Presumptive treatment strategy for aspergillosis in allogeneic haematopoietic stem cell transplant recipients

Abstract

The onset of invasive aspergillosis (IA) after allogeneic haematopoietic stem cell transplantation (HSCT) is bimodal. However, IA early after HSCT has become less frequent due to the shortened neutropenic period, and the clinical significance of empirical treatment for aspergillosis based on persistent febrile neutropenia (FN) became less clear. Therefore, we started a presumptive treatment strategy, in which anti-Aspergillus agents were started when patients developed positive serum test and/or infiltrates or nodules on X-ray or CT-scan associated with persistent FN, in 2002. We retrospectively reviewed the records of 114 adult patients who underwent allogeneic HSCT between September 2002 and December 2005 in high-efficiency particulate air-filtered clean rooms. Fluconazole was given as anti-Candida prophylaxis. The primary endpoint was the development of early IA, which was defined as probable or proven IA according to the EORTC/MSG criteria that developed between the day of HSCT and 7 days after engraftment. Among 73 patients who experienced persistent FN for 7 days or longer, anti-Aspergillus agents were empirically started in 13 patients at the discretion of attending physicians, whereas 60 patients actually followed presumptive treatment strategy. Only 4 of 60 patients received anti-Aspergillus agents. Two patients in the presumptive group developed early IA, but were successfully treated with anti-Aspergillus agents started after the diagnosis of IA. These findings suggested the feasibility of a presumptive treatment strategy for aspergillosis in HSCT recipients. A randomized controlled trial is warranted to compare empirical and presumptive anti-Aspergillus strategy in allogeneic HSCT recipients.