title: Factors associated with bronchiolitis obliterans syndrome and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation.
abstract: Bronchiolitis obliterans syndrome (BOS) is a form of chronic graft vs. host disease (cGVHD) and a highly morbid pulmonary complication after allogeneic hematopoietic stem cell transplantation (HSCT). We assessed the prevalence and risk factors for BOS and cGVHD in a cohort of HSCT recipients, including those who received reduced intensity conditioning (RIC) HSCT. Between January 1, 2000 and June 30, 2010, all patients who underwent allogeneic HSCT at our institution (n = 1854) were retrospectively screened for the development of BOS by PFT criteria. We matched the BOS cases with two groups of control patients: (1) patients who had concurrent cGVHD without BOS and (2) those who developed neither cGVHD nor BOS. Comparisons between BOS patients and controls were conducted using t-test or Fisher's exact tests. Multivariate regression analysis was performed to examine factors associated with BOS diagnosis. All statistical analyses were performed using SAS 9.2. We identified 89 patients (4.8%) meeting diagnostic criteria for BOS at a median time of 491 days (range: 48-2067) after HSCT. Eighty-six (97%) of our BOS cohort had extra-pulmonary cGVHD. In multivariate analysis compared to patients without cGVHD, patients who received busulfan-based conditioning, had unrelated donors, and had female donors were significantly more likely to develop BOS, while ATG administration was associated with a lower risk of BOS. Our novel results suggest that busulfan conditioning, even in RIC transplantation, could be an important risk factor for BOS and cGVHD.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Lee
authors.initials: L
authors.lastname: Gazourian
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Rogers
authors.forename: Ruby
authors.initials: R
authors.lastname: Ibanga
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Weinhouse
authors.forename: Victor
authors.initials: V
authors.lastname: Pinto-Plata
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Baron
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
mesh_terms: D000328:Adult; D064591:Allografts; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001989:Bronchiolitis Obliterans / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D002066:Busulfan / Q000009:adverse effects*; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D005541:Forced Expiratory Volume; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011183:Postoperative Complications / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D013601:T-Lymphocytes; D019172:Transplantation Conditioning / Q000009:adverse effects*; D061349:Unrelated Donors; D014797:Vital Capacity
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D002066:Busulfan