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

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 Lucena-Araujo, Antonio R. Google Scholar
Kim, Haesook T. Google Scholar
Jacomo, Rafael H. Google Scholar
Melo, Raul A. Google Scholar
Bittencourt, Rosane Google Scholar
Pasquini, Ricardo Google Scholar
Pagnano, Katia Google Scholar
Fagundes, Evandro M. Google Scholar
Chauffaille, Maria de Lourdes Autor UNIFESP Google Scholar
Chiattone, Carlos S. Google Scholar
Lima, Ana Silvia Google Scholar
Ruiz-Argueelles, Guillermo Google Scholar
Soledad Undurraga, Maria Google Scholar
Martinez, Lem Google Scholar
Kwaan, Hau C. Google Scholar
Gallagher, Robert Google Scholar
Niemeyer, Charlotte M. Google Scholar
Schrier, Stanley L. Google Scholar
Tallman, Martin S. Google Scholar
Grimwade, David Google Scholar
Ganser, Arnold Google Scholar
Berliner, Nancy Google Scholar
Ribeiro, Raul C. Google Scholar
Lo-Coco, Francesco Google Scholar
Lowenberg, Bob Google Scholar
Sanz, Miguel A. Google Scholar
Rego, Eduardo M. Google Scholar
Institution Universidade de São Paulo (USP)
Ctr Cell Based Therapy
Dana Farber Canc Inst
Fundacao HEMOPE
Univ Fed Rio Grande do Sul
Univ Fed Parana
Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de São Paulo (UNIFESP)
Santa Casa Med Sch
Clin Ruiz Puebla
Hosp Salvador
Asociac Espanola Primera Socorros Mutuos
Northwestern Univ
Albert Einstein Canc Ctr
Univ Med Ctr
Stanford Univ
Weill Cornell Med Coll
Kings Coll London
Hannover Med Sch
Harvard Univ
St Jude Childrens Res Hosp
Univ Roma Tor Vergata
Santa Lucia Fdn
Erasmus Univ
Univ Valencia
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.
Keywords Acute promyelocytic leukemia
IC-APL
FLT3-ITD mutations
Developing countries
ATRA
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 1998/14247-6
CNPq: 573754/2008-0
FAPESP: 2007/55067-1
Date 2014-12-01
Published in Annals of Hematology. New York: Springer, v. 93, n. 12, p. 2001-2010, 2014.
ISSN 0939-5555 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 2001-2010
Origin http://dx.doi.org/10.1007/s00277-014-2142-9
Access rights Closed access
Type Article
Web of Science ID WOS:000344803100006
URI http://repositorio.unifesp.br/handle/11600/38492

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