Late CD8+ Lymphocytic Alveolitis After Allogeneic Bone Marrow Transplantation and Chronic Graft-Versus-Host Disease

Abstract

Late-onset interstitial pneumonitis following allogeneic bone marrow transplantation (BMT) is a rare condition usually caused by a variety of infective agents, although in some cases these are idiopathic. We investigated noninfectious late interstitial pneumonitis with lymphocytic alveolitis in seven allogeneic BMT recipients using bronchoalveolar lavage (BAL), lymphocyte phenotyping analysis, CT lung scans, and pulmonary function tests. The results were compared with those of a control group composed of similar patients with no pulmonary symptoms. Of 65 long-term survivors, seven were included in the study. All had chronic graft-versus-host disease (GVHD) and developed interstitial pneumonitis a median of 210 d (range 120 to 445 d) after BMT. BAL revealed lymphocytosis, with an overall expansion of CD8+ subsets (38 to 90%). Lymphocytic alveolitis was not observed in the control group. Pulmonary function tests revealed a restrictive syndrome, and biopsy samples obtained from 2 patients showed interstitial lymphoid infiltration with fibrosis of the alveolar walls. Of the 7 patients, six were cured by starting immunosuppressive drugs or increasing the dosage with a drastic improvement in respiratory symptoms within 1 mo. These findings suggest that CD8+ alveolitis may be observed in late interstitial pneumonitis in allogeneic BMT recipients and may be a pulmonary manifestation of chronic GVHD.