 2009. and gemtuzumab ozogamicin was given if WBC count went >30 X 109/L for any patient in the first four weeks of therapy.
- 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 once per day, starting day 11 and continuing until remission or starting day 1 and continuing until remission
and for High Risk Patients (Initial WBC ≥ 10 X 109/L)
- Gemtuzumab ozogamicin (Mylotarg) 9 mg/m2 IV once on day 1
To be followed by ATRA & arsenic consolidation therapy.
Regimen #3, Shen, et al. 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
- Ravandi F, Estey E, Jones D, Faderl S, O'Brien S, Fiorentino J, Pierce S, Blamble D, Estrov Z, Wierda W, Ferrajoli A, Verstovsek S, Garcia-Manero G, Cortes J, Kantarjian H. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009 Feb 1;27(4):504-10. doi: 10.1200/JCO.2008.18.6130. Epub 2008 Dec 15. [1] contains link to verified protocol PubMed
- Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874. link to original article contains link to verified protocol PubMed
Consolidation therapy
APL 2000 (EAPLG) consolidation
Preceded by APL 2000 (EAPLG) induction therapy.
Regimen
Level of Evidence: Phase III
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 to 3
- Cytarabine (Cytosar) 200 mg/m2 IV on days 1 to 7
Followed by:
- Daunorubicin (Cerubidine) 45 mg/m2 IV on days 1 to 3
- Cytarabine (Cytosar) 1000 mg/m2 IV every 12 hours on days 1 to 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 to 3
- Cytarabine (Cytosar) 200 mg/m2 IV on days 1 to 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 to 3
- If age <50 years old: Cytarabine (Cytosar) 2000 mg/m2 IV every 12 hours on days 1 to 5 (10 total doses)
- If age 50-60 years old: Cytarabine (Cytosar) 1500 mg/m2 IV every 12 hours on days 1 to 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 to 3
Followed by:
- Daunorubicin (Cerubidine) 45 mg/m2 IV on days 1 to 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
APML4 consolidation
Preceded by APML4 induction therapy.
Regimen, Iland, et al. 2012 (APML4)
Level of Evidence: Phase II
Consolidation cycle 1
Given 3 to 4 weeks after completion of induction.
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1 to 28
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV once per day on days 1 to 28
4-week course; after 3 to 4 weeks, proceed to consolidation cycle 2
Consolidation cycle 2
Given 3 to 4 weeks after completion of consolidation cycle 1.
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1 to 7, 15 to 21, 29 to 35
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
5-week course; after 3 to 4 weeks, proceed to APML4 maintenance
References
- Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R,Seldon M, Taper J, Szer J, Moore J, Bashford J, Seymour JF; Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012 Aug 23;120(8):1570-80. Epub 2012 Jun 19. 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
Level of Evidence: Phase III
Consolidation therapy starts within 2 to 4 weeks of hematologic remission:
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV once daily on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 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 to 7
- Daunorubicin (Cerubidine) 50 mg/m2 IV once daily on days 1 to 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
Level of Evidence: Phase III
As detailed in Avvisati, et al., 2002:
- Idarubicin (Idamycin) 5 mg/m2 IV once daily on days 1 to 4 (administered second, 3 hours after cytarabine infusion complete)
- Cytarabine (Cytosar) 1000 mg/m2 IV over 6 hours on days 1 to 4 (administered first)
4-day course of therapy, THEN
- Mitoxantrone (Novantrone) 10 mg/m2 IV once daily on days 1 to 5 (administered first)
- Etoposide (Vepesid) 100 mg/m2 IV over 45 to 60 minutes (administered second, 12 hours after start of mitoxantrone) days 1 to 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 to 5
- Thioguanine (Tabloid) 70 mg/m2 PO every 8 hours (210 mg/m2/day total dosage) days 1 to 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 to 15
- Idarubicin (Idamycin) 7 mg/m2 IV once daily on days 1 to 4
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Mitoxantrone (Novantrone) 10 mg/m2 IV once daily on days 1 to 5
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Idarubicin (Idamycin) 12 mg/m2 IV once on 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 to 15
- Idarubicin (Idamycin) 7 mg/m2 IV once daily on days 1 to 4
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Mitoxantrone (Novantrone) 10 mg/m2 IV once daily on days 1 to 5
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Idarubicin (Idamycin) 12 mg/m2 IV once on days 1 & 2
1-month cycle
Low risk:
- Idarubicin (Idamycin) 5 mg/m2 IV once daily on days 1 to 4
1-month cycle, THEN
- Mitoxantrone (Novantrone) 10 mg/m2 IV once daily on days 1 to 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 to 15
- Idarubicin (Idamycin) 5 mg/m2 IV once daily on days 1 to 4
- Cytarabine (Cytosar) 1000 mg/m2 IV once daily on days 1 to 4
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Mitoxantrone (Novantrone) 10 mg/m2 IV once daily on days 1 to 5
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 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 to 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 to 15
- Idarubicin (Idamycin) 7 mg/m2 IV once daily on days 1 to 4
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Mitoxantrone (Novantrone) 10 mg/m2 IV once daily on days 1 to 3
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Idarubicin (Idamycin) 12 mg/m2 IV once on 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 to 15
- Idarubicin (Idamycin) 5 mg/m2 IV once daily on days 1 to 4
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Mitoxantrone (Novantrone) 10 mg/m2 IV once daily on days 1 to 3
1-month cycle, THEN
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
- Idarubicin (Idamycin) 12 mg/m2 IV once on 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
Level of Evidence: Phase II
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, 7 days per week on weeks 1 to 2, 5 to 6, 9 to 10, 13 to 14, 17 to 18, 21 to 22, 25 to 26
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 1 hour daily, 5 consecutive days per week on weeks 1 to 4, 9 to 12, 17 to 20, 25 to 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
Level of Evidence: Phase III
- 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 to 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
APML4 maintenance
Preceded by APML4 consolidation therapy.
Regimen, Iland, et al. 2012 (APML4)
Level of Evidence: Phase II
Given 3 to 4 weeks after completion of consolidation cycle 2.
- All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID on days 1 to 14
- Methotrexate (MTX) 5 to 15 mg/m2/week PO on days 15 to 90
- Mercaptopurine (Purinethol) 50 to 90 mg/m2 PO once per day on days 15 to 90
- Methotrexate (MTX) and Mercaptopurine (Purinethol) doses titrated to ANC 1 to 2 x 109/L (1,000 to 2,000/uL) and minimizing hepatotoxicity
90-day cycles x 8 cycles
References
- Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R,Seldon M, Taper J, Szer J, Moore J, Bashford J, Seymour JF; Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012 Aug 23;120(8):1570-80. Epub 2012 Jun 19. 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 to 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
Level of Evidence: Phase III
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 to 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 to 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
Relapsed/refractory
Arsenic-based re-induction followed by consolidation and autologous stem cell transplant
Regimen
Level of Evidence: Phase II
Induction
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 2 hours once daily days 1 to [*]
- Idarubicin (Idamycin) 12 mg/m2 IV once over 30 minutes on days 1 & 2 [**]
- Intrathecal therapy given once after platelet recovery, consisting of Methotrexate (MTX) 15 mg IT, Cytarabine (Cytosar) 40 mg IT, and corticosteroids (Prednisolone (Millipred) 10 mg IT or Dexamethasone (Decadron) 4 mg IT
Special notes: [*] Arsenic was continued until complete remission or maximum of 60 days [**] Idarubicin was added under special conditions, see text for details
Consolidation #1 and #2
- Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 2 hours once daily days 1 to [*]
- Intrathecal therapy given once after platelet recovery, consisting of Methotrexate (MTX) 15 mg IT, Cytarabine (Cytosar) 40 mg IT, and corticosteroids (Prednisolone (Millipred) 10 mg IT or Dexamethasone (Decadron) 4 mg IT
Consolidation #3
- Cytarabine (Cytosar) 2 g/m2 IV over 3 hours twice daily on days 1 to 4 (8 doses, total)
- Filgrastim (Neupogen) starting on day 6 (dose, frequency not specified)
Peripheral blood stem cells collected upon WBC recovery, followed by:
- Busulfan/melphalan autologous stem cell transplant, see Transplant conditioning regimens
References
- Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. doi: 10.1182/blood-2012-11-466862. Epub 2013 Feb 14. link to original article Contains verified protocol PubMed