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 ma rrow 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 t o remove TGFbeta from human plasma and a mink-lung epithelial-cell gro wth-inhibition assay to measure TGFbeta activity, we quantified plasma TGFbeta in 10 normal subjects and 41 patients before and after they u nderwent high-dose chemotherapy and autologous bone marrow transplanta tion for advanced breast cancer. Results. There was no difference in p retransplantation TGFbeta levels between the controls and the patients who did not have hepatic veno-occlusive disease or idiopathic interst itial pneumonitis after transplantation. In contrast, pretransplantati on TGFbeta levels were significantly higher in patients in whom hepati c veno-occlusive disease or idiopathic interstitial pneumonitis develo ped than in the controls or the patients without these conditions. The predictive value for the development of either condition was 90 perce nt or more when pretransplantation plasma TGFbeta levels were more tha n 2 SD above the mean established in the controls. Conclusions. The pl asma TGFbeta concentration measured after induction chemotherapy but b efore high-dose chemotherapy and autologous bone marrow transplantatio n strongly correlates with the risk of hepatic veno-occlusive disease and idiopathic interstitial pneumonitis after these treatments.