Caspofungin as primary antifungal prophylaxis in stem cell transplant recipients

Objectives. To assess the effectiveness and tolerability of caspofungin as primary prophylaxis against invasive fungal infections in stem cell transplant recipients who are poor candidates for triazole or lipid amphotericin B prophylaxis due to renal or hepatic dysfunction, and to determine whether any patient characteristics are independently associated with an increased risk of breakthrough invasive fungal infection during caspofungin prophylaxis. Design. Retrospective medical record review. Setting. Tertiary care comprehensive cancer center. Patients. One hundred twenty-three adult stem cell transplant recipients who received caspofungin 35-50 mg/day for up to 100 days after transplantation as primary antifungal prophylaxis between January 1, 2002, and June 30, 2005. Measurements and Main Results. Data were collected on host and transplant characteristics such as transplant type, neutropenia, graft-versus-host disease (GVHD), and corticosteroid use, as well as evidence of breakthrough invasive fungal infections. Of the 123 patients, 117 (95.1%) were allogeneic recipients, and the median time to engraftment was 12 days (range 6-26 days). Fifty (40.7%) of the patients developed GVHD of grade 2 or greater and received corticosteroids for more than 21 days. Median duration of caspofungin prophylaxis was 73 days (range 10-100 days). Nine patients (7.3%) developed breakthrough invasive fungal infections (two cases of mixed Aspergillus species and one each of Aspergillus terreus, Rhizopus, Exserohilum, an unspecified mold, Cryptococcus, Candida glabrata, and Candida tropicalis). Median time to invasive fungal infection development was 65 days (range 12-88 days). Only one case occurred during the neutropenic period before engraftment. Multivariate analysis showed that Pseudomonas coinfection (p=0.04) and infliximab therapy (p=0.02) were associated with breakthrough invasive fungal infections in patients receiving caspofungin. By day 100, there were five (4.1%) deaths, two of which were directly attributable to invasive fungal infections. No caspofungin-related adverse events were reported. Conclusion. Caspofungin seems to be an effective and well-tolerated option for primary antifungal prophylaxis in the highly immunosuppressed stem cell transplant patient population.