title: Secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Paediatric Haematology/Oncology, University Childrens Hospital Münster, Germany.
authors.forename: Katherine
authors.initials: K
authors.lastname: Allinson
authors.forename: Hedwig
authors.initials: H
authors.lastname: Kolve
authors.forename: Hans G
authors.initials: HG
authors.lastname: Gumbinger
authors.forename: H Josef
authors.initials: HJ
authors.lastname: Vormoor
authors.forename: Karoline
authors.initials: K
authors.lastname: Ehlert
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Groll
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000188:drug therapy / Q000382:microbiology / Q000601:surgery; D002648:Child; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000382:microbiology; D006801:Humans; D008297:Male; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D000935:Antifungal Agents