Journal article
Clonal hematopoiesis in donors and long-term survivors of related allogeneic hematopoietic stem cell transplantation.
- Boettcher S Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
- Wilk CM Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
- Singer J Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
- Beier F Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
- Burcklen E Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
- Beisel C Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
- Ventura Ferreira MS Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
- Gourri E Blood Transfusion Service Zurich, Zurich, Switzerland; and.
- Gassner C Blood Transfusion Service Zurich, Zurich, Switzerland; and.
- Frey BM Blood Transfusion Service Zurich, Zurich, Switzerland; and.
- Schanz U Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
- Skoda RC Department of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.
- Ebert BL Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
- Brummendorf TH Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
- Beerenwinkel N Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
- Manz MG Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
- 2020-03-18
Published in:
- Blood. - 2020
English
Clonal hematopoiesis (CH) is associated with age and an increased risk of myeloid malignancies, cardiovascular risk, and all-cause mortality. We tested for CH in a setting where hematopoietic stem cells (HSCs) of the same individual are exposed to different degrees of proliferative stress and environments, ie, in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their respective related donors (n = 42 donor-recipient pairs). With a median follow-up time since allo-HSCT of 16 years (range, 10-32 years), we found a total of 35 mutations in 23 out of 84 (27.4%) study participants. Ten out of 42 donors (23.8%) and 13 out of 42 recipients (31%) had CH. CH was associated with older donor and recipient age. We identified 5 cases of donor-engrafted CH, with 1 case progressing into myelodysplastic syndrome in both donor and recipient. Four out of 5 cases showed increased clone size in recipients compared with donors. We further characterized the hematopoietic system in individuals with CH as follows: (1) CH was consistently present in myeloid cells but varied in penetrance in B and T cells; (2) colony-forming units (CFUs) revealed clonal evolution or multiple independent clones in individuals with multiple CH mutations; and (3) telomere shortening determined in granulocytes suggested ∼20 years of added proliferative history of HSCs in recipients compared with their donors, with telomere length in CH vs non-CH CFUs showing varying patterns. This study provides insight into the long-term behavior of the same human HSCs and respective CH development under different proliferative conditions.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1182/blood.2019003079
- PMID 32181816
- Persistent URL
- https://folia.unifr.ch/global/documents/71971
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