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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

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...

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Main Authors: Ho, Anthony Dick (Author) , Schetelig, Johannes (Author) , Bochtler, Tilmann (Author) , Schaich, Markus (Author) , Schäfer-Eckart, Kerstin (Author) , Hänel, Mathias (Author) , Rösler, Wolf (Author) , Einsele, Hermann (Author) , Kaufmann, Martin (Author) , Serve, Hubert (Author) , Berdel, Wolfgang E. (Author) , Stelljes, Matthias (Author) , Mayer, Jiri (Author) , Reichle, Albrecht (Author) , Baldus, Claudia D. (Author) , Schmitz, Norbert (Author) , Kramer, Michael (Author) , Röllig, Christoph (Author) , Bornhäuser, Martin (Author) , Thiede, Christian (Author) , Ehninger, Gerhard (Author)
Format: Article (Journal)
Language:English
Published: 2016
In: Biology of blood and marrow transplantation
Year: 2015, Volume: 22, Issue: 3, Pages: 462-469
ISSN:1523-6536
DOI:10.1016/j.bbmt.2015.10.023
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbmt.2015.10.023
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1083879115007260
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Author Notes:Anthony 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
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Summary: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 (HRFLT3-ITD and LRFLT3-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 HRFLT3-ITD AML who received alloHCT as consolidation treatment compared with patients who received consolidation chemotherapy. Patients with LRFLT3-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 LRFLT3-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 HRFLT3-ITD AML and in patients with LRFLT3-ITD AML and wild-type NPM1.
Item Description:Available online 10 November 2015
Gesehen am 14.05.2020
Physical Description:Online Resource
ISSN:1523-6536
DOI:10.1016/j.bbmt.2015.10.023

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