Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma
Open accessAbstract
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.
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Patients with CHIP and solid tumors or lymphoma have an increased risk of therapy-related myeloid neoplasms after treatment for the primary disease.
“Several studies have found that patients with CHIP and solid tumors or lymphoma have an increased risk of these therapy-related myeloid neoplasms after treatment for the primary disease 73–75.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [73]
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- Authors
- Gibson, C. J., Lindsley, R. C., Tchekmedyian, V., Mar, B. G., Shi, J., Jaiswal, S., Bosworth, A., Francisco, L., He, J., Bansal, A., Morgan, E. A., Lacasce, A. S., Freedman, A. S., Fisher, D. C., Jacobsen, E., Armand, P., Alyea, E. P., Koreth, J., Ho, V., Soiffer, R. J., Antin, J. H., Ritz, J., Nikiforow, S., Forman, S. J., Michor, F., Neuberg, D., Bhatia, R., Bhatia, S., & Ebert, B. L.
- Affiliations
- Brigham and Women's Hospital (US)
- 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,...
- Corresponding author
- Ebert, Benjamin L.
- ORCID
- Gibson, Christopher J.
- Lindsley, R. Coleman
- Tchekmedyian, Vatche
- Mar, Brenton G.
- Shi, Jiantao
- Jaiswal, Siddhartha
- Bosworth, Alysia
- Francisco, Liton
- He, Jianbo
- Bansal, Anita
- Morgan, Elizabeth A.
- Lacasce, Ann S.
- Freedman, Arnold S.
- Fisher, David C.
- Jacobsen, Eric
- Armand, Philippe
- Alyea, Edwin P.
- Koreth, John
- Ho, Vincent
- Soiffer, Robert J.
- Antin, Joseph H.
- Ritz, Jerome
- Nikiforow, Sarah
- Forman, Stephen J.
- Neuberg, Donna
- Ebert, Benjamin L.
- Venue
- Journal of Clinical Oncology
- Published
- 2017-05-10
- Volume
- 35
- Issue
- 14
- Pages
- 1598-1605
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC5455707
- OpenAlex
- W2574119868
- Cited by
- 480
- References
- 24
- Citations by year
- 2026: 35 · 2025: 40 · 2024: 68 · 2023: 56 · 2022: 58 · 2021: 61 · 2020: 52 · 2019: 47 · 2018: 44 · 2017: 18
- FWCI
- 33.87
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL082945, T32HL116324)
- National Cancer Institute (U54CA193461, P50CA107399, K08CA204734, P50CA206963, P01CA066996, P30CA006516)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK099808)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- clonal hematopoiesis of indeterminate potential, autologous stem cell transplantation, lymphoma, therapy-related myeloid neoplasms, myelodysplastic syndrome, acute myeloid leukemia, somatic mutations, Hodgkin's disease, non-Hodgkin lymphoma, overall survival, cardiovascular mortality, pre-transplant risk stratification
- MeSH terms
- Protein Phosphatase 2C, DNA Methyltransferase 3A, Adolescent, Adult, Aged, Clone Cells, DNA (Cytosine-5-)-Methyltransferases, DNA Mutational Analysis, DNA-Binding Proteins, Female, Hematopoiesis, Hodgkin Disease, Humans, Lymphoma, Non-Hodgkin, Male, Middle Aged, Myelodysplastic Syndromes, Proto-Oncogene Proteins, Repressor Proteins, Transplantation, Autologous, Leukemia, Myeloid, Acute, Survival Rate, Tumor Suppressor Protein p53, Neoplasms, Second Primary, Hematopoietic Stem Cell Transplantation, Dioxygenases, Exome
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