Role of donor clonal hematopoiesis in allogeneic hematopoietic stem-cell transplantation

Item Type:	Article
Title:	Role of donor clonal hematopoiesis in allogeneic hematopoietic stem-cell transplantation
Creators Name:	Frick, M. and Chan, W. and Arends, C.M. and Hablesreiter, R. and Halik, A. and Heuser, M. and Michonneau, D. and Blau, O. and Hoyer, K. and Christen, F. and Galan-Sousa, J. and Noerenberg, D. and Wais, V. and Stadler, M. and Yoshida, K. and Schetelig, J. and Schuler, E. and Thol, F. and Clappier, E. and Christopeit, M. and Ayuk, F. and Bornhäuser, M. and Blau, I.W. and Ogawa, S. and Zemojtel, T. and Gerbitz, A. and Wagner, E.M. and Spriewald, B.M. and Schrezenmeier, H. and Kuchenbauer, F. and Kobbe, G. and Wiesneth, M. and Koldehoff, M. and Socié, G. and Kroeger, N. and Bullinger, L. and Thiede, C. and Damm, F.
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.
Keywords:	Age Factors, Gene Frequency, Graft vs Host Disease, Hematologic Neoplasms, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Mutation, Retrospective Studies, Homologous Transplantation, Treatment Outcome, Unrelated Donors
Source:	Journal of Clinical Oncology
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology (ASCO)
Volume:	37
Number:	5
Page Range:	375-385
Date:	10 February 2019
Official Publication:	https://doi.org/10.1200/JCO.2018.79.2184
PubMed:	View item in PubMed

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