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Cited by 223Hematopoietic Stem Cell TransplantationAcute Myeloid Leukemia ResearchTransplantation: Methods and Outcomes

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation

Frick, Mareike, Chan, Willy, Arends, Christopher Maximilian, Hablesreiter, Raphael, Halik, Adriane, Heuser, Michael, Michonneau, David, Blau, Olga, Hoyer, Kaja, Christen, Friederike, Galan-Sousa, Joel, Noerenberg, Daniel, Wais, Verena, Stadler, Michael, Yoshida, Kenichi, Schetelig, Johannes, Schuler, Esther, Thol, Felicitas, Clappier, Emmanuelle, Christopeit, Maximilian, Ayuk, Francis, Bornhäuser, Martin, Blau, Igor Wolfgang, Ogawa, Seishi, Zemojtel, Tomasz, Gerbitz, Armin, Wagner, Eva M., Spriewald, Bernd M., Schrezenmeier, Hubert, Kuchenbauer, Florian, Kobbe, Guido, Wiesneth, Markus, Koldehoff, Michael, Socié, Gérard, Kroeger, Nicolaus, Bullinger, Lars, Thiede, Christian, Damm, Frederik·2019·Journal of Clinical Oncology
DOI 10.1200/jco.2018.79.2184
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Abstract

PURPOSE: Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). METHODS: We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS). RESULTS: A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434). CONCLUSION: Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.

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Metadata

Authors
Frick, M., Chan, W., Arends, C. M., Hablesreiter, R., Halik, A., Heuser, M., Michonneau, D., Blau, O., Hoyer, K., Christen, F., Galan-Sousa, J., Noerenberg, D., Wais, V., Stadler, M., Yoshida, K., Schetelig, J., Schuler, E., Thol, F., Clappier, E., Christopeit, M., Ayuk, F., Bornhäuser, M., Blau, I. W., Ogawa, S., Zemojtel, T., Gerbitz, A., Wagner, E. M., Spriewald, B. M., Schrezenmeier, H., Kuchenbauer, F., Kobbe, G., Wiesneth, M., Koldehoff, M., Socié, G., Kroeger, N., Bullinger, L., Thiede, C., & Damm, F.
Affiliations
  • Humboldt-Universität zu Berlin (DE)
  • Medizinische Hochschule Hannover (DE)
  • Inserm (FR)
  • University Hospital Ulm (DE)
  • Kyoto University (JP)
  • University Hospital Carl Gustav Carus (DE)
  • Heinrich Heine University Düsseldorf (DE)
  • Hôpital Saint-Louis (FR)
  • Universität Hamburg (DE)
  • Berlin Institute of Health (BIH) Core Genomics Facility, Charité, University Medical Center, Berlin, Germany
  • Johannes Gutenberg University Mainz (DE)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • German Red Cross (DE)
  • Essen University Hospital (DE)
  • David Michonneau and Gérard Socié, INSERM U1160, Institut Universitaire d’Hematologie, Paris/University Paris Diderot, Paris, France
  • University Hospital Eppendorf, Hamburg, Germany
  • German Cancer Research Center (DE)
  • Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2019-02-10
Volume
37
Issue
5
Pages
375-385
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2018.79.2184
OpenAlex
W2899711966
Cited by
223
References
46
Citations by year
2026: 12 · 2025: 14 · 2024: 31 · 2023: 28 · 2022: 38 · 2021: 39 · 2020: 36 · 2019: 23
FWCI
17.77
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Clinical Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders
Japan Society for the Promotion of Science (19H05656, 15H05909)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
Keywords
clonal hematopoiesis of indeterminate potential, allogeneic hematopoietic stem cell transplantation, donor eligibility, chronic graft-versus-host disease, relapse and progression, clonal mutations, clonal expansion, donor cell leukemia, overall survival
MeSH terms
Age Factors, Aged, Female, Gene Frequency, Graft vs Host Disease, Hematopoiesis, Hematopoietic Stem Cells, Humans, Male, Middle Aged, Mutation, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Hematologic Neoplasms, Unrelated Donors

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