Reported risk factors for bronchiolitis obliterans (BO) in allogeneic bone marrow transplant recipients come from studies of modest size and are limited to the experiences of single institutions. Using registry data from the International Bone Marrow Transplant Registry, we sought to identify risk factors for BO in a large cohort of patients transplanted in multiple institutions.
Data on a cohort of 6,275 adult patients with leukemia who received HLA–matched sibling transplants from 1989–97 and survived at least 100 days posttransplant were evaluated for the study. The association of pre- and posttransplant factors with the occurrence of BO was analyzed using proportional hazards regression.
Seventy-six patients were found to have BO. The incidence rate of BO was 1.7% at 2 years posttransplant. The Kaplan-Meier estimate of median time to onset of BO was 431 days. Histologic evaluation of BO was performed in 36 patients (47%). In 28 patients (37%) diagnosis was based on pulmonary function tests, CT scan of the chest, or a combination of both.CONCLUSIONS: We found BO to be an infrequent complication of allogeneic bone marrow transplantation for leukemia in adults. Several pre-transplant and post-transplant factors were associated with an increased risk for BO.
In contrast to the preponderance of GVHD as risk factor for BO in previous studies, these findings suggest that a variety of mechanisms (immune-mediated and treatment-related toxicity) alone or in combination, may be responsible for the pathogenesis of BO.
Factors associated with the risk of developing BO*Risk FactorHazard Ratio95% CIp† ValuePretransplantBusulfan-based conditioning regimen (vs. TBI-based)1.971.20 – 3.240.0069Diagnosis to transplant ≥ 14 months1.661.01 – 2.750.0464Female donor → male recipient sex match2.041.26 – 3.310.0039CML (vs. other leukemia)1.691.02 – 2.810.0424PosttransplantAcute GVHD (grade II, III or IV)2.111.30 – 3.430.0025Interstitial pneumonitis2.551.47 – 4.420.0009*
CI denotes confidence interval; TBI = total body irradiation; GVHD = graft versus host disease.†
p Values are based on the Wald test.
L.H. Santo Tomas, None.