Invasive Pulmonary Aspergillosis Is Not a Contraindication to Reduced-Intensity Conditioned Allogeneic Haematopoietic Stem Cell Transplantation (RIC allo-HSCT).

Ten patients with focal abnormalities on CT prior to RIC allo-ASCT, in whom follow-up CT studies were available, were studied. All 10 had received prior chemotherapy for AML/MDS and had received treatment for high probability invasive pulmonary aspergillosis (IPA). The RIC protocol comprised “FBC”- fludarabine 30 mg/m² intravenously from Day -9 to Day -5; busulphan 4mg/kg/day orally from Day -3 to Day -2 and alemtuzumab (CAMPATH-1H) 20mg intravenously from Day -8 to Day -4. Unselected peripheral blood stem cells (PBSCs) or bone marrow (BM) was infused on Day 0. Immunosuppression was achieved with cyclosporine 1.5 mg/kg intravenously 12 hourly from Day -1. Neoral^â was substituted when a good oral intake was tolerated and tapered from Day +56 in the absence of GvHD. Filgrastim 300 mcg iv/sc was administered from Day +7 to neutrophil engraftment (neutrophils ≥ 0.5x10⁹/l). All patients received standard nursing and supportive care protocols for neutropenic patients. In addition these patients received Ambisome 3mg/kg intravenously daily until full neutrophil regeneration had occurred, then prophylactic Ambisome (2mg/kg thrice a week) till immunosuppression was stopped. Two thoracic radiologists (blinded to the timing of examinations) independently reviewed the CT studies pre- and post-RIC allo-HSCT. The site and size of individual lesions was evaluated. The likelihood (recorded as probable, possible, indeterminate or unlikely; denoting probabilites of ≥75%, ≥50%, ≥25% and <25% [respectively]), that individual lesions represented foci of angioinvasive fungal infection was noted. Serial changes in size, the appearance of new lesions (if any), and an overall impression of change in each patient (somewhat better or worse, significantly better or worse, no change) at follow-up CT, were also recorded. There were 48 lesions (probable, n=16; possible, n=18; indeterminate, n=13 and unlikely, n=1) on CT prior to RIC allo-HSCT. At follow-up CT, 12/16 (75%) probable and 10/18 (56%) possible lesions had either regressed or were smaller than prior to RIC allo-HSCT. Only 1/18 (6%) lesions graded as possible had increased in size following RIC allo-HSCT. Five new lesions (probable, n=2; possible, n=2; indeterminate, n=1) were demonstrated in five patients. The overall impression on follow-up was that CT studies were somewhat better (n=3) or significantly better (n=6) in 9/10 (90%) patients. In patients with pre-existing lesions on CT prior to RIC allo-HSCT, there was no evidence of progression in the majority of patients, and no patient died of IPA in the follow-up period. Documented IPA may not be a contraindication to RIC allo-HSCT in patients with haematological malignancy, which can be safely performed with our conditioning and supportive care protocol.