domingo, 7 de agosto de 2016

Clinical Utility of Next Generation Sequencing for Oncogenic Mutations in AML Patients Undergoing Allogeneic Stem Cell Transplantation. - PubMed - NCBI

Clinical Utility of Next Generation Sequencing for Oncogenic Mutations in AML Patients Undergoing Allogeneic Stem Cell Transplantation. - PubMed - NCBI



 2016 Jul 28. pii: S1083-8791(16)30254-3. doi: 10.1016/j.bbmt.2016.07.018. [Epub ahead of print]

Clinical Utility of Next Generation Sequencing for Oncogenic Mutations in AML Patients Undergoing Allogeneic Stem Cell Transplantation.

Abstract

To determine the association of somatic mutations in acute myeloid leukemia (AML) with risk of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT), we retrospectively studied pre-transplant genetic profiles obtained from next generation sequencing of 26 genes in 112 adult AML patients who underwent alloHSCT. Univariable and multivariable regression analyses were used to assess the association between the presence of a pathogenic mutation and risk of relapse after alloHSCT. Eighty-six percent (96/112) of patients had at least 1 pathogenic mutation. Mutations in TP53, WT1, and FLT3-ITD were associated with an increased risk of relapse after alloHSCT (adjusted HR [aHR] 2.90, P = .009, aHR 2.51, P = .02, and aHR 1.83, P = .07, respectively). DNMT3A mutation in the absence of FLT3-ITD and NPM1 mutations was associated with a lower relapse risk (aHR 0.22, P = .04). Comparison of pre- and post-alloHSCT genetic profiles showed clonal evolution in 6/6 patients, including acquisition of actionable mutations in 4 patients. In summary, genetic profiling is useful for assessing relapse risk in AML patients undergoing alloHSCT, and may identify patients in need of strategies to reduce this risk. Clonal evolution is present at post-alloHSCT relapse and repeat genetic profiling may uncover acquired actionable mutations.
Copyright © 2016. Published by Elsevier Inc.

KEYWORDS:

Allogeneic stem cell transplant; acute myeloid leukemia; next generation sequencing; relapse

[PubMed - as supplied by publisher]

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