Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukemia study

Abstract

Activating internal tandem duplication (ITD) mutations in the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor outcome in acute myeloid leukemia, but their prognostic impact in acute promyelocytic leukemia (APL) remains controversial. Here, we screened for FLT3-ITD mutations in 171 APL patients, treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. We identified FLT3-ITD mutations in 35 patients (20 %). FLT3-ITD mutations were associated with higher white blood cell counts (P < 0.0001), relapse-risk score (P = 0.0007), higher hemoglobin levels (P = 0.0004), higher frequency of the microgranular morphology (M3v) subtype (P = 0.03), and the short PML/RARA (BCR3) isoform (P < 0.0001). After a median follow-up of 38 months, FLT3-ITDpositive patients had a lower 3-year overall survival rate (62 %) compared with FLT3-ITDnegative patients (82 %) (P = 0.006). The prognostic impact of FLT3-ITD on survival was retained in multivariable analysis (hazard ratio: 2.39, 95 % confidence interval [CI] 1.17–4.89; P = 0.017). Nevertheless, complete remission (P = 0.07), disease-free survival (P = 0.24), and the cumulative incidence of relapse (P = 0.94) rates were not significantly different between groups. We can conclude that FLT3-ITD mutations are associated with several hematologic features in APL, in particular with high white blood cell counts. In addition, FLT3-ITD may independently predict a shorter survival in patients with APL treated with ATRA and anthracycline-based chemotherapy.

DOI: 10.1007/s00277-014-2142-9

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@article{LucenaAraujo2014InternalTD, title={Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukemia study}, author={Antonio R Lucena-Araujo and Haesook T Kim and Rafael Henriques J{\'a}como and Raul Antonio M. Melo and Rosane Isabel Bittencourt and Ricardo Pasquini and K{\'a}tia B{\'o}rgia Barbosa Pagnano and Evandro Maranh{\~a}o Fagundes and Maria de Lourdes Lopes Ferrari Chauffaille and Carlos S{\'e}rgio Chiattone and Ana S{\'i}lvia Gouveia Lima and Guillermo J Ruiz-Arg{\"{u}elles and Mar{\'i}a Soledad Undurraga and Lem Mart{\'i}nez and Hau C . Kwaan and Robert E. Gallagher and Charlotte Marie Niemeyer and Stanley L. Schrier and Martin S. Tallman and David J Grimwade and Arnold Ganser and Nancy Berliner and Raul C. Ribeiro and Francesco Lo-Coco and Bob L{\"{o}wenberg and Miguel {\'A}ngel Sanz and Eduardo M Rego}, journal={Annals of Hematology}, year={2014}, volume={93}, pages={2001-2010} }