JAC Advance Access published online on January 31, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm521
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Original research |
Secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients
1 Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Paediatric Haematology/Oncology, University Childrens Hospital Münster, Germany 2 Cardiff University School of Medicine, Cardiff, Wales, UK 3 Pharmacy Department, University Hospital Münster, Germany 4 Department of Pharmacology and Toxicology, University Hospital Münster, Germany
Received 9 July 2007; returned 25 September 2007; revised 3 November 2007; accepted 9 December 2007
* Correspondence address. Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Paediatric Haematology/Oncology, Children's University Hospital, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany. Tel: +49-251-835-2801; Fax: +49-251-835-2804; E-mail: grollan{at}ukmuenster.de
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.
Key Words: mycoses , stem cell transplantation , voriconazole , amphotericin B