ABO Mismatch Adversely Affects GvHD In Recipients of HLA Matched Unrelated Marrow or Peripheral Blood but Not Single or Double Umbilical Cord Blood Transplants
Authors: Romee Rizwan , Weisdorf Daniel J. , Brunstein Claudio , Wagner John E. , Blazar Bruce R. , Majhail Navneet S. , Vercellotti Gregory M. , Miller Jeffrey S. , Arora Mukta 
Published: October 2019

Abstract
Abstract 226
Recent advances in hematopoietic cell transplant (HCT) have led to an increasing use of alternative donors and stem cell sources, including umbilical cord blood (UCB). Despite these advances, graft-versus-host disease (GvHD) remains a major barrier to HCT: both acute GvHD (aGvHD) and chronic GVHD (cGvHD) are leading causes of early and late transplant related mortality (TRM). ABO mismatches in HCT can be minor where donor B cells can produce anti-recipient isoagglutinins, major where recipient has preformed anti-donor isoagglutinins and mixed with a combination of minor and major mismatches. Several recent studies have postulated that minor ABO mismatches may function as minor histocompatibility antigens and have demonstrated an increased risk of aGvHD and cGvHD in recipients of ABO minor mismatched, but HLA-matched adult-unrelated donor (URD) HCT. Data on the effect of ABO mismatch in recipients of single and double UCB HCT are limited. We hypothesized that, since UCB -T and -B cells are postulated to be immunologically na•ve, ABO minor and mixed mismatches would not have a significant impact on GvHD in UCB HCT. We analyzed the impact of ABO mismatch on aGvHD and cGvHD in a retrospective cohort of recipients of single (N=208) and double (N=295) UCB and compared them to 6/6 HLA-matched adult- URD (N=124) recipients who underwent an allogeneic HCT (marrow or peripheral blood stem cells) at University of MN between Jan 2000 and Dec 2007. Amongst double UCB recipients, HLA-matching was determined by the worst matched unit and ABO status of both the cords was considered in the ABO matching. In 4–6/6 HLA matched UCB recipients, ABO minor and/ or mixed mismatch was not found to be associated with an increased risk of grade II-IV aGvHD or cGvHD. In contrast, minor and/ or mixed ABO mismatch was associated with 2.85 (95% CI: 1.27–6.40) times higher risk of grade II-IV aGvHD in URD group. Minor and/ or mixed ABO mismatch was also associated with three times (RR: 3.0, 95% CI: 1.02–8.81) higher risk of cGVHD in URD group. In the URD group, major ABO mismatch was also associated with almost 5 fold (RR: 4.7, 95% CI: 1.37–16.35) higher risk of cGvHD; major ABO mismatch did not have any impact on risk of aGvHD. This study reaffirms the recent in vitro results showing the potential of highly polymorphic ABO-glycosyltransferase peptides to act as minor histocompatibility antigens in URD HCT. ABO mismatch in UCB recipients does not impact aGvHD or cGvHD, which may be related to the presence of relatively na•ve and unprimed T-cells in the UCB grafts. There was no statistically significant difference in overall survival, TRM or disease free survival in ABO matched vs mismatched cohorts in any of the above groups. If confirmed in other independent datasets, these data suggest that allogeneic HCT could be safely performed across ABO barriers using UCB as the source of stem cells without an increase in the risk of acute or chronic GvHD. However caution needs to be advised for recipients of minor or mixed ABO mismatched adult-URD transplantation.

Disclosures:
Vercellotti: Sangart: Consultancy, Research Funding.