Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma
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Published:2017-05-10
Issue:14
Volume:35
Page:1598-1605
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Gibson Christopher J.1, Lindsley R. Coleman1, Tchekmedyian Vatche1, Mar Brenton G.1, Shi Jiantao1, Jaiswal Siddhartha1, Bosworth Alysia1, Francisco Liton1, He Jianbo1, Bansal Anita1, Morgan Elizabeth A.1, Lacasce Ann S.1, Freedman Arnold S.1, Fisher David C.1, Jacobsen Eric1, Armand Philippe1, Alyea Edwin P.1, Koreth John1, Ho Vincent1, Soiffer Robert J.1, Antin Joseph H.1, Ritz Jerome1, Nikiforow Sarah1, Forman Stephen J.1, Michor Franziska1, Neuberg Donna1, Bhatia Ravi1, Bhatia Smita1, Ebert Benjamin L.1
Affiliation:
1. Christopher J. Gibson, R. Coleman Lindsley, Brenton G. Mar, Jiantao Shi, Ann S. Lacasce, Arnold S. Freedman, David C. Fisher, Eric Jacobsen, Philippe Armand, Edwin P. Alyea, John Koreth, Vincent Ho, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz, Sarah Nikiforow, Franziska Michor, and Donna Neuberg, Dana-Farber Cancer Institute; Jiantao Shi and Franziska Michor, Harvard T.H. Chan School of Public Health; Siddhartha Jaiswal, Elizabeth A. Morgan, and Benjamin L. Ebert, Brigham and Women’s Hospital,...
Abstract
Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood of otherwise healthy adults. We hypothesized that in patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at the time of ASCT would be associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related myeloid neoplasm (TMN), and other adverse outcomes. Methods We performed whole-exome sequencing on pre- and post-ASCT samples from 12 patients who developed TMN after autologous transplantation for Hodgkin lymphoma or non-Hodgkin lymphoma and targeted sequencing on cryopreserved aliquots of autologous stem-cell products from 401 patients who underwent ASCT for non-Hodgkin lymphoma between 2003 and 2010. We assessed the effect of CHIP at the time of ASCT on subsequent outcomes, including TMN, cause-specific mortality, and overall survival. Results For six of 12 patients in the exome sequencing cohort, mutations found in the TMN specimen were also detectable in the pre-ASCT specimen. In the targeted sequencing cohort, 120 patients (29.9%) had CHIP at the time of ASCT, which was associated with an increased rate of TMN (10-year cumulative incidence, 14.1% v 4.3% for those with and without CHIP, respectively; P = .002). Patients with CHIP had significantly inferior overall survival compared with those without CHIP (10-year overall survival, 30.4% v 60.9%, respectively; P < .001), including increased risk of death from TMN and cardiovascular disease. Conclusion In patients undergoing ASCT for lymphoma, CHIP at the time of transplantation is associated with inferior survival and increased risk of TMN.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
320 articles.
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