Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis

•In a Center for International Blood and Marrow Transplant Research registry study, the rates of fungal infections (FI) and the impact of FI on mortality after haploidentical (Haplo) or matched sibling (Sib) donor hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (Cy) were compared with Sib donor HCT using calcineurin inhibitor (CNI)-based GVHD prophylaxis.•Overall, rates of FI by day 180 post-HCT in HaploCy, SibCy, and SibCNI ranged from 1.9% to 5.2% for FI caused by yeast and from 1.7% to 3.7% for FI caused by mold.•Compared with SibCNI, rates of FI from yeast were higher for HaploCy but not for SibCy, and rates of FI from mold were higher in both HaploCy and SibCy.•In multivariable analyses, the presence of FI was associated with increased risk of mortality at 2 years post-HCT in all 3 cohorts. Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes. Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model. By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4