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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Lucena-Araujo, Antonio R. [1, 2] ; Kim, Haesook T. [3] ; Jacomo, Rafael H. [1, 2] ; Melo, Raul A. [4] ; Bittencourt, Rosane [5] ; Pasquini, Ricardo [6] ; Pagnano, Katia [7] ; Fagundes, Evandro M. [8] ; Chauffaille, Maria de Lourdes [9] ; Chiattone, Carlos S. [10] ; Lima, Ana Silvia [1, 2] ; Ruiz-Argueelles, Guillermo [11] ; Soledad Undurraga, Maria [12] ; Martinez, Lem [13] ; Kwaan, Hau C. [14] ; Gallagher, Robert [15] ; Niemeyer, Charlotte M. [16] ; Schrier, Stanley L. [17] ; Tallman, Martin S. [18] ; Grimwade, David [19] ; Ganser, Arnold [20] ; Berliner, Nancy [21] ; Ribeiro, Raul C. [22] ; Lo-Coco, Francesco [23, 24] ; Lowenberg, Bob [25] ; Sanz, Miguel A. [26] ; Rego, Eduardo M. [27, 1, 2]
Total Authors: 27
Affiliation:
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[1] Med Sch Ribeirao Preto, Ribeirao Preto - Brazil
[2] Ctr Cell Based Therapy, Ribeirao Preto - Brazil
[3] Dana Farber Canc Inst, Boston, MA 02115 - USA
[4] Fundacao HEMOPE, Recife, PE - Brazil
[5] Univ Fed Rio Grande do Sul, Porto Alegre, RS - Brazil
[6] Univ Fed Parana, BR-80060000 Curitiba, Parana - Brazil
[7] Univ Estadual Campinas, Campinas, SP - Brazil
[8] Univ Fed Minas Gerais, Belo Horizonte, MG - Brazil
[9] Univ Fed Sao Paulo, Sao Paulo - Brazil
[10] Santa Casa Med Sch, Sao Paulo - Brazil
[11] Clin Ruiz Puebla, Puebla - Mexico
[12] Hosp Salvador, Santiago - Chile
[13] Asociac Espanola Primera Socorros Mutuos, Montevideo - Uruguay
[14] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 - USA
[15] Albert Einstein Canc Ctr, New York, NY - USA
[16] Univ Med Ctr, Freiburg - Germany
[17] Stanford Univ, Stanford, CA 94305 - USA
[18] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY - USA
[19] Kings Coll London, Sch Med, London WC2R 2LS - England
[20] Hannover Med Sch, Hannover - Germany
[21] Harvard Univ, Sch Med, Boston, MA - USA
[22] St Jude Childrens Res Hosp, Memphis, TN 38105 - USA
[23] Univ Roma Tor Vergata, Rome - Italy
[24] Santa Lucia Fdn, Rome - Italy
[25] Erasmus Univ, Med Ctr, Rotterdam - Netherlands
[26] Univ Valencia, Sch Med, Valencia - Spain
[27] Univ Sao Paulo, Med Sch Ribeirao Preto, BR-14048900 Ribeirao Preto, SP - Brazil
Total Affiliations: 27
Document type: Journal article
Source: ANNALS OF HEMATOLOGY; v. 93, n. 12, p. 2001-2010, DEC 2014.
Web of Science Citations: 14
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. (AU)

FAPESP's process: 98/14247-6 - Center for Research on Cell-Based Therapy
Grantee:Marco Antonio Zago
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC