Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR(®) study

BACKGROUND: Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT), however, little is known about the impact of prior IFI on survival. METHODS: Patients with pre-transplant IFI (cases; n=825) were compared to controls (n=10,247). A subset analysis assessed outcomes in leukemia patients pre- and post-2001. RESULTS: Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of acute myeloid leukemia (AML), and having received cord blood, reduced intensity conditioning (RIC), mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior progression-free (PFS) and overall (OS) survival for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, p <0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13 vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared to later cases. CONCLUSIONS: Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates.