Outcomes of Hematopoietic Cell Transplantation in Patients with Mixed Response to Pretransplantation Treatment of Confirmed or Suspected Invasive Fungal Infection

•Mixed response invasive fungal infection (IFI) before hematopoietic cell transplantation (HCT) often does not reflect uncontrolled infection.•With appropriate therapy, most mixed response IFI will not worsen pre-engraftment.•In this series, no post-transplantation mortality was related to IFI diagnosed before HCT. Patients with hematologic malignancy or bone marrow failure are typically required to achieve radiographic improvement or stabilization of invasive fungal infection (IFI) before hematopoietic cell transplantation (HCT) owing to a concern for progression before engraftment. Refractory IFI with a mixture of improvement and progression on serial imaging (ie, mixed response) poses a clinical dilemma, because a delay in HCT may allow for a hematologic relapse or other complications. Furthermore, HCT itself may yield the immune reconstitution necessary for clearance of infection. We sought to describe the characteristics and outcomes of patients who underwent HCT with mixed response IFI. We performed a chart review of all patients who underwent HCT between 2014 and 2020 in whom imaging within 6 weeks before HCT indicated a mixed response to treatment of a diagnosed IFI. Fourteen patients had evidence of a mixed response in low-to-moderate burden of diagnosed IFI by imaging before HCT, including 9 with pulmonary aspergillosis, 2 with hepatosplenic candidiasis (1 also with aspergillosis), and 4 with pulmonary nodules of presumed fungal etiology. Five had refractory severe neutropenia at evaluation for HCT (median, 95 days). All 14 patients showed radiographic stability or improvement in imaging following engraftment; no IFI-related surgeries were required, and no IFI-related deaths occurred. For patients without relapse who underwent HCT more than 1 year earlier, 7 of 8 (88%) were alive at 1 year. Our findings suggest that low-to-moderate burden IFI with mixed response is unlikely to progress on appropriate therapy before engraftment during allogeneic HCT.