Liposomal amphotericin B followed by voriconazole for secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients

Abstract number: 1733_473

Allinson K., Kolve H., Gumbinger H.G., Vormoor H.J., Ehlert K., Groll A.H.

Objectives: Presumed or proven invasive pulmonary aspergillosis (IPA) is an important cause of infectious morbidity in patients with acute leukaemia. Although prior IPA is no longer a contraindication for subsequent allogeneic hematopoietic stem cell transplantation (HSCT), its successful management during granulocytopenia and immunosuppression remains challenging.

Methods: In the absence of an evidence-based approach, 11 adolescents (11 to 18 yrs) with acute leukaemia and a history of antecedent possible (4) or probable (7; modified EORTC/MSG criteria, Herbrecht et al. 02) IPA received liposomal amphotericin B (LAMB; 1 mg/kg QD) from the start of the conditioning regimen until engraftment and ability to take oral medication, followed by oral voriconazole (VCZ; 200 mg BID) until the end of the at-risk period. Nine patients had a good partial (>50% reduction in pulmonary infiltrates), and two a complete response to standard antifungal agents prior to admission for HSCT.

Results: Granulocyte engraftment occurred after a median of 16 days (r, 13–22). In addition to standard post transplant immunosuppression with methotrexate and cyclosporin A, 3 patients received short (<14), and 4 prolonged courses (r, 32–89 days) of methylprednisolon for acute grade I or II GVHD. The median duration of IV treatment with LAMB was 30 days (r, 19–36), followed by a median of 152 days (r, 19–210) of oral VCZ. LAMB was discontinued early in 1 patient and VCZ was transiently or permanently discontinued due to adverse events/new contraindications in 2 and 2 patients, respectively. At +180 days post transplant, 8 patients were alive, 6 with complete, and 1 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 (2) or refractory graft failure (1); while one of these patient had maintained a complete response, 2 died with secondary possible (1) or probable (1) IPA. Both patients had discontinued VCZ early and developed IPA in lung areas involved during the primary episode.

Conclusions: This paediatric series supports the notion that successful secondary antifungal prophylaxis for possible or probable IPA can be safely and effectively achieved in allogeneic HSCT. In the absence of chronic GVHD, reactivation or breakthrough infection appeared to be associated with recurrent leukaemia/graft failure and shorter duration of post-engraftment prophylaxis.