Abstract
The combination of all-trans retinoic acid (ATRA) and idarubicin (AIDA) for induction therapy followed by three cycles of risk-adapted consolidation cycles is considered standard of care for patients with acute promyelocytic leukemia (APL). We report the outcome of 141 patients (median age 51 years; range, 19–82, 31 % ≥60 years) enrolled into the prospective Study Alliance Leukemia (SAL)-AIDA2000 trial, which comprised AIDA-based induction followed by only two courses of risk-adapted consolidation (daunorubicin or mitoxantrone ± cytarabine) followed by 2-year maintenance treatment. The early death rate was 7 % (median age 66 years), and additional 9 % stopped further treatment after induction. The estimated 6-year disease-free survival (DFS) was 80 % in all patients, 84 % in patients ≤60 and 72 % in patients >60 years (p = 0.140). No significant survival differences were observed between the high-risk and the non-high-risk patients (6-year OS 78 vs. 81 %, p = 0.625). Our results confirm the efficacy of a risk-adapted approach in APL patients. Furthermore, long-term outcomes are comparable to the results obtained with three cycles of consolidation. A modification of the number and intensity of conventional consolidation treatment may be a less toxic but equally effective approach and should be considered for further evaluation in randomized clinical trials in APL.
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References
Larson RA, Kondo K, Vardiman JW, Butler AE, Golomb HM, Rowley JD (1984) Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. Am J Med 76:827–841
Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P, Degos L (1990) All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood 76:1704–1709
Warrell RP Jr, Frankel SR, Miller WH Jr, Scheinberg DA, Itri LM, Hittelman WN, Vyas R, Andreeff M, Tafuri A, Jakubowski A (1991) Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 324:1385–1393
Chen ZX, Xue YQ, Zhang R, Tao RF, Xia XM, Li C, Wang W, Zu WY, Yao XZ, Ling BJ (1991) A clinical and experimental study on all-trans retinoic acid-treated acute promyelocytic leukemia patients. Blood 78:1413–1419
Degos L, Chomienne C, Daniel MT, Berger R, Dombret H, Fenaux P, Castaigne S (1990) Treatment of first relapse in acute promyelocytic leukemia with all-trans retinoic acid. Lancet 336:1440–1441
Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell RP Jr (1992) The “retinoic acid syndrome” in acute promyelocytic leukemia. Ann Intern Med 117:292–296
Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH (1997) All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 337:1021–1028
Fenaux P, Wattel E, Archimbaud E, Sanz M, Hecquet B, Fegueux N, Guerci A, Link H, Fey M, Castaigne S (1994) Prolonged follow-up confirms that all-trans retinoic acid followed by chemotherapy reduces the risk of relapse in newly diagnosed acute promyelocytic leukemia. The French APL Group. Blood 84:666–667
Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, Broccia G, Cerri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo CF (1997) 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 90:1014–1021
Sanz MA, Martin G, Rayon C, Esteve J, Gonzalez M, Diaz-Mediavilla J, Bolufer P, Barragan E, Terol MJ, Gonzalez JD, Colomer D, Chillon C, Rivas C, Gomez T, Ribera JM, Bornstein R, Roman J, Calasanz MJ, Arias J, Alvarez C, Ramos F, Deben G (1999) 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 94:3015–3021
Sanz MA, Grimwade D, Tallman MS, Lowenberg B, Fenaux P, Estey EH, Naoe T, Lengfelder E, Buchner T, Dohner H, Burnett AK, Lo-Coco F (2009) Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 113:1875–1891
Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD (2003) Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 21:4642–4649
Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U, Wermke M, Bornhauser M, Ritter M, Neubauer A, Ehninger G, Illmer T (2002) Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 99:4326–4335
Thiede C, Koch S, Creutzig E, Steudel C, Illmer T, Schaich M, Ehninger G (2006) Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 107:4011–4020
Sanz MA, Lo Coco F, Martin G, Avvisati G, Rayon C, Barbui T, Diaz-Mediavilla J, Fioritoni G, Gonzalez JD, Liso V, Esteve J, Ferrara F, Bolufer P, Bernasconi C, Gonzalez M, Rodeghiero F, Colomer D, Petti MC, Ribera JM, Mandelli F (2000) 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 96:1247–1253
Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F (2010) Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood 116:3171–3179
Juliusson G, Lazarevic V, Horstedt AS, Hagberg O, Hoglund M (2012) Acute myeloid leukemia in the real world: why population-based registries are needed. Blood 119:3890–3899
Lengfelder E, Haferlach C, Saussele S, Haferlach T, Schultheis B, Schnittger S, Ludwig WD, Staib P, Aul C, Gruneisen A, Kern W, Reichle A, Serve H, Berdel WE, Braess J, Spiekermann K, Wormann B, Sauerland MC, Heinecke A, Hiddemann W, Hehlmann R, Buchner T (2009) High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG. Leukemia 23:2248–2258
Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Loffler H, Staib P, Heyll A, Seifarth W, Saussele S, Fonatsch C, Gassmann W, Ludwig WD, Hochhaus A, Beelen D, Aul C, Sauerland MC, Heinecke A, Hehlmann R, Wormann B, Hiddemann W, Buchner T (2000) Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group. Leukemia 14:1362–1370
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 (2011) GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukemia. Long-term results and prognostic factors. Br J Haematol 154:564–568
Lo CF, Diverio D, Avvisati G, Petti MC, Meloni G, Pogliani EM, Biondi A, Rossi G, Carlo-Stella C, Selleri C, Martino B, Specchia G, Mandelli F (1999) Therapy of molecular relapse in acute promyelocytic leukemia. Blood 94:2225–2229
Lengfelder E, Hofmann WK, Nowak D (2012) Impact of arsenic trioxide in the treatment of acute promyelocytic leukemia. Leukemia 26:433–442
Acknowledgments
We thank S. Helas for assistance in formatting the figures. UP is supported by a grant within the SFB 655 from the Deutsche Forschungsgemeinschaft (DFG).
Authors’ contributions
UP, US, GE, MS and CR designed the study, collected, analyzed and interpreted data, and wrote the manuscript. MK collected, analyzed and interpreted data and edited the manuscript. All other authors interpreted data and edited the paper. Presented in part as an abstract at the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA, USA, December 12, 2011.
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The authors declare that they have no conflict of interest.
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Röllig, C., Schäfer-Eckardt, K., Hänel, M. et al. Two cycles of risk-adapted consolidation therapy in patients with acute promyelocytic leukemia. Results from the SAL-AIDA2000 trial. Ann Hematol 94, 557–563 (2015). https://doi.org/10.1007/s00277-014-2242-6
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DOI: https://doi.org/10.1007/s00277-014-2242-6