HLA-matched versus haploidentical donor transplantation with post-transplant cyclophosphamide: a study on behalf of the donor/source working group of the Japanese society for transplantation and cellular therapy.

Post-transplant cyclophosphamide (PTCy) is now being increasingly applied to HLA-matched donor (MD) transplantation. Prior studies in Western countries have demonstrated that allogeneic hematopoietic cell transplantation (allo-HCT) employing PTCy yields better outcomes with HLA-matched donors (MDs) than with haploidentical donors (HIDs). However, the effect of HLA mismatch may differ among racial groups. We retrospectively analyzed adult patients with hematological malignancies who underwent their first allo-HCT with PTCy from MDs or HIDs registered to the Japanese registry database between 2013 and 2021. Among 63 (related, n = 33; unrelated, n = 30) and 1261 patients who received MD and HID allo-HCT with PTCy, 50 (related, n = 30; unrelated, n = 20) and 100 patients were assigned to MD and HID groups by 1:2 propensity score matching (PSM). The results showed that MD recipients had better neutrophil recovery (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.04–2.10; P = 0.031) and lower risk of non-relapse mortality (NRM) (HR, 0.19; 95% CI, 0.05–0.81; P = 0.024) than HID recipients. Multivariable analyses in the entire cohort before PSM confirmed these findings. Fatal infection was the primary cause of NRM in the HID group. This study is the first to demonstrate that, within a homogeneous Asian cohort, MD may have an advantage over HID in PTCy-based allo-HCT in facilitating neutrophil engraftment and reducing the risk of NRM.