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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Frick M, Chan W, Arends CM, 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, Bornhaeuser M, Blau IW, Ogawa S, Zemojtel T, Gerbitz A, Wagner EM, Spriewald BM, Schrezenmeier H, Kuchenbauer F, Kobbe G, Wiesneth M, Koldehoff M, Socie G, Kroeger N, Bullinger L, Thiede C, Damm F
Zeitschrift: Journal of Clinical Oncology
Jahr der Veröffentlichung: 2019
Band: 37
Heftnummer: 5
Seitenbereich: 375-+
ISSN: 0732-183X


Abstract

PurposeClonal 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).MethodsWe 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).ResultsA 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).ConclusionAllogeneic 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.


Autor(en) der externen Einrichtung(en)
Charité - Universitätsmedizin Berlin
DRK-Blutspendedienst Baden-Württemberg - Hessen / German Red Cross Blood Donor Service Baden-Wuerttemberg – Hessen
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
Heinrich-Heine-Universität Düsseldorf
Kyoto University / 京都大学 Kyōto daigaku
Universität Duisburg-Essen (UDE)
Universitätsklinikum Carl Gustav Carus Dresden
Universitätsklinikum Hamburg-Eppendorf
Universitätsklinikum Ulm
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
University of Paris 7 - Denis Diderot / Université Paris VII Denis Diderot


Zitierweisen

APA:
Frick, M., Chan, W., Arends, C.M., Hablesreiter, R., Halik, A., Heuser, M.,... Damm, F. (2019). Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation. Journal of Clinical Oncology, 37(5), 375-+. https://dx.doi.org/10.1200/JCO.2018.79.2184

MLA:
Frick, Mareike, et al. "Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation." Journal of Clinical Oncology 37.5 (2019): 375-+.

BibTeX: 

Zuletzt aktualisiert 2019-12-03 um 09:23