TRANSFORMING GROWTH-FACTOR-BETA AS A PREDICTOR OF LIVER AND LUNG FIBROSIS AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR ADVANCED BREAST-CANCER

Background. Hepatic veno-occlusive disease and idiopathic interstitial pneumonitis are major causes of morbidity and mortality after bone marrow transplantation. Fibrosis is a characteristic of both conditions, and transforming growth factor beta (TGFbeta) has been implicated in the pathogenesis of fibrosis. Methods. Using acid-ethanol extraction to remove TGFbeta from human plasma and a mink-lung epithelial-cell growth-inhibition assay to measure TGFbeta activity, we quantified plasma TGFbeta in 10 normal subjects and 41 patients before and after they underwent high-dose chemotherapy and autologous bone marrow transplantation for advanced breast cancer. Results. There was no difference in pretransplantation TGFbeta levels between the controls and the patients who did not have hepatic veno-occlusive disease or idiopathic interstitial pneumonitis after transplantation. In contrast, pretransplantation TGFbeta levels were significantly higher in patients in whom hepatic veno-occlusive disease or idiopathic interstitial pneumonitis developed than in the controls or the patients without these conditions. The predictive value for the development of either condition was 90 percent or more when pretransplantation plasma TGFbeta levels were more than 2 SD above the mean established in the controls. Conclusions. The plasma TGFbeta concentration measured after induction chemotherapy but before high-dose chemotherapy and autologous bone marrow transplantation strongly correlates with the risk of hepatic veno-occlusive disease and idiopathic interstitial pneumonitis after these treatments.