Skip to main content
Erschienen in: Current Hematologic Malignancy Reports 2/2014

01.06.2014 | Acute Leukemias (R Stone, Section Editor)

Contemporary Treatment of APL

verfasst von: Elizabeth H. Cull, Jessica K. Altman

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

Acute promyelocytic leukemia (APL) is characterized by coagulopathy, leukopenic presentation and sensitivity to anthracyclines, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). For the last 25 years, APL has been treated with a combination of ATRA and chemotherapy for induction followed by consolidation and maintenance therapy. This general treatment approach has resulted in cure rates of 80–90 %. ATO, originally approved in relapsed APL, has been incorporated into contemporary upfront treatment regimens with excellent response rates. Recent studies show that most patients with APL can be cured with ATRA and ATO alone, eliminating cytotoxic chemotherapy and resulting in superior outcomes compared to standard treatment. We will herein review historical treatment of APL, treatment considerations in specific patient populations, and therapeutic updates.
Literatur
1.
Zurück zum Zitat Douer D. The epidemiology of acute promyelocytic leukemia. Balliere’s Best Pract Clin Hematol. 2003;16:357–67.CrossRef Douer D. The epidemiology of acute promyelocytic leukemia. Balliere’s Best Pract Clin Hematol. 2003;16:357–67.CrossRef
2.
Zurück zum Zitat Estey E, Thall P, Kantarjian H, et al. Association between increased body mass index and a diagnosis of acute promyelocytic leukemia in patients with acute myeloid leukemia. Leukemia. 1997;11:1661–4.PubMedCrossRef Estey E, Thall P, Kantarjian H, et al. Association between increased body mass index and a diagnosis of acute promyelocytic leukemia in patients with acute myeloid leukemia. Leukemia. 1997;11:1661–4.PubMedCrossRef
3.
Zurück zum Zitat Scaglioni PP, Pandolfi PP. The theory of APL revisited. Curr Top Microbiol Immunol. 2007;313:85–100.PubMed Scaglioni PP, Pandolfi PP. The theory of APL revisited. Curr Top Microbiol Immunol. 2007;313:85–100.PubMed
4.
Zurück zum Zitat Huang ME, Ye YC, Chen SR, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72:567–72.PubMed Huang ME, Ye YC, Chen SR, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72:567–72.PubMed
5.
Zurück zum Zitat Castaigne S, Chomienne C, Daniel MT, et al. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990;76:1704–9.PubMed Castaigne S, Chomienne C, Daniel MT, et al. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990;76:1704–9.PubMed
6.
Zurück zum Zitat Warrell Jr RP, Frankel SR, Miller Jr WH, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med. 1991;324:1385–93.PubMedCrossRef Warrell Jr RP, Frankel SR, Miller Jr WH, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med. 1991;324:1385–93.PubMedCrossRef
7.
Zurück zum Zitat Chen ZX, Xue YQ, Zhang R, et al. A clinical and experimental study on all-trans retinoic acid-treated acute promyelocytic leukemia patients. Blood. 1991;78:1413–9.PubMed Chen ZX, Xue YQ, Zhang R, et al. A clinical and experimental study on all-trans retinoic acid-treated acute promyelocytic leukemia patients. Blood. 1991;78:1413–9.PubMed
8.
Zurück zum Zitat Fenaux P, Castaigne S, Dombret H, et al. All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases. Blood. 1992;80:2176–81.PubMed Fenaux P, Castaigne S, Dombret H, et al. All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases. Blood. 1992;80:2176–81.PubMed
9.
Zurück zum Zitat Kanamaru A, Takemoto Y, Tanimoto M, et al. All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group. Blood. 1995;85:1202–6.PubMed Kanamaru A, Takemoto Y, Tanimoto M, et al. All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group. Blood. 1995;85:1202–6.PubMed
10.
Zurück zum Zitat Tallman MS, Andersen JW, Schiffer CA, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337:1021–8.PubMedCrossRef Tallman MS, Andersen JW, Schiffer CA, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337:1021–8.PubMedCrossRef
11.
Zurück zum Zitat Tallman MS, Nabhan C, Feusner JH, Rowe JM. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood. 2002;99:759–67.PubMedCrossRef Tallman MS, Nabhan C, Feusner JH, Rowe JM. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood. 2002;99:759–67.PubMedCrossRef
12.••
Zurück zum Zitat Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369:111–21. Phase III trial that randomized standard risk patients with APL to treatment with ATRA/chemotherapy vs. ATRA/ATO. Results showed non-inferiority of ATRA/ATO regimen compared to ATRA/chemotherapy.PubMedCrossRef Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369:111–21. Phase III trial that randomized standard risk patients with APL to treatment with ATRA/chemotherapy vs. ATRA/ATO. Results showed non-inferiority of ATRA/ATO regimen compared to ATRA/chemotherapy.PubMedCrossRef
13.
Zurück zum Zitat Fenaux P, Chastang C, Chevret S, et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999;94:1192–200.PubMed Fenaux P, Chastang C, Chevret S, et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999;94:1192–200.PubMed
14.
Zurück zum Zitat Mandelli F, Diverio D, Avvisati G, et al. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups. Blood. 1997;90:1014–21.PubMed Mandelli F, Diverio D, Avvisati G, et al. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups. Blood. 1997;90:1014–21.PubMed
15.
Zurück zum Zitat Sanz MA, Martin G, Rayon C, et al. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group. Blood. 1999;94:3015–21.PubMed Sanz MA, Martin G, Rayon C, et al. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group. Blood. 1999;94:3015–21.PubMed
16.
Zurück zum Zitat Fenaux P, Le Deley MC, Castaigne S, et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group. Blood. 1993;82:3241–9.PubMed Fenaux P, Le Deley MC, Castaigne S, et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group. Blood. 1993;82:3241–9.PubMed
17.
Zurück zum Zitat Ades L, Sanz MA, Chevret S, et al. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008;111:1078–84.PubMedCrossRef Ades L, Sanz MA, Chevret S, et al. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008;111:1078–84.PubMedCrossRef
18.
Zurück zum Zitat Sanz MA, Lo Coco F, Martin G, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96:1247–53.PubMed Sanz MA, Lo Coco F, Martin G, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96:1247–53.PubMed
19.
Zurück zum Zitat Sanz MA, Martin G, Gonzalez M, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004;103:1237–43.PubMedCrossRef Sanz MA, Martin G, Gonzalez M, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004;103:1237–43.PubMedCrossRef
20.
Zurück zum Zitat Ades L, Chevret S, Raffoux E, et al. 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;24:5703–10.PubMedCrossRef Ades L, Chevret S, Raffoux E, et al. 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;24:5703–10.PubMedCrossRef
21.
Zurück zum Zitat Nasr R, Guillemin MC, Ferhi O, et al. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation. Nat Med. 2008;14:1333–42.PubMedCrossRef Nasr R, Guillemin MC, Ferhi O, et al. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation. Nat Med. 2008;14:1333–42.PubMedCrossRef
22.
Zurück zum Zitat Niu C, Yan H, Yu T, et al. Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood. 1999;94:3315–24.PubMed Niu C, Yan H, Yu T, et al. Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood. 1999;94:3315–24.PubMed
23.
Zurück zum Zitat Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852–60.PubMed Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852–60.PubMed
24.
Zurück zum Zitat Estey E, Garcia-Manero G, Ferrajoli A, et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006;107:3469–73.PubMedCrossRef Estey E, Garcia-Manero G, Ferrajoli A, et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006;107:3469–73.PubMedCrossRef
25.••
Zurück zum Zitat Iland HJ, Bradstock K, Supple SG, et al. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012;120:1570–80. They used a consolidation regimen of ATO/ATRA, eliminating chemotherapy from the consolidation phase and reported excellent response rates and OS.PubMedCrossRef Iland HJ, Bradstock K, Supple SG, et al. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012;120:1570–80. They used a consolidation regimen of ATO/ATRA, eliminating chemotherapy from the consolidation phase and reported excellent response rates and OS.PubMedCrossRef
26.••
Zurück zum Zitat Powell BL, Moser B, Stock W, et al. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010;116:3751–7. They added ATO to the consolidation phase and reported improved outcomes, particularly in high risk APL patients.PubMedCentralPubMedCrossRef Powell BL, Moser B, Stock W, et al. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010;116:3751–7. They added ATO to the consolidation phase and reported improved outcomes, particularly in high risk APL patients.PubMedCentralPubMedCrossRef
27.
Zurück zum Zitat Ravandi F, Estey E, Jones D, et al. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009;27:504–10.PubMedCrossRef Ravandi F, Estey E, Jones D, et al. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009;27:504–10.PubMedCrossRef
28.
Zurück zum Zitat Shen ZX, Shi ZZ, Fang J, et al. 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;101:5328–35.PubMedCentralPubMedCrossRef Shen ZX, Shi ZZ, Fang J, et al. 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;101:5328–35.PubMedCentralPubMedCrossRef
29.
Zurück zum Zitat Iland HJ CM, Seymour J. The Australasian Leukaemia and lymphoma group APML4 trial - update on APL treatment down under [abstract]. In: 6th International Symposium on Acute Promyelocytic Leukemia Abstract Book 2013 Sept 29-Oct 2; Rome, Italy. Iland HJ CM, Seymour J. The Australasian Leukaemia and lymphoma group APML4 trial - update on APL treatment down under [abstract]. In: 6th International Symposium on Acute Promyelocytic Leukemia Abstract Book 2013 Sept 29-Oct 2; Rome, Italy.
31.
Zurück zum Zitat Sanz MA, Montesinos P, Rayon C, et al. 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;115:5137–46.PubMedCrossRef Sanz MA, Montesinos P, Rayon C, et al. 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;115:5137–46.PubMedCrossRef
32.•
Zurück zum Zitat Coutre S OM, Powell B, et al. A phase III randomized trial (S0521) of maintenance versus observation for patients with previously untreated low/intermediate risk acute promyelocytic leukemia. In: 6th International Symposium on Acute Promyelocytic Leukemia Abstract Book 2013 Sept 29-Oct 2. Phase III randomized trial that compared maintenance therapy to no maintenance therapy in standard risk patients and reported no differences in relapse rates or OS. Coutre S OM, Powell B, et al. A phase III randomized trial (S0521) of maintenance versus observation for patients with previously untreated low/intermediate risk acute promyelocytic leukemia. In: 6th International Symposium on Acute Promyelocytic Leukemia Abstract Book 2013 Sept 29-Oct 2. Phase III randomized trial that compared maintenance therapy to no maintenance therapy in standard risk patients and reported no differences in relapse rates or OS.
33.
Zurück zum Zitat de la Serna J, Montesinos P, Vellenga E, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. 2008;111:3395–402.PubMedCrossRef de la Serna J, Montesinos P, Vellenga E, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. 2008;111:3395–402.PubMedCrossRef
34.
Zurück zum Zitat Micol JB Raffoux E, Boissel N, et al. Do early events excluding patients with acute promyelocytic leukemia (APL) from trial enrollment modify treatment result evaluation? Real-life management of 100 patients referred to the University Hospital Saint-Louis between 2000 and 2010. Blood. 2010;116:473. ASH Annual Meeting Abstracts. Micol JB Raffoux E, Boissel N, et al. Do early events excluding patients with acute promyelocytic leukemia (APL) from trial enrollment modify treatment result evaluation? Real-life management of 100 patients referred to the University Hospital Saint-Louis between 2000 and 2010. Blood. 2010;116:473. ASH Annual Meeting Abstracts.
35.
Zurück zum Zitat Lehmann S, Ravn A, Carlsson L, et al. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia. 2011;25:1128–34.PubMedCrossRef Lehmann S, Ravn A, Carlsson L, et al. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia. 2011;25:1128–34.PubMedCrossRef
36.
Zurück zum Zitat Altman JK, Rademaker A, Cull E, et al. Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death. Leuk Res. 2013;37:1004–9.PubMedCrossRef Altman JK, Rademaker A, Cull E, et al. Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death. Leuk Res. 2013;37:1004–9.PubMedCrossRef
37.
Zurück zum Zitat Rahmé R, Thomas X, Recher C, et al. Early Deaths (ED) in Acute Promyelocytic Leukemia (APL) in France: a retrospective multicenter study in 355 patients (pts). Blood. 2012;120:890. ASH annual Meeting Abstracts. Rahmé R, Thomas X, Recher C, et al. Early Deaths (ED) in Acute Promyelocytic Leukemia (APL) in France: a retrospective multicenter study in 355 patients (pts). Blood. 2012;120:890. ASH annual Meeting Abstracts.
38.
39.
Zurück zum Zitat Tallman MS, Brenner B, Serna Jde L, et al. Meeting report. Acute promyelocytic leukemia-associated coagulopathy, 21 January 2004, London, United Kingdom. Leuk Res. 2005;29:347–51.PubMedCrossRef Tallman MS, Brenner B, Serna Jde L, et al. Meeting report. Acute promyelocytic leukemia-associated coagulopathy, 21 January 2004, London, United Kingdom. Leuk Res. 2005;29:347–51.PubMedCrossRef
40.
Zurück zum Zitat Barbui T, Finazzi G, Falanga A. The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood. 1998;91:3093–102.PubMed Barbui T, Finazzi G, Falanga A. The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood. 1998;91:3093–102.PubMed
41.
Zurück zum Zitat Kelaidi C, Ades L, Fenaux P. Treatment of acute promyelocytic leukemia with high white cell blood counts. Mediterr J Hematol Infect Dis. 2011;3:e2011038.PubMedCentralPubMedCrossRef Kelaidi C, Ades L, Fenaux P. Treatment of acute promyelocytic leukemia with high white cell blood counts. Mediterr J Hematol Infect Dis. 2011;3:e2011038.PubMedCentralPubMedCrossRef
42.
Zurück zum Zitat Frankel SR, Eardley A, Lauwers G, et al. The "retinoic acid syndrome" in acute promyelocytic leukemia. Ann Intern Med. 1992;117:292–6.PubMedCrossRef Frankel SR, Eardley A, Lauwers G, et al. The "retinoic acid syndrome" in acute promyelocytic leukemia. Ann Intern Med. 1992;117:292–6.PubMedCrossRef
43.
Zurück zum Zitat Kelaidi C, Chevret S, De Botton S, et al. Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience. J Clin Oncol. 2009;27:2668–76.PubMedCrossRef Kelaidi C, Chevret S, De Botton S, et al. Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience. J Clin Oncol. 2009;27:2668–76.PubMedCrossRef
44.
Zurück zum Zitat Vahdat L, Maslak P, Miller Jr WH, et al. Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid. Blood. 1994;84:3843–9.PubMed Vahdat L, Maslak P, Miller Jr WH, et al. Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid. Blood. 1994;84:3843–9.PubMed
45.
Zurück zum Zitat de Botton S, Sanz MA, Chevret S, et al. Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Leukemia. 2006;20:35–41.PubMedCrossRef de Botton S, Sanz MA, Chevret S, et al. Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Leukemia. 2006;20:35–41.PubMedCrossRef
46.
Zurück zum Zitat Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113:1875–91.PubMedCrossRef Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113:1875–91.PubMedCrossRef
47.
Zurück zum Zitat Breccia M, Carmosino I, Diverio D, et al. Early detection of meningeal localization in acute promyelocytic leukaemia patients with high presenting leucocyte count. Br J Haematol. 2003;120:266–70.PubMedCrossRef Breccia M, Carmosino I, Diverio D, et al. Early detection of meningeal localization in acute promyelocytic leukaemia patients with high presenting leucocyte count. Br J Haematol. 2003;120:266–70.PubMedCrossRef
48.
Zurück zum Zitat Lengfelder E, Hofmann WK, Nolte F. Management of elderly patients with acute promyelocytic leukemia: progress and problems. Ann Hematol. 2013;92:1181–8.PubMedCentralPubMedCrossRef Lengfelder E, Hofmann WK, Nolte F. Management of elderly patients with acute promyelocytic leukemia: progress and problems. Ann Hematol. 2013;92:1181–8.PubMedCentralPubMedCrossRef
49.
Zurück zum Zitat Park JH, Qiao B, Panageas KS, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011;118:1248–54.PubMedCentralPubMedCrossRef Park JH, Qiao B, Panageas KS, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011;118:1248–54.PubMedCentralPubMedCrossRef
50.
Zurück zum Zitat Ades L, Chevret S, De Botton S, et al. Outcome of acute promyelocytic leukemia treated with all trans retinoic acid and chemotherapy in elderly patients: the European group experience. Leukemia. 2005;19:230–3.PubMedCrossRef Ades L, Chevret S, De Botton S, et al. Outcome of acute promyelocytic leukemia treated with all trans retinoic acid and chemotherapy in elderly patients: the European group experience. Leukemia. 2005;19:230–3.PubMedCrossRef
51.
Zurück zum Zitat Ono T, Takeshita A, Kishimoto Y, et al. Long-term outcome and prognostic factors of elderly patients with acute promyelocytic leukemia. Cancer Sci. 2012;103:1974–8.PubMedCrossRef Ono T, Takeshita A, Kishimoto Y, et al. Long-term outcome and prognostic factors of elderly patients with acute promyelocytic leukemia. Cancer Sci. 2012;103:1974–8.PubMedCrossRef
52.
Zurück zum Zitat Sanz MA, Vellenga E, Rayon C, et al. All-trans retinoic acid and anthracycline monochemotherapy for the treatment of elderly patients with acute promyelocytic leukemia. Blood. 2004;104:3490–3.PubMedCrossRef Sanz MA, Vellenga E, Rayon C, et al. All-trans retinoic acid and anthracycline monochemotherapy for the treatment of elderly patients with acute promyelocytic leukemia. Blood. 2004;104:3490–3.PubMedCrossRef
53.
Zurück zum Zitat Latagliata R, Breccia M, Fazi P, et al. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011;154:564–8.PubMedCrossRef Latagliata R, Breccia M, Fazi P, et al. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011;154:564–8.PubMedCrossRef
54.
Zurück zum Zitat Zhang Y, Zhang Z, Li J, et al. Long-term efficacy and safety of arsenic trioxide for first-line treatment of elderly patients with newly diagnosed acute promyelocytic leukemia. Cancer. 2013;119:115–25.PubMedCrossRef Zhang Y, Zhang Z, Li J, et al. Long-term efficacy and safety of arsenic trioxide for first-line treatment of elderly patients with newly diagnosed acute promyelocytic leukemia. Cancer. 2013;119:115–25.PubMedCrossRef
55.
Zurück zum Zitat Lo-Coco F, Cimino G, Breccia M, et al. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood. 2004;104:1995–9.PubMedCrossRef Lo-Coco F, Cimino G, Breccia M, et al. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood. 2004;104:1995–9.PubMedCrossRef
56.
Zurück zum Zitat Breccia M, Cimino G, Diverio D, et al. Sustained molecular remission after low dose gemtuzumab-ozogamicin in elderly patients with advanced acute promyelocytic leukemia. Haematologica. 2007;92:1273–4.PubMedCrossRef Breccia M, Cimino G, Diverio D, et al. Sustained molecular remission after low dose gemtuzumab-ozogamicin in elderly patients with advanced acute promyelocytic leukemia. Haematologica. 2007;92:1273–4.PubMedCrossRef
57.
Zurück zum Zitat Lo-Coco F, Orlando SM, Platzbecker U. Treatment of acute promyelocytic leukemia. N Engl J Med. 2013;369:1472.PubMedCrossRef Lo-Coco F, Orlando SM, Platzbecker U. Treatment of acute promyelocytic leukemia. N Engl J Med. 2013;369:1472.PubMedCrossRef
58.
Zurück zum Zitat Soignet SL, Maslak P, Wang ZG, et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med. 1998;339:1341–8.PubMedCrossRef Soignet SL, Maslak P, Wang ZG, et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med. 1998;339:1341–8.PubMedCrossRef
59.
Zurück zum Zitat Au WY, Lie AK, Chim CS, et al. Arsenic trioxide in comparison with chemotherapy and bone marrow transplantation for the treatment of relapsed acute promyelocytic leukaemia. Ann Oncol. 2003;14:752–7.PubMedCrossRef Au WY, Lie AK, Chim CS, et al. Arsenic trioxide in comparison with chemotherapy and bone marrow transplantation for the treatment of relapsed acute promyelocytic leukaemia. Ann Oncol. 2003;14:752–7.PubMedCrossRef
60.
Zurück zum Zitat Raffoux E, Rousselot P, Poupon J, et al. Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia. J Clin Oncol. 2003;21:2326–34.PubMedCrossRef Raffoux E, Rousselot P, Poupon J, et al. Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia. J Clin Oncol. 2003;21:2326–34.PubMedCrossRef
61.
Zurück zum Zitat Shigeno K, Naito K, Sahara N, et al. Arsenic trioxide therapy in relapsed or refractory Japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies. Int J Hematol. 2005;82:224–9.PubMedCrossRef Shigeno K, Naito K, Sahara N, et al. Arsenic trioxide therapy in relapsed or refractory Japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies. Int J Hematol. 2005;82:224–9.PubMedCrossRef
62.
Zurück zum Zitat Aribi A, Kantarjian HM, Estey EH, et al. Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia. Cancer. 2007;109:1355–9.PubMedCrossRef Aribi A, Kantarjian HM, Estey EH, et al. Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia. Cancer. 2007;109:1355–9.PubMedCrossRef
63.
Zurück zum Zitat Lu J, Huang X, Bao L, et al. Treatment outcomes in relapsed acute promyelocytic leukemia patients initially treated with all- retinoic acid and arsenic compound-based combined therapies. Oncol Lett. 2014;7:177–82.PubMedCentralPubMed Lu J, Huang X, Bao L, et al. Treatment outcomes in relapsed acute promyelocytic leukemia patients initially treated with all- retinoic acid and arsenic compound-based combined therapies. Oncol Lett. 2014;7:177–82.PubMedCentralPubMed
64.
Zurück zum Zitat Thirugnanam R, George B, Chendamarai E, et al. Comparison of clinical outcomes of patients with relapsed acute promyelocytic leukemia induced with arsenic trioxide and consolidated with either an autologous stem cell transplant or an arsenic trioxide-based regimen. Biol Blood Marrow Transplant. 2009;15:1479–84.PubMedCrossRef Thirugnanam R, George B, Chendamarai E, et al. Comparison of clinical outcomes of patients with relapsed acute promyelocytic leukemia induced with arsenic trioxide and consolidated with either an autologous stem cell transplant or an arsenic trioxide-based regimen. Biol Blood Marrow Transplant. 2009;15:1479–84.PubMedCrossRef
65.
Zurück zum Zitat de Botton S, Fawaz A, Chevret S, et al. Autologous and allogeneic stem-cell transplantation as salvage treatment of acute promyelocytic leukemia initially treated with all-trans-retinoic acid: a retrospective analysis of the European acute promyelocytic leukemia group. J Clin Oncol. 2005;23:120–6.PubMedCrossRef de Botton S, Fawaz A, Chevret S, et al. Autologous and allogeneic stem-cell transplantation as salvage treatment of acute promyelocytic leukemia initially treated with all-trans-retinoic acid: a retrospective analysis of the European acute promyelocytic leukemia group. J Clin Oncol. 2005;23:120–6.PubMedCrossRef
66.
Zurück zum Zitat Pemmaraju N, Tanaka MF, Ravandi F, et al. Outcomes in patients with relapsed or refractory acute promyelocytic leukemia treated with or without autologous or allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk. 2013;13:485–92.PubMedCrossRef Pemmaraju N, Tanaka MF, Ravandi F, et al. Outcomes in patients with relapsed or refractory acute promyelocytic leukemia treated with or without autologous or allogeneic hematopoietic stem cell transplantation. Clin Lymphoma Myeloma Leuk. 2013;13:485–92.PubMedCrossRef
67.••
Zurück zum Zitat Zhu HH, Wu DP, Jin J, et al. Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol. 2013;31:4215–21. This is a randomized controlled trial comparing outcomes with IV arsenic vs. a novel form of oral arsenic. Demonstrated no difference in outcomes with the new formulation.PubMedCrossRef Zhu HH, Wu DP, Jin J, et al. Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol. 2013;31:4215–21. This is a randomized controlled trial comparing outcomes with IV arsenic vs. a novel form of oral arsenic. Demonstrated no difference in outcomes with the new formulation.PubMedCrossRef
68.
Zurück zum Zitat Ozpolat B, Lopez-Berestein G, Adamson P, et al. Pharmacokinetics of intravenously administered liposomal all-trans-retinoic acid (ATRA) and orally administered ATRA in healthy volunteers. J Pharm Pharm Sci. 2003;6:292–301.PubMed Ozpolat B, Lopez-Berestein G, Adamson P, et al. Pharmacokinetics of intravenously administered liposomal all-trans-retinoic acid (ATRA) and orally administered ATRA in healthy volunteers. J Pharm Pharm Sci. 2003;6:292–301.PubMed
69.
Zurück zum Zitat Tsimberidou AM, Tirado-Gomez M, Andreeff M, et al. Single-agent liposomal all-trans retinoic acid can cure some patients with untreated acute promyelocytic leukemia: an update of The University of Texas M. D. Anderson Cancer Center Series. Leuk Lymphoma. 2006;47:1062–8.PubMedCrossRef Tsimberidou AM, Tirado-Gomez M, Andreeff M, et al. Single-agent liposomal all-trans retinoic acid can cure some patients with untreated acute promyelocytic leukemia: an update of The University of Texas M. D. Anderson Cancer Center Series. Leuk Lymphoma. 2006;47:1062–8.PubMedCrossRef
70.
Zurück zum Zitat Jain P, Kantarjian H, Estey E et al. Single-Agent Liposomal All-Trans-Retinoic Acid as Initial Therapy for Acute Promyelocytic Leukemia: 13-Year Follow-Up Data. Clin Lymphoma Myeloma Leuk 2013. Jain P, Kantarjian H, Estey E et al. Single-Agent Liposomal All-Trans-Retinoic Acid as Initial Therapy for Acute Promyelocytic Leukemia: 13-Year Follow-Up Data. Clin Lymphoma Myeloma Leuk 2013.
71.
Zurück zum Zitat Warrell Jr RP. Retinoid resistance in acute promyelocytic leukemia: new mechanisms, strategies, and implications. Blood. 1993;82:1949–53.PubMed Warrell Jr RP. Retinoid resistance in acute promyelocytic leukemia: new mechanisms, strategies, and implications. Blood. 1993;82:1949–53.PubMed
72.
Zurück zum Zitat Shao W, Benedetti L, Lamph WW, et al. A retinoid-resistant acute promyelocytic leukemia subclone expresses a dominant negative PML-RAR alpha mutation. Blood. 1997;89:4282–9.PubMed Shao W, Benedetti L, Lamph WW, et al. A retinoid-resistant acute promyelocytic leukemia subclone expresses a dominant negative PML-RAR alpha mutation. Blood. 1997;89:4282–9.PubMed
73.
Zurück zum Zitat Ohnishi K. PML-RARalpha inhibitors (ATRA, tamibaroten, arsenic troxide) for acute promyelocytic leukemia. Int J Clin Oncol. 2007;12:313–7.PubMedCrossRef Ohnishi K. PML-RARalpha inhibitors (ATRA, tamibaroten, arsenic troxide) for acute promyelocytic leukemia. Int J Clin Oncol. 2007;12:313–7.PubMedCrossRef
74.
Zurück zum Zitat Tobita T, Takeshita A, Kitamura K, et al. Treatment with a new synthetic retinoid, Am80, of acute promyelocytic leukemia relapsed from complete remission induced by all-trans retinoic acid. Blood. 1997;90:967–73.PubMed Tobita T, Takeshita A, Kitamura K, et al. Treatment with a new synthetic retinoid, Am80, of acute promyelocytic leukemia relapsed from complete remission induced by all-trans retinoic acid. Blood. 1997;90:967–73.PubMed
75.
Zurück zum Zitat Naina HV, Levitt D, Vusirikala M, et al. Successful treatment of relapsed and refractory extramedullary acute promyelocytic leukemia with tamibarotene. J Clin Oncol. 2011;29:e534–6.PubMedCrossRef Naina HV, Levitt D, Vusirikala M, et al. Successful treatment of relapsed and refractory extramedullary acute promyelocytic leukemia with tamibarotene. J Clin Oncol. 2011;29:e534–6.PubMedCrossRef
76.
Zurück zum Zitat Di Veroli A, Ramadan SM, Divona M, et al. Molecular remission in advanced acute promyelocytic leukaemia after treatment with the oral synthetic retinoid Tamibarotene. Br J Haematol. 2010;151:99–101.PubMedCrossRef Di Veroli A, Ramadan SM, Divona M, et al. Molecular remission in advanced acute promyelocytic leukaemia after treatment with the oral synthetic retinoid Tamibarotene. Br J Haematol. 2010;151:99–101.PubMedCrossRef
Metadaten
Titel
Contemporary Treatment of APL
verfasst von
Elizabeth H. Cull
Jessica K. Altman
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Current Hematologic Malignancy Reports / Ausgabe 2/2014
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-014-0205-6

Weitere Artikel der Ausgabe 2/2014

Current Hematologic Malignancy Reports 2/2014 Zur Ausgabe

Acute Leukemias (F Ravandi, Section Editor)

Novel Therapeutics in Acute Myeloid Leukemia

ACUTE LEUKEMIAS (R STONE, SECTION EDITOR)

Pediatric-Like Therapy for Adults with ALL

Acute Leukemias (R Stone, Section Editor)

FLT3 Inhibitors in AML: Are We There Yet?

Acute Leukemias (F Ravandi, Section Editor)

Is Targeted Therapy Feasible in Acute Myelogenous Leukemia?

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.