Standard-dose PTCy enables mismatched-donor HCT but carries substantial early infection burden

Post-transplant cyclophosphamide (PTCy), followed by tacrolimus and mycophenolate, was used for graft-versus-host disease prophylaxis in the multicenter Phase 2 ACCESS trial (NCT04904588) of mismatched unrelated-donor hematopoietic cell transplantation for adults with hematologic malignancies (n=268 in this infection analysis). Investigators recorded 465 grade 2–5 infections in 183 patients (68%); 176 infections (38%) were severe or life-threatening, 64% occurred during the first 100 days, and 21 patients (7.8%) died from infection. Infection density peaked during days 0–30 and did not differ meaningfully by conditioning intensity or degree of HLA mismatch, while acute GvHD was independently associated with greater infection risk. These complications temper the ACCESS trial’s favorable survival results—approximately 81% combined 1-year OS—while establishing an important safety benchmark for reduced-dose PTCy and other infection-sparing strategies.