Over the past decade, advances in hematopoietic stem cell transplantation (HSCT) have enabled older individuals to undergo the procedure as well as to serve as donors. Recently, aging has been linked with the development of age-related clonal hematopoiesis (ARCH), defined as the gradual clonal expansion of hematopoietic stem and progenitor cells (HSPC) carrying recurrent disruptive genetic variants in individuals without a diagnosis of hematologic malignancy. Here we will review the implications of ARCH in the context of HSCT.
ARCH is highly prevalent in the general population and commonly involves genes that are recurrently mutated in hematologic malignancies. Nevertheless, the vast majority of individuals with ARCH will not develop overt hematologic disease in their lifetime. The presence of ARCH may increase the risk of therapy-related myeloid neoplasms (t-MN) in individuals undergoing autologous HSCT. In the setting of allogeneic HSCT, ARCH present in the donor may contribute to adverse outcomes such as unexplained cytopenias posttransplant and donor cell leukemia.
A better understanding of the hematopoietic milieu of HSCT recipients and of the importance of ARCH in the context of the replicative pressures imposed on transplanted HSPCs is needed in order to optimize conditioning regimens, donor selection and clinical outcomes post-HSCT.
aPrincess Margaret Cancer Centre, University Health Network (UHN)
bDivision of Medical Oncology and Hematology, Department of Medicine, UHN
cDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada
Correspondence to Jean C.Y. Wang, MD, PhD, FRCPC, Princess Margaret Cancer Centre, University Health Network (UHN), MaRS PMCRT 8-363, 101 College Street, Toronto, ON M5G 1L7, Canada. Tel:/fax: +1 416 581 7475; e-mail: firstname.lastname@example.org