Impact of Prior Invasive Pulmonary Aspergillosis (IPA) on Outcome in Patients Receiving Reduced Intensity Conditioning (RIC) Allogeneic Haematopoietic Stem Cell Transplantation (Allo-SCT).

Invasive Pulmonary Aspergillosis (IPA) is a major cause of morbidity in patients with hematological malignancies. The aim of this single centre retrospective study was to determine the impact of prior IPA on outcome after RIC Allo-SCT. All cases of proven or probable IPA diagnosed prior to performance of RIC Allo-SCT at the Paoli-Calmettes Institute Cancer Centre from 1 January 2000 through 31 December 2007 were included. 28 patients were identified among 434 patients undergoing Allo-SCT. Patients’ data were collected from a maintained database and by retrospective clinical chart review. Twenty eight cases were identified. Gender: M/F (16/12); median age at diagnosis was 53 years (18–65). 23 patients (82%) had acute myeloid leukemia. In all patients, IPA was diagnosed according to standard procedures. IPA therapy included: 20 patients (71%) were receiving Voriconazole; 4 patients Itraconazole, and 4 patients with an association of different antifungal drugs including Caspofungine, Liposomal Amphoteracine-B, or Posaconazole. The median duration of treatment prior to RIC was 8 months range (1–16). The median time between the diagnosis of IPA and transplantation was 6 months (1–27); 20 patients (71%) received a graft from a family donor, 4 patients had a MUD, and 4 patients received cord blood cells donors. 21 patients (75%) received a conditioning regimen with Fludarabine Busulfan and ATG, and 4 patient (14%) received a conditioning with Fludarabine Cyclophosphamide and TBI, 3 patients (11%) Fludarabine and TBI, Most patients (n=25; 89%) received or continued a secondary prophylaxis against aspergillosis at time of Allo-SCT: 17 (68%) had a prophylaxis with Voriconazole; 3 patients Itraconazole, 2 patients Posaconazole. After RIC transplantation only 4 patients (14%) had reactivation of their IPA. The latter 4 patients were experiencing severe acute GVHD treated with high dose corticosteroids. None of these patients died of IPA. Actually 18 patients (64%) are still alive with a median follow up of 23.5 months (12.6–48.5). Overall survival at 2 years was 59% [95%CI, 43–83]. In all, 3 patients died from other causes not directly related to IPA, 2 patients because of relapse or disease progression, and one due extensive chronic GVHD. In comparison to literature in standard myéloablative allo-SCT setting, these data suggest that adequately treated and controlled IPA prior to RIC Allo-SCT do not worsen outcome. The latter is likely due to multiple changes in transplantation practice, including the RIC nature of the conditioning regimens, the infusion of peripheral blood stem cells, rapid diagnosis of IPA, and use of modern efficient antifungal drugs.