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Allogeneic Hematopoietic Stem Cell Transplantation in Patients with a History of Prior Invasive Aspergillosis Outcomes and Risks for Post-Transplant Invasive Aspergillosis



Allogeneic Hematopoietic Stem Cell Transplantation in Patients with a History of Prior Invasive Aspergillosis Outcomes and Risks for Post-Transplant Invasive Aspergillosis



Blood 100(11): Abstract No. 2463



Background: Patients with a history of invasive aspergillosis (IA) prior to transplant may be at high risk for IA recurrence and transplant-related mortality (TRM) after hematopoietic stem cell transplantation (HCT). This study was performed to determine outcomes and to identify risk factors for recurrent IA and TRM in allogeneic HCT patients with a history of prior IA. Methods: Between 12/1992 and 5/2001, we performed prospective monitoring to identify patients with a history of IA prior to first allogeneic HCT at FHCRC. Patients with IA that was defined as possible, probable, or proven according to established EORTC/NIH-MSG criteria were included. Practice was to treat patients with IA for at least one month prior to HCT; stabilization of radiographic signs was required to proceed with transplant. Post-transplant outcomes (IA and TRM) were determined by chart review and compared to contemporaneous controls. Log-rank tests were used to compare the probabilities of IA after transplant over time across patient subgroups. Results: Among 2319 patients who underwent first allogeneic HCT, 44 patients (1.9%; 36 myeloablative, 8 nonmyeloablative) were known to have prior IA (34 proven, 2 probable, 8 possible). Median time from diagnosis of IA to transplant was 100 days (range; 7-2422). Thirteen patients (30%) were diagnosed with IA at a median of 27 days (range; 1-242) after transplant. Receipt of antifungal therapy for <30 days before transplant (usually due to rapidly progressive underlying disease) was associated with higher risks of IA after transplant and TRM within 100 days (4/6 vs. 6/38, p=0.001 and 4/6 vs. 13/38, p=0.03, respectively). Resolution of chest radiographic abnormality by the time of HCT was associated with a decreased risk of IA recurrence (p=0.03). Unrelated donor HCT and positive donor or recipient CMV serostatus were additional risks for IA recurrence within 1 year (p=0.04 and p=0.01, respectively). Patients who received nonmyeloablative compared to TBI-containing myeloablative conditioning (n=30) showed a trend towards low 1-year IA recurrence (1/8 vs. 11/30, n.s.). TBI-containing myeloablative conditioning was associated with a higher 1-year TRM when compared to nonmyeloablative or non-TBI-containing myeloablative conditioning regimens (p=0.02). Overall survival was significantly lower in the 44 patients with a history of IA compared to the 2275 contemporaneous controls (36% vs. 58% at 1-year, p=0.0001). Post-transplant IA contributed to the deaths of 11 patients (25%); an additional 10 patients died due to pulmonary complications including idiopathic pneumonia syndrome (n=5) and non-Aspergillus infectious pneumonia (n=5). Conclusion: Patients with a history of IA have a high risk for transplant-related mortality, associated mainly with IA recurrence and pulmonary-related deaths. IA recurrence may be minimized by prolonged (>30 days) and more aggressive antifungal therapy prior to HCT, with resolution of radiographic abnormalities, and, possibly, HCT with nonmyeloablative or non-TBI-containing myeloablative conditioning regimens.

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