Clonal Hematopoiesis in Related Allogeneic Transplant Donors: Implications for Screening and Management

Background: In hematopoietic cell transplantation (HCT), there is an increasing recognition of the risks of transferring clonal hematopoiesis from donors to recipients. It is unknown whether HCT centres screen for clonal hematopoiesis in related donors (RDs), and how such findings are managed. Methods: We conducted an international survey of 609 HCT centers to understand if HCT centres screen for CH, and whether candidates with this finding are excluded from donation. The survey consisted of questions about their approach to assessing otherwise healthy RDs with normal blood counts. Findings: The response rate was 280/609 (46%). Routine testing for CH is performed for monoclonal gammopathy of undetermined significance [MGUS] (18.9% of centres), monoclonal B-cell lymphocytosis [MBL] (5.0%), and gene sequencing for somatic mutations (3.6%). Bone marrow biopsies are performed in healthy RDs in 6% of responding centres, with an additional 6.7% performing this test in sub-groups, especially in older donors.  Respondents recalled detecting at least one case of MGUS (17.8% of respondents), MBL (9.9%) or cytogenetic abnormalities (7.7%).  Donor deferral was recommended in 62% of respondents if there were findings of MGUS, 60.4% for MBL, 74% for clonal cytogenetics, and 62.8% for somatic mutations. Interpretation:  An appreciable proportion of HCT centres routinely screen for disorders of CH in blood or marrow from RDs.  There is uncertainty about whether CH constitutes grounds for donor exclusion. We recommend the development of guidelines and standardization of screening for CH. Funding: Center for International Blood and Marrow Transplantation (CIBMTR) and National Marrow Donor Program (NMDP).   Declaration of Interest: Dr Seftel reports reports grants from Teva, personal fees from Shire, personal fees from Pfizer, personal fees from Jazz, personal fees from Amgen, outside the submitted work. Mr. Logan does not have any competing interests. Dr. Shah does not have any competing interests. Dr. Confer does not have any competing interests. Dr. Shaw does not have any competing interests. Dr. Switzer does not have any competing interests. Dr. Pulsipher does not have any competing interests. Ms. Kiefer does not have any competing interests. Ms. Kuxhausen does not have any competing interests. Dr. Lee does not have any competing interests. Dr. Burns does not have any competing interests. Dr. Chitphakdithai does not have any competing interests. Dr. O’Donnell does not have any competing interests. Ethical Approval: This survey was approved by the National Marrow Donor Program.