Outcomes of HLA-DPB1 Mismatch in Patients Receiving Post-Transplant Cyclophosphamide for Graft Versus Host Disease Prophylaxis

Introduction Non-permissive HLA-DPB1 mismatch is associated with increased risk of acute graft versus host disease (GVHD), non-relapse mortality (NRM) and inferior overall survival (OS) in matched unrelated allogenic stem cell transplant (alloSCT) recipients. Post-transplant cyclophosphamide (PTCY) is the new standard GVHD prophylaxis regimen. Here, we describe our experience of DPB1 mismatch including allelic level in patients undergoing unrelated matched (MUD) or mismatched (MMUD) alloSCT with PTCY. Methods We retrospectively reviewed patients from July 2020 to April 2023 who underwent MUD or MMUD alloSCT and received PTCY with tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Comparative analysis was performed among cohorts determined by DP match status and DP expression levels separately. Kaplan–Meier and log-rank tests were used to estimate OS. NRM and relapse incidence (RI) were calculated using competing risk analysis. R 4.3.1 was used for statistical analyses. Results A total of 25 patients [17 (68%) males] were evaluated. Median age at transplant was 62 years (range 30 - 76 years). Eight patients (32%) were DP matched, while 6 (25%) and 11 (44%) patients were DP permissive (P-MM) and non-permissive mismatch (NP-MM), respectively (Table1).In DP NP-MM cohort, 3 patients (27%) developed grade 2 acute GVHD (Skin only required systemic steroid), however none developed steroid refractory GVHD (SR-GVHD). In DP matched cohort, 2 patients (25%) developed grade 2 GVHD with one patient had gastrointestinal SR-GVHD. One patient each in DP NP-MM and DP matched cohorts had moderate-severe chronic GVHD, however the latter did not require systemic therapy.Of the total 9 patients with single DP allele mismatch, 6 (67%) had favorable expression. The DP double allele mismatch group had higher incidence of acute GVHD (57%, 4 of 7 patients) compared to DP match (2 of 8 patients, 25%), DP unfavorable expression (1 of 3 patients, 33%) and none in favorable expression cohorts. No chronic GVHD was noticed in either favorable or unfavorable expression groups.Median follow-up of the entire cohort after alloSCT was 11.4 months (95% CI 7.6 – 36.6 months). Survival at 2-years was similar among DP NP-MM (51.9%) and DP matched cohorts (53.6%) compared to the DP P-MM cohort (83.3%, P = 0.82) (Figure 1). NRM at 1-year after alloSCT was 14.6% vs. 0% vs. 39.4% in the DP match, DP P-MM and NP-MM groups respectively (P = 0.36) (Figure 2). Conclusion PTCY based GVHD prophylaxis is an effective regimen in reducing acute and chronic GVHD for patients with DPB1 non-permissive mismatch and unfavorable expression. There is a trend toward better transplant outcomes in DPB1 permissive mismatch, compared to DPB1 matched and non-permissive mismatch.