Efficacy of Fluconazole Prophylaxis for Autologous Peripheral Blood Stem Cell Transplantation: Results of a Prospective, Randomized, Controlled, Multicenter, Open Label Study.

Infection is the leading cause of morbidity and mortality among hematopoietic stem cell transplant (HSCT) recipients. Fungal infection is particularly a threat because of difficulty in both diagnosis and treatment. The frequency of fungal infection is largely dependent on the mode of transplantation and duration of neutropenia. While fluconazole prophylaxis in allogeneic and autologous BMT is well studied, a trial in autologous PBSCT is lacking.

Methods: The Texas Stem Cell Transplant Consortium initiated a phase III randomized study to evaluate the efficacy of fluconazole for prophylaxis of invasive fungal infections (IFI) following autologous PBSCT with an initial planned enrollment of 150 patients. Patients were randomized to receive either no prophylaxis or fluconazole 400mg/day (or 12mg/kg if <18 years of age) beginning on the day of stem cell re-infusion. The prophylaxis phase continued until the post-nadir absolute neutrophil count (ANC) reached 1000/μL or until the patient developed an IFI according to criteria developed by the IFI Cooperative Group of the EORTC. Primary endpoints measured included the comparative incidence of proven, probable or possible IFI through engraftment and through day 100 post-transplantation and IFI-related mortality through day 100. Overall survival and the comparative incidence of superficial fungal infection were also analyzed.

Results: Thirty patients have been enrolled to date (16 fluconazole, 14 without prophylaxis). The median stem cell dose received was 3.5 million CD34+ cells/kg for patients randomized to fluconazole versus 6.2 million CD34+ cells/kg for those that did not receive antifungal prophylaxis. The median duration of neutropenia, defined as an ANC <1000/μL, was 7.5 days versus 7 days with a median duration of fever ≥100.5°F of 2 days and 2.5 days respectively. Superficial fungal infection developed in none of the patients that received fluconazole versus 31.3% of patients that did not receive antifungal prophylaxis. Additionally, the incidence of proven IFI was 0% in the fluconazole group versus 18.8% in those that did not receive prophylaxis and mortality due to proven IFI was 0% and 16.7% respectively. Although the small numbers do not allow for statistical comparison, the study was terminated early as a result of the high incidence of IFI and IFI-related mortality in the patients randomized to receive no anti-fungal prophylaxis.

Conclusion: Results of this study suggest that fluconazole prophylaxis should be provided as standard of care in patients following autologous PBSCT.