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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
Authors: Lucena-Araujo, Antonio R.
Kim, Haesook T.
Jacomo, Rafael H.
Melo, Raul A.
Bittencourt, Rosane
Pasquini, Ricardo
Pagnano, Katia
Fagundes, Evandro M.
Chauffaille, Maria de Lourdes [UNIFESP]
Chiattone, Carlos S.
Lima, Ana Silvia
Ruiz-Argueelles, Guillermo
Soledad Undurraga, Maria
Martinez, Lem
Kwaan, Hau C.
Gallagher, Robert
Niemeyer, Charlotte M.
Schrier, Stanley L.
Tallman, Martin S.
Grimwade, David
Ganser, Arnold
Berliner, Nancy
Ribeiro, Raul C.
Lo-Coco, Francesco
Lowenberg, Bob
Sanz, Miguel A.
Rego, Eduardo M.
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
Keywords: Acute promyelocytic leukemia
FLT3-ITD mutations
Developing countries
Issue Date: 1-Dec-2014
Publisher: Springer
Citation: Annals of Hematology. New York: Springer, v. 93, n. 12, p. 2001-2010, 2014.
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.
ISSN: 0939-5555
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