Infections after allogenic transplant with post-transplant cyclophosphamide: impact of donor HLA-matching

Abstract Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PT-Cy) as GVHD prophylaxis is largely unknown. Study aims were to estimate incidence of pre-engraftment blood-stream infections (PE-BSI) and viral infections [VIs; Cytomegalovirus (CMV), adenovirus (ADV), human herpes virus-6 (HHV6) and BK-polyomavirus hemorrhagic-cystitis (BKPyV-HC)], their predictive factors and infection-related mortality (IRM), after HSCT with PT-Cy. We analyzed 235 patients: 62%, 21% and 17% received haploidentical (haplo), matched-unrelated donor (MUD) and matched-related donor (MRD), respectively. Overall, 72 patients had 77 PE-BSI episodes at a median time of 13-days after HSCT: cumulative incidence function (CIF) at 28-days was 32%, without differences among donor types (p=0.988). By multivariate analysis, CIF of PE-BSI was higher in subjects with severe neutropenia before HSCT [adjusted hazard ratio (AHR) =2.90] and in multi-drug resistant Gram-negative bacteria rectal carriers (AHR=2.68). IRM at 30-days was 5%, without differences by donor type (p=0.106). Overall, 208 patients experienced ≥1 VIs (first occurrence among CMV, HHV6, ADV, BKPyV-HC) at median time of 20-days after HSCT: CIF at 90-days was 91%, significantly higher in MUD and haplo (p=0.0089). By multivariate analysis, also acute-GVHD grade≥2 (AHR=1.32) and host/donor CMV-serology mismatch [pos/pos vs neg/neg: AHR=2.95, pos/neg vs neg/neg: AHR=2.41, neg/pos vs neg/neg: AHR=2.35] affected VIs occurrence. IRM at 180-days was 8%, without differences among donor types (p=0.106). In conclusion, study's results did not show a significant impact of donor type on PE-BSIs incidence; conversely MUD and haploidentical transplants retained a higher occurrence of VIs in the early phase after HSCT.