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Post-Transplant Events

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.

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Acknowledgements

This study was supported by the German Federal Ministry of Education and Research (BMBF 01 EO 0803). We thank Irmgard Matt for managing the data bank of transplanted patients, Carole Cürten for proofreading assistance, the medical technicians in the Stem Cell Transplantation Unit and Pulmonary Function Test Unit of the University Medical Center Freiburg, and all the patients and staff on the Löhr ward. We thank also Elisabeth Lenartz for transplantation coordination and Roland Mertelsmann for continuous support.

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Correspondence to R Marks.

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Duque-Afonso, J., Ihorst, G., Wäsch, R. et al. Identification of risk factors for bronchiolitis obliterans syndrome after reduced toxicity conditioning before hematopoietic cell transplantation. Bone Marrow Transplant 48, 1098–1103 (2013). https://doi.org/10.1038/bmt.2013.3

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