Risk Factors for Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation with Umbilical Cord Blood and Matched Sibling Donors

• Distinct incidences and risks of GVHD exist for UCB and MSD allografts.
• Impact of GVHD on post-transplant outcomes varies by donor source.
• Better HLA match is associated with less severe aGVHD in dUCB transplantation.

Allogeneic hematopoietic cell transplantation is often complicated by graft-versus-host disease (GVHD). We analyzed the incidences and risk factors for acute (aGVHD) and chronic GVHD (cGVHD), and their impact on disease relapse and survival, among recipients of single umbilical cord blood (sUCB, n = 295), double umbilical cord blood (dUCB, n = 416), and matched sibling donor (MSD, n = 469) allografts. The incidences of grades II to IV aGVHD and chronic GVHD among dUCB, sUCB, and MSD were 56% and 26%, 26% and 7%, 37% and 40%, respectively. Development of aGVHD had no effect on relapse, nonrelapse mortality, or overall survival among cord blood recipients, but it was associated with worse nonrelapse mortality and survival in MSD recipients. Development of cGVHD was only associated with lower relapse in dUCBT. In multivariate analysis of GVHD incidence, age > 18 years was associated with higher incidence of aGVHD and cGVHD across all cohorts. In both UCB cohorts worse HLA match and prior aGVHD were associated with higher risks of aGVHD and cGVHD, respectively. Nonmyeloablative conditioning limited the risk of aGVHD compared with myeloablative conditioning in dUCB recipients. Cyclosporine A and mycophenolate mofetil as GVHD prophylaxis lowered the risk of cGVHD, compared with steroids with cyclosporine A, among sUCB recipients. This large contemporary analysis suggests distiinct risks and consequences of GVHD for UCB and MSD recipients. Limiting the severity of aGVHD remains important in all groups. Increasing the cord blood inventory or developing strategies that reduce the cell-dose threshold and thereby increase the chance of identifying an adequately dosed, better HLA-matched sUCB unit may further limit risks of aGVHD after UCB transplantation.