Allogeneic Transplantation in First Remission Improves Outcomes Irrespective of FLT3-ITD Allelic Ratio in FLT3-ITD-Positive Acute Myelogenous Leukemia.

Autor: Oran B; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: boran@mdanderson.org., Cortes J; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Beitinjaneh A; Department of Medicine, University of Virginia Health System, Charlottesville, Virginia., Chen HC; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas., de Lima M; Department of Medicine-Hematology and Oncology, University Hospitals and Case Western Reserve University, Cleveland, Ohio., Patel K; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Ravandi F; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Wang X; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Brandt M; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Andersson BS; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas., Ciurea S; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas., Santos FP; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., de Padua Silva L; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas., Shpall EJ; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas., Champlin RE; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kantarjian H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas., Borthakur G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jazyk: angličtina
Zdroj: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2016 Jul; Vol. 22 (7), pp. 1218-1226. Date of Electronic Publication: 2016 Apr 04.
DOI: 10.1016/j.bbmt.2016.03.027
Abstrakt: The adverse prognosis of internal tandem duplication in the FMS-like tyrosine kinase 3 gene(s) (FLT3-ITD) in patients with acute myelogenous leukemia (AML) may depend on allelic burden. We compared postremission treatment with chemotherapy and hematopoietic stem cell transplantation (HSCT) in 169 FLT3-ITDmut intermediate cytogenetic risk AML patients with allelic ratio evaluable at diagnosis who achieved first complete remission (CR1) with induction therapy. To minimize selection bias, the analysis was limited to patients who remained in CR1 for at least 4 months (median time to HSCT) after achieving CR1, and propensity score matching was implemented. Sensitivity analysis including patients who remained in CR1 for at least 3 months was applied as well. HSCT in CR1 was associated with longer relapse-free survival (RFS) and overall survival (OS), with 3-year estimated rates of 18% and 24%, respectively (P < .001), for patients receiving chemotherapy and 46% and 54%, respectively (P < .001), for those undergoing HSCT. Multivariate regression models showed that HSCT remained statistically significant with improved RFS and OS independent of FLT3-ITD allelic ratio and NPM1 status. Irrespective of postremission therapy, relapse remains the main reason for treatment failure, with a 3-year incidence of 68% in chemotherapy recipients versus 41% in HSCT recipients. Allogeneic HSCT improved disease outcomes compared with chemotherapy after propensity score matching was applied. The improvement observed for RFS (hazard ratio [HR], 0.55; P = .09) and OS (HR, 0.58; P = .10) with HSCT as postremission therapy in patients who remained in CR1 for at least 4 months did not reach statistical significance; however, the sensitivity analyses including patients who remained in CR1 for at least 3 months showed significant improvement in both RFS (HR, 0.31; P = .002) and OS (HR, 0.27; P = .02) after propensity score matching. Our results indicate that HSCT in CR1 for AML FLT3-ITDmut patients is associated with longer RFS and OS. Innovative transplantation strategies to improve relapse incidence are urgently needed.
(Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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