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Allogeneic Stem Cell Transplantation Improves Survival in Patients with Acute Myeloid Leukemia Characterized by a High Allelic Ratio of Mutant FLT3-ITD.

Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) as a postremission therapy in patients with FLT3-ITD-positive intermediate-risk acute myeloid leukemia (AML) remains controversial. FLT3-ITD mutations are heterogeneous with respect to allelic ratio, location, and length of the insertion, with a high mutant-to-wild-type ratio consistently associated with inferior prognosis. We retrospectively analyzed the role of alloHCT in first remission in relationship to the allelic ratio and presence or absence of nucleophosmin 1 mutations (NPM1) in the Study Alliance Leukemia AML2003 trial. FLT3-ITD mutations were detected in 209 patients and concomitant NPM1 mutations in 148 patients. Applying a predefined cutoff ratio of .8, AML was grouped into high- and low-ratio FLT3-ITD AML (HR(FLT3-ITD) and LR(FLT3-ITD)). Sixty-one patients (29%) were transplanted in first remission. Overall survival (OS) (HR, .3; 95% CI, .16 to .7; P = .004) and event-free survival (EFS) (HR, .4; 95% CI, .16 to .9; P = .02) were significantly increased in patients with HR(FLT3-ITD) AML who received alloHCT as consolidation treatment compared with patients who received consolidation chemotherapy. Patients with LR(FLT3-ITD) AML and wild-type NPM1 who received alloHCT in first remission had increased OS (HR, .3; 95% CI, .1 to .8; P = .02) and EFS (HR, .2; 95% CI, .1 to .8; P = .02), whereas alloHCT in first remission did not have a significant impact on OS and EFS in patients with LR(FLT3-ITD) AML and concomitant NPM1 mutation. In conclusion, our results provide additional evidence that alloHCT in first remission improves EFS and OS in patients with HR(FLT3-ITD) AML and in patients with LR(FLT3-ITD) AML and wild-type NPM1.
AuthorsAnthony D Ho, Johannes Schetelig, Tilmann Bochtler, Markus Schaich, Kerstin Schäfer-Eckart, Mathias Hänel, Wolf Rösler, Hermann Einsele, Martin Kaufmann, Hubert Serve, Wolfgang E Berdel, Matthias Stelljes, Jiri Mayer, Albrecht Reichle, Claudia D Baldus, Norbert Schmitz, Michael Kramer, Christoph Röllig, Martin Bornhäuser, Christian Thiede, Gerhard Ehninger, Study Alliance Leukemia
JournalBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 22 Issue 3 Pg. 462-9 (Mar 2016) ISSN: 1523-6536 [Electronic] United States
PMID26551637 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Chemical References
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
Topics
  • Adolescent
  • Adult
  • Alleles
  • Allografts
  • Disease-Free Survival
  • Female
  • Humans
  • Leukemia, Myeloid, Acute (enzymology, genetics, mortality, therapy)
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins (genetics)
  • Nucleophosmin
  • Stem Cell Transplantation
  • Survival Rate
  • fms-Like Tyrosine Kinase 3 (genetics)

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