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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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| Authors: | Antonio R Lucena-Araujo Haesook T Kim Rafael H Jacomo Raul A Melo Rosane Bittencourt Ricardo Pasquini Katia Pagnano Evandro M Fagundes Maria de Lourdes Chauffaille Carlos S Chiattone Ana Silvia Lima Guillermo Ruiz-Argüelles Maria Soledad Undurraga Lem Martinez Hau C Kwaan Robert Gallagher Charlotte M Niemeyer Stanley L Schrier Martin S Tallman David Grimwade Arnold Ganser Nancy Berliner Raul C Ribeiro Francesco Lo-Coco Bob Löwenberg Miguel A Sanz Eduardo M Rego |
| Institution: | 1. Medical School of Ribeir?o Preto, Ribeirao Preto, Brazil 2. Center for Cell Based Therapy, Ribeirao Preto, Brazil 3. Dana-Farber Cancer Institute, Boston, MA, USA 4. Funda??o HEMOPE, Recife, Brazil 5. Federal University of Rio Grande do Sul, Porto Alegre, Brazil 6. Federal University of Paraná, Curitiba, Brazil 7. University of Campinas, Campinas, Brazil 8. Federal University of Minas Gerais, Belo Horizonte, Brazil 9. Federal University of Sao Paulo, Sao Paulo, Brazil 10. Santa Casa Medical School, Sao Paulo, Brazil 11. Clínica Ruiz de Puebla, Puebla, Mexico 12. Hospital del Salvador, Santiago, Chile 13. Asociación Espa?ola Primera de Socorros Mutuos, Montevideo, Uruguay 14. Northwestern University Feinberg School of Medicine, Chicago, IL, USA 15. Albert Einstein Cancer Center, New York, NY, USA 16. University Medical Center, Freiburg, Germany 17. Stanford University, Stanford, CA, USA 18. Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College, New York, NY, USA 19. King’s College London School of Medicine, London, UK 20. Hannover Medical School, Hannover, Germany 21. Harvard Medical School, Boston, MA, USA 22. St. Jude Children’s Research Hospital, Memphis, TN, USA 23. University Tor Vergata, Rome, Italy 24. Santa Lucia Foundation, Rome, Italy 25. Erasmus University Medical Center, Rotterdam, The Netherlands 26. Valencia University Medical School, Valencia, Spain 27. Medical School of Ribeirao Preto and Center for Cell Based Therapy, University of S?o Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, 14048-900, Brazil |
| 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?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?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. |
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