Secondary Antifungal Prophylaxis in Allogeneic Hematopoietic Stem Cell Recipients

Invasive fungal infection (IFI) is a serious complication in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is widely accepted that the patients with stable fungal infection is not a contraindication for allo-HSCT, but whether transplantation can be done in the patients with active fungal infections is still a matter of discussion. In addition, the optimal agent for SAP is not well defined. In this study, we investigated the efficacy of SPA for recipients in stable state or active state of prior invasive pulmonary aspergillosis (IPA). The choice of prophylaxis agent was based on treatment response of initial antifungal therapy.

A total of 63 patients with prior IPA undergoing allo-HSCT were enrolled in this prospective study. Forty-one patients with IPA were in stable and 22 patients were in active state at the time of transplant. SAP was given from the start of the conditioning until 90 days after transplantation for patients in stable state or until eradication of residual foci for patients in active state. The same agent was given for SAP if patients developed acute GVHD and treated with corticosteroids. The agents of SAP included Itraconazole in 16, Vorinazole in 30, Caspofungin in 12 and Amphotericin B in 5 cases. In addition, surgery was performed in 3 patients who had the cavity lesion of more than 2cm diameter in lung before HSCT.

The median time of SAP was 96 days (range, 13 to 183). None of the patients was interrupted prophylaxis due to event of intolerance. At a median follow-up period of 260 days (range, 13–2010), 22 patients (34.9%) occurred the relapse of IPA, including 11 (17.5%) occurred SAP failure. Two-year cumulative incidence of IPA relapse was 42.8%±7.3%. The incidence of SAP failure was similar between the patients with active IPA and stable IPA (26.9% vs. 12.4%; P=0.174). The rates of SAP failure were not different between the different antifungal agents. Multivariate analyses showed II to IV aGVHD was the risk factor of SAP failure (RR= 14.4, 95%CI 3.011–68.864, P=0.001). None of the 3 patients underwent surgery occurred IPA relapse. And 3 patients with the cavity lesion of more than 2cm diameter in lung not received surgery all occurred IPA after HSCT including one died of hemoptysis. All the patients occurred IPA relapse received the salvage therapy for IFI. Seven patients achieved CR, 11 achieved PR and 4 patients had no response to the treatment. Six patients occurred IFI-related mortality including 3 cases in active state and 3 in stable state. At the end of follow-up, 26 patients were alive, 20 patients die of leukemia relapse and 17 died of transplant-related mortality. Five-year overall survival (OS) and disease-free survival (DFS) were 38.0% and 34.0%, respectively. OS and DFS were similar between active patients and stable patients.

The results suggest that active fungal infection is not a contraindication for allo-HSCT. It appears to be safe and effective to choose the antifungal agent for second prophylaxis based on treatment response of initial antifungal therapy.

No relevant conflicts of interest to declare.