Efficacy and Safety of Micafungin for the Prophylaxis of Invasive Fungal Disease During Neutropenia in Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

The use of micafungin, a member of the novel class of antifungal agents, the echinocandins, in adults has proven to be effective and safe for antifungal prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. However, there are few reports describing its prophylactic use in pediatric patients. The objectives of this study were to evaluate the efficacy and safety of micafungin for the prevention of invasive fungal disease (IFD) in patients undergoing allogeneic HSCT exclusively focusing on children and adolescents.

This was prospective, multi-center, open-label, single arm study. The study drug, micafungin, was administered intravenously at a dose of 1 mg/kg/day for patients < 50 kg and 50 mg/day for patients ≥50 kg from the beginning of conditioning until neutrophil engraftment. Treatment success was defined as the absence of suspected, probable, or proven IFD through the end of 4 weeks after therapy. Clinical and laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0.

From April 2010 to December 2011, 152 patients were enrolled from 10 institutions in Korea, and a total of 144 patients were analyzed. The median age of the patients was 9.5 years (range, 0.4 – 19.8 years). Approximately 94% of patients received myeloablative conditioning regimen. Graft source included bone marrow (11.9%), peripheral blood (82.5%) and cord blood (5.6%). Most commonly, patients received HSCT for treatment of acute myeloid leukemia (27.8%), acute lymphocytic leukemia (27.1%), or severe aplastic anemia (19.4%). The median duration of prophylactic micafungin treatment was 23 days (range, 4 –169 days). Of the 144 patients, 117 patients completed micafungin prophylactic administration until neutrophil engraftment. Eleven patients developed suspected (n=5), possible (n=3), or probable (n=3) IFD. No patients died of IFD at any time during the study. Thirty-eight patients experienced adverse events (AEs) possibly related to micafungin. Only two patients discontinued micafungin prophylaxis due to AEs. Common AEs included hepatotoxicity, gastrointestinal discomfort, electrolyte imbalance and myelosuppression.

This study shows the efficacy and safety of micafungin for the prevention of IFD after allogeneic HSCT in children and adolescents.

No relevant conflicts of interest to declare.