Infection Burden in Mismatched Unrelated Donor Hematopoietic Cell Transplantation: Results from the ACCESS Trial

Human leukocyte antigen (HLA)-mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) has emerged as an effective therapy for adult patients with hematologic malignancies. The MMUD ACCESS Trial (NCT04904588), which incorporated post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis, demonstrated combined overall survival of 81% in enrolled patients, 59% who were ethnically diverse. Given PTCy is also associated with significant bacterial and viral infections, we defined infection burden in the full adult cohort (N=268) using infections graded according to an international standard (CTCAE, Common Terminology Criteria for Adverse Events, version 5.0). Infection density (number of infections per 100 days at risk), cumulative incidence of infection, and frequency of pathogen types were categorized by post-HCT time, conditioning intensity, level of donor HLA mismatch, and presence of acute GvHD. Of 465 recorded CTCAE grade 2-5 infections recorded in 183 (68%) adults, 176 (38%) infections were significant or life-threatening and most infections (296, 64%) occurred within the first 100 days. Infection density at Days 0-30 was significantly higher than at other times and was similar by conditioning and level of HLA mismatch as were pathogen types and isolates. Multivariable analysis showed that acute GvHD is significantly associated with infection. Lastly, 21 (7.8%) patients died from infection. Results show significant infection burden using standard dose PTCy in the MMUD HCT setting, irrespective of conditioning and level of donor HLA mismatch, and will serve as a benchmark for trials investigating reducing infection burden following MMUD HCT.