Impact of graft-versus-host disease on outcomes of cord blood transplantation according to HLA disparity and its prophylaxis type.

This study evaluated the impact of acute graft-versus-host disease (aGVHD) on cord blood transplantation (CBT) outcomes based on human leukocyte antigen (HLA) disparity and GVHD prophylaxis type. Data from 4,196 adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome were analyzed. Patients were classified by HLA mismatch (8/8-6/8, 5/8, and 4/8-2/8) and further by GVHD prophylaxis type (methotrexate [MTX] or mycophenolate mofetil [MMF]). The impact of aGVHD was assessed using a time-dependent Cox model. Grade I-II aGVHD improved overall survival (OS) in all groups, regardless of HLA mismatches or prophylaxis type. However, grade III-IV aGVHD worsened OS across MMF groups, while in MTX groups, it was unfavorable only in the HLA 8/8-6/8-matched group (HR 1.6, P = 0.01). Grade III-IV aGVHD increased non-relapse mortality (NRM) across all groups but was more pronounced in HLA 4/8-2/8-matched patients receiving MMF. Notably, relapse risk decreased in HLA 4/8-2/8-matched patients with MTX prophylaxis, partially offsetting the negative impact of grade III-IV aGVHD on NRM. These findings suggest that the impact of aGVHD varies with HLA mismatches and prophylaxis type. MTX prophylaxis may mitigate the adverse effects of severe aGVHD in highly mismatched cases, unlike MMF prophylaxis. Careful donor selection considering HLA mismatches is essential when using MMF prophylaxis to manage severe aGVHD and reduce NRM risk.