UNDETECTED VIRAL-INFECTION IN DIFFUSE ALVEOLAR DAMAGE ASSOCIATED WITHBONE-MARROW TRANSPLANTATION

To investigate the presence of nondiagnosed viral lung infections in p atients who developed acute respiratory failure and diffuse pulmonary infiltrates after bone marrow transplantation (BMT), we studied necrop sy-obtained lung specimens with features of diffuse alveolar damage (D AD) where no other specific histological diagnosis could be establishe d, by using in situ hybridization and immunohistochemistry. Lung tissu e samples obtained at necropsy from 19 patients (12 males and 7 female s; 31+/-11 yrs mean+/-SD age) who died 56+/-36 days after BMT (12 allo geneic and 7 autologous), were studied retrospectively using specific deoxyribonucleic acid (DNA) probes to detect cytomegalovirus (CMV), he rpes simplex virus (HSV), Epstein-Barr virus (EBV), and adenovirus gen omes, Tissue samples were additionally processed with antibodies to CM V and HSV antigens. Cells infected by CMV were detected by in situ hyb ridization in five cases, and by immunohistochemistry in four cases, C ombining the results of both procedures, a previously undiagnosed CMV infection was found in six patients, All of them had received an allog eneic BMT and had developed graft-versus-host disease (GVHD), No evide nce of cells infected by HSV, EBV, or adenovirus was found in any case , No viral infection was detected either in recipients of autologous m arrow or in recipients of allogeneic BMT without GVHD. These results i ndicate that pulmonary cytomegalovirus infection not detected by conve ntional histological examination may be present in patients with diffu se alveolar damage associated with bone marrow transplantation, especi ally in recipients of allogeneic marrow who develop graft-versus-host disease, Furthermore, the use of in situ hybridization and/or immunohi stochemistry on pulmonary histology might improve the diagnosis of vir al lung infections in patients receiving bone marrow transplantation.