HCT May Still Be Successful in Patients With Uncontrolled IFI Prior to Transplant

The results of a recent study suggest that hematopoietic cell transplantation (HCT) in patients with invasive fungal infection (IFI) before transplant, without regression or stabilization of radiographic signs, may be successful despite mixed radiographic response of IFI. The study was presented at the 2018 BMT Tandem Meetings in Salt Lake City, Utah.

Patients who undergo HCT for hematologic malignancy or bone marrow failure “often have prolonged neutropenia prior to transplant and can develop IFI,” according to the authors of the study. Therefore, it is recommended to control underlying IFI prior to transplant, indicated by regression or stabilization of radiographic findings. “When serial imaging is an important indicator of treatment success, a radiographic ‘mixed response’ (some lesions regressing or stable, others increasing in size or number) poses a serious clinical dilemma,” the authors write. However, sometimes control of IFI might not be attainable and transplant must continue as it is the only chance for neutrophil recovery.

For the study, the investigators analyzed the medical records of 97 HCT recipients “who underwent pretransplant infectious disease consultation from 2009 to 2017.” Of these 97 patients, 10 still underwent HCT, despite having “incomplete radiographic control of a known or suspected fungal infection,” according to the authors. The investigators then recorded post-HCT outcomes of new or worsening IFI, changes in antifungal therapy, or death.

A total of 5 of the 10 patients had pulmonary aspergillosis (1 had a coccidioidomycosis co-infection); 2 had hepatosplenic candidiasis (1 had an aspergillus co-infection); 2 had pulmonary nodules of unknown etiology, and 1 had pulmonary mucormycosis.

All of the patients had received a median of 89 days of antifungal therapy (range of 14 to 246 days) prior to HCT. Half of the patients underwent HCT because of prolonged neutropenia (median of 95 days; range of 71 to 199 days) and the lack of other options.

The investigators also shared that 5 of the patients were not neutropenic; however, the study team felt that they had the “best achievable antifungal response.” Furthermore, “1 patient had worsening IFI by imaging prior to engraftment and improved with a change in antifungal therapy.”

Post-engraftment, 1 was shown to have nodules that had increased in size. This patient subsequently died of IFI 126 days post HCT after first seeing improvement and discontinuation of voriconazole. A total of 2 other patients died of underlying disease relapse and 2 others died of graft versus host disease without IFI. Those 2 patients had a median survival time of 126 days (range 106 to 2802 days).

Among the 5 patients who survived, 2 are currently on posaconazole for mucormycosis or prophylaxis, and 3 have completed therapy for IFI.

Based on the results of this small study, HCT may still be successful in cases with incomplete radiographic control of IFI prior to transplant.