Risk factors for bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplantation

Abstract

Background The occurrence of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after allo-HSCT. Methods A nested case-control study was designed. Cases with BOS and controls matched for the year of allo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent allo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia. Results Thirty-six patients suffered from BOS; the mean age at the time of presentation was (32.7±12.4) years, and the mean time to presentation was (474±350) days post-HSCT. A pre-HSCT cyclophosphamide dose of ≥3.2 g/m2 (OR=8.74, P=0.025), chronic graft-versus-host disease (moderate to severe) (OR=12.02, P=0.000), and conditioning regimens without antithymocyte globulin (OR=2.79, P=0.031) were independently associated with BOS. Conclusions We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after allo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.