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(Chest. 2005;128:153-161.)
© 2005 American College of Chest Physicians

Risk Factors for Bronchiolitis Obliterans in Allogeneic Hematopoietic Stem-Cell Transplantation for Leukemia*

Linus H. Santo Tomas, MD, MS; Fausto R. Loberiza, Jr, MD, MS; John P. Klein, PhD; Peter M. Layde, MD, MS; Randolph J. Lipchik, MD; J. Douglas Rizzo, MD; Christopher N. Bredeson, MD, MS and Mary M. Horowitz, MD, MS

* From the Division of Pulmonary and Critical Care Medicine (Drs. Santo Tomas and Lipchik), Department of Medicine; Division of Epidemiology (Dr. Layde), Health Policy Institute; and International Bone Marrow Transplant Registry (Drs. Loberiza, Klein, Rizzo, Bredeson, and Horowitz), Medical College of Wisconsin, Milwaukee, WI.

Correspondence to: Linus H. Santo Tomas, MD, MS, Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, 9200 West Wisconsin Ave, Milwaukee, WI 53226; e-mail: santo{at}mcw.edu

Study objectives: Reported risk factors for bronchiolitis obliterans (BO) in allogeneic hematopoietic stem-cell transplant recipients come from modest-sized studies and are limited to experiences of single institutions. We sought to identify risk factors for BO using data from the International Bone Marrow Transplant Registry.

Methods: Registry data on 6,275 adult patients with leukemia who received human leukocyte antigen-identical sibling transplants from 1989 to 1997 and survived at least 100 days after transplantation were evaluated for the study. Risk factors for BO were analyzed using proportional hazards regression.

Results: Seventy-six patients were found to have BO, with an incidence rate of 1.7% at 2 years after transplantation. The Kaplan-Meier estimate of median time to onset of BO was 431 days. Histologic evaluation was performed in 36 patients (47%). In 28 patients (37%), diagnosis was based on pulmonary function tests, CT scans of the chest, or a combination of both. On multivariate analysis, the factors that were associated with an increased risk for BO included the following: peripheral blood-derived stem cell, a busulfan-based conditioning regimen, interval from diagnosis to transplant ≥ 14 months, female donor to male recipient sex match, prior interstitial pneumonitis, and an episode of moderate-to-severe acute graft-vs-host disease (GVHD).

Conclusion: In addition to corroborating previously reported risk factors, such as acute GVHD and a busulfan-based conditioning regimen, we found that peripheral blood stem-cell transplantation, long duration to transplant, female donor to male recipient, and a prior episode of interstitial pneumonitis are associated with an increased risk for BO.

Key Words: bone marrow transplantation • chronic airflow obstruction • obstructive lung disease • peripheral blood stem cell transplantation






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