Transplantation Using Bone Marrow from a (very) HLA Mismatched Unrelated Donor in the Setting of Post-Transplant Cyclophosphamide Is Feasible and Expands Access to Underserved Minorities

Background Despite increasing donor options for allogeneic transplantation, including matched/mismatched related donors, matched unrelated donors and cord blood units, a proportion of patients do not find a donor. This is especially relevant in patients from racial/ethnic minorities. Post-transplant cyclophosphamide (PTCY) has successfully overcome barriers related to HLA-mismatching in the related donor setting. We hypothesized that transplantation with a mismatched unrelated donor (MMUD) using PTCY would be feasible and associated with high engraftment and acceptable GVHD incidence. Methods We performed a prospective Phase II study of MMUD bone marrow (BM) transplantation with PTCY for patients with hematologic malignancies. Patients with a suitable HLA matched related or URD were excluded. Patients received a fresh BM graft, followed by PTCY on days +3, +4, Sirolimus/MMF starting on Day+5. Matching for 4-7/8 at HLA-A, -B, -C, and –DRB1 was permitted. We enrolled 80 patients (40 full intensity conditioning [FIC]; 40 reduced intensity conditioning [RIC]) at 11 transplant centers in the U.S. between Dec 2016 and March 2019. Regimen intensity was at the center's discretion. Results Characteristics are shown in Table 1. Importantly, 48% of patients were non-white/Hispanic, 55% had an HCT-CI >2 and 34% had a KPS of 1 HLA allele, 59% were under 30. Overall survival and non-relapse mortality at 100 days were 92% and 5% in the FIC arm, and 90% and 7.5% in the RIC arm (Table 2). Neutrophil recovery was 98% in both arms, with no primary graft failure in the FIC arm, and 7.5% in the RIC arm. Peripheral blood donor chimerism was >75% at all timepoints. Acute GVHD grade III-IV at day 100 was relatively high at 25% in the FIC arm but very low at 2.6% in the RIC arm. Viral reactivations were high (Table 3). Conclusion These early (day 100) results of our prospective study show high rates of engraftment with acceptable rates of GVHD in recipients of MMUD transplantation with PTCY, despite a high degree of HLA mismatch. An important finding is that ethnic minorities represent almost 50% of the study population, showing that this approach expands access to patients in need of potentially curative therapy. BK and HHV-6 virus reactivation/infection were common, the clinical significance of which requires further study. Understanding the risks for and impact of graft failure and acute GVHD is being studied as follow up continues.