Bronchiolitis Obliterans Following Unrelated-Donor Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract 4504

Bronchiolitis obliterans (BO), occurring beyond 3 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been recognized as a late-onset noninfectious pulmonary complication associated with substantial morbidity and mortality. Some reports have described this complication with different incidence, associated risk factors, prognoses and therapeutic strategies. However, up to date, there is no unified understanding with respect to BO worldwide. In this study, we retrospectively analyzed the incidence, risk factors, clinical characteristics, management approaches and prognosis of BO among unrelated donor allo-HSCT recipients in our transplant center, aiming to improve cognition, reduce misdiagnose and dicrease motality in the future. Between June 2005 and May 2009, 117 patients underwent unrelated donor allo-HSCT while 98 patients who survived and were free of disease for more than 3 months after engraftment were enrolled. Myeloablative conditioning therapies for HLA-mathced transplant included busulfan-Cyclophosphamide (Bu-Cy) based regimens. In HLA-mismatched transplant, anti-thymocyte globulin (ATG) were added in addition to Bu-Cy based regimen. Patients were offered nonmyeloablative conditioning regimens when they were ineligible for myeloablative preparative regimens with fludarabine-based regimens including fludarabine, ATG and Bu. The diagnosis of BO was based on pulmonary function abnormalities, chest high-resolution CT (HRCT) findings and exclusion from respiratory infections. Management approaches for BO included immunosuppressive agents, azithromycin and symptomatic support. Some patients were further treated with etanercept (anti-tumour necrosis factor). In total 14 of the 98 patients (14.3%) developed BO at a median interval of 307.5 days post engraftment (range, 188–1316 days). Pulmonary function tests showed a decline in FEV1/FVC to a median interval of 0.51 (0.33-0.69) and FEV1 to 32% (17-46.2%) of predicted at BO diagnosis. Chest HRCT of BO patients showed areas of air trapping on expiratory views (71.4%), hyperinflation or bronchial dilatation (64.3%). All the 14 patients (100%) with BO complicated with chronic GVHD versus 41 of the 84 patients(48.6%) without BO (P<0.05). In total 1 of the 14 patients (7.1%) with BO underwent ATG-containing conditioning regimen versus 30 of 84 patients (35.7%) without BO (P<0.05). Multivariate analysis showed that primary disease type, donor and recipient's sex or age, stem cell type, myeloablative or nonmyeloablative conditioning regimen, aGVHD complication and HLA-disparities were not associated with the incidence of BO statistically. The prognoses of most BO patients were poor. In total only 4 of the 14 patients got improved and 3 were stable due to treatment while 2 were progressive and 5 (35.7%) died. Pulmonary failure was the leading cause of death for BO patients. In non-BO group, 23 of the 84 patients (28.6%) died, with a non-relapse mortality of 15.5% and infection became the leading cause of death. The non-relapse mortality in BO patients was higher than that in non-BO patients although there was no statistical significance (P>0.05). In all, our results demonstrated that chronic GVHD and conditioning regimen containing ATG, but not others which had been reported to be related with BO, were two risk factors associated with BO and the prognosis was extremely poor. More clinical trials and basic researches should be carried out to allow prospective identification of patients at greatest risk and early new therapeutic intervention to finally improve the survival of patients in this group.