Infection burden in mismatched unrelated donor hematopoietic cell transplantation: results from the ACCESS trial

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, which incorporated posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis, demonstrated a combined overall survival of 81% in enrolled patients, 59% of whom were from ethnically diverse groups. Given that 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 (Common Terminology Criteria for Adverse Events [CTCAE] 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 (aGvHD). Of 465 CTCAE grade 2 to 5 infections recorded in 183 (68%) adults, 176 (38%) were significant or life-threatening, and most (296 [64%]) occurred within the first 100 days. Infection density at days 0 to 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 aGvHD is significantly associated with infection. Finally, 21 (7.8%) patients died of 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 serve as a benchmark for trials investigating reducing infection burden after MMUD HCT. This trial was registered at www.clinicaltrials.gov as NCT04904588.