title: Identification of risk factors for bronchiolitis obliterans syndrome after reduced toxicity conditioning before hematopoietic cell transplantation.
abstract: Allogeneic hematopoietic cell transplantation (allo-HCT) of older or patients with comorbidities has become possible due to new regimens for reduced-intensity conditioning. The use of fludarabine, carmustine and melphalan as the preparative regimen (FBM) reduces toxicity while providing substantial anti-leukemic activity. Chronic GVHD (cGVHD) of the lung or bronchiolitis obliterans syndrome (BOS) remains a serious non-infectious complication contributing to treatment-related morbidity. We conducted a retrospective analysis of 259 patients (median age: 61.5, range: 24-76 years) transplanted after FBM conditioning to identify and characterize clinical risk factors for developing BOS. The cumulative incidence rate of BOS was 4.2% (95% confidence interval (CI): 2.4-7.6%) at 1 year and 8.5% (95% CI: 5.6-12.9%) at 5 years after allo-HCT with a median follow-up of 36.5 (range: 3-136) months. In multivariate analysis, age <55 years at allo-HCT (who received 25% higher carmustin-dose in preparative regimen), pulmonary complications after allo-HCT and GVHD prophylaxis without in-vivo T-cell depletion (cyclosporine-A/ATG or cyclosporine-A/alemtuzumab) were associated with BOS. We observed no significant differences in clinical variables such as smoking or lung diseases before allo-HCT. In contrast to cGVHD affecting other organs, BOS showed no impact on overall survival. In conclusion, we identified risk factors associated with developing BOS after conditioning with a reduced toxicity protocol.
authors: Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany.
authors: J
authors: J
authors: Duque-Afonso
authors: G
authors: G
authors: Ihorst
authors: R
authors: R
authors: Wäsch
authors: H
authors: H
authors: Bertz
authors: J
authors: J
authors: Müller-Quernheim
authors: J
authors: J
authors: Finke
authors: A
authors: A
authors: Prasse
authors: R
authors: R
authors: Marks
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001989:Bronchiolitis Obliterans / Q000188:drug therapy / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult