Mold Invasive Fungal Infection in Hematopoietic Cell Transplant With Post-Transplant Cyclophosphamide and Posaconazole Prophylaxis

Abstract

Post-transplantation cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis regimens may increase the incidence of mold invasive fungal infections (IFI). Nevertheless, data on prophylaxis strategies and donor modalities are heterogeneous, and reports on posaconazole prophylaxis remain limited. The objectives were to characterize mold IFI incidence, risk factors, and impact on outcomes in patients with hematologic malignancies undergoing PTCy-based HCT from matched sibling, matched unrelated, and haploidentical donors under posaconazole prophylaxis. This is a single-center retrospective study of mold IFI episodes in 435 patients undergoing HCT at a single institution. Daily 300 mg posaconazole dosage was given between days +7 and +90 or during GVHD on steroids. Mold IFI affected 6% of patients (16 possible, 8 probable, and 2 proven), with 73% of breakthrough infections. Only Aspergillus spp. was identified. With a median onset of 88 days, the 2-yr cumulative incidence was 5.6% overall and 2.1% for probable/proven mold IFI. Grade II-IV acute GVHD and a higher HCT comorbidity index increased the risk for probable/proven mold IFI. One patient died from mold IFI, although 7% of deaths occurred with active mold IFI. Probable/proven mold IFI negatively impacts on overall survival (OS). Mold IFI is an infrequent complication in allogeneic HCT with PTCy under posaconazole prophylaxis, although acute GVHD significantly increases its risk. While direct mortality is low, OS is negatively impacted by probable/proven mold IFI.

Keywords: Invasive fungal infection; Molds; Posaconazole; Post-transplant cyclophosphamide; Sirolimus.