Secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients

Objectives: Presumed or proven invasive pulmonary aspergillosis (IPA) is an important cause of infectious morbidity in patients with acute leukaemia. Although prior IPA is not a contraindication for subsequent allogeneic haematopoietic stem cell transplantation (HSCT), its management during granulocytopenia and immunosuppression remains challenging. Patients and methods: In the absence of an evidence-based approach, 11 adolescents (11-18 years) with acute leukaemia and a history of antecedent possible (4) or probable (7) IPA received liposomal amphotericin B (LAMB; 1 mg/kg once a day) from the start of the conditioning regimen until engraftment and ability to take oral medication, followed by oral voriconazole (200 mg twice a day) until the end of the at-risk period. Nine patients had a good partial response (> 50% reduction in pulmonary infiltrates) and two had a complete response prior to HSCT. Results: The median duration of intravenous treatment with LAMB was 30 days (range, 19-36), followed by a median of 152 days (range, 19-210) of oral voriconazole. LAMB was discontinued early in one patient and voriconazole was transiently or permanently discontinued due to adverse events/new contraindications in two and two patients, respectively. At +180 days post-transplant, eight patients were alive, six with complete, and one each with near complete and ongoing resolution of pulmonary infiltrates; all but one were in continuing haematological remission. Three patients had succumbed either to recurrent leukaemia (two) or refractory graft failure (one); whereas one of these patients had maintained a complete response, two died with secondary possible (one) or probable (one) IPA. Both patients had discontinued voriconazole early and developed IPA in lung areas involved during the primary episode. Conclusions: This prospective paediatric series supports the notion that secondary antifungal prophylaxis for possible or probable IPA can be safely achieved in allogeneic HSCT. In the absence of chronic graft-versus-host disease, breakthrough infection appeared to be associated with recurrent leukaemia/graft failure and shorter duration of post-engraftment prophylaxis.