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 Journal Article
| Authors: | Lucena-Araujo, A. R.; Kim, H. T.; Jacomo, R. H.; Melo, R. A.; Bittencourt, R.; Pasquini, R.; Pagnano, K.; Fagundes, E. M.; Chauffaille, M. D.; Chiattone, C. S.; Lima, A. S.; Ruiz-Arguelles, G.; Undurraga, M. S.; Martinez, L.; Kwaan, H. C.; Gallagher, R.; Niemeyer, C. M.; Schrier, S. L.; Tallman, M. S.; Grimwade, D.; Ganser, A.; Berliner, N.; Ribeiro, R. C.; Lo-Coco, F.; Löwenberg, B.; Sanz, M. A.; Rego, E. M. |
| Article 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 |
| 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: | inhibitor; arsenic trioxide; tyrosine kinase; mutations; acute promyelocytic leukemia; acute myelogenous leukemia; clinical-features; acute myeloid-leukemia; pml-rar-alpha; pml/rar-alpha; atra; prognostic implication; countries; risk-adapted treatment; developing; ic-apl; flt3-itd mutations; flt3-activating |
| Journal Title: | Annals of Hematology |
| Volume: | 93 |
| Issue: | 12 |
| ISSN: | 0939-5555 |
| Publisher: | Springer |
| Date Published: | 2014-12-01 |
| Start Page: | 2001 |
| End Page: | 2010 |
| Language: | English |
| ACCESSION: | WOS:000344803100006 |
| DOI: | 10.1007/s00277-014-2142-9 |
| PROVIDER: | wos |
| PUBMED: | 24981688 |
| Notes: | Article -- Source: Wos |
