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

Ho AD, Schetelig J, Bochtler T, Schaich M, Schaefer-Eckart K, Haenel M, Rösler W, Einsele H, Kaufmann M, Serve H, Berde WE, Stelljes M, Mayer J, Reichle A, Baldus CD, Schmitz N, Kramer M, Roellig C, Bornhaeuser M, Thiede C, Ehninger G (2016)


Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 22

Pages Range: 462-9

Journal Issue: 3

DOI: 10.1016/j.bbmt.2015.10.023

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.

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APA:

Ho, A.D., Schetelig, J., Bochtler, T., Schaich, M., Schaefer-Eckart, K., Haenel, M.,... Ehninger, G. (2016). Allogeneic Stem Cell Transplantation Improves Survival in Patients with Acute Myeloid Leukemia Characterized by a High Allelic Ratio of Mutant FLT3-ITD. Biology of Blood and Marrow Transplantation, 22(3), 462-9. https://dx.doi.org/10.1016/j.bbmt.2015.10.023

MLA:

Ho, Anthony D., et al. "Allogeneic Stem Cell Transplantation Improves Survival in Patients with Acute Myeloid Leukemia Characterized by a High Allelic Ratio of Mutant FLT3-ITD." Biology of Blood and Marrow Transplantation 22.3 (2016): 462-9.

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