Transforming Growth Factor β as a Predictor of Liver and Lung Fibrosis after Autologous Bone Marrow Transplantation for Advanced Breast Cancer

Abstract

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 β (TGFβ) has been implicated in the pathogenesis of fibrosis. Methods: Using acid-ethanol extraction to remove TGFβ from human plasma and a mink-lung epithelial-cell growth-inhibition assay to measure TGFβ activity, we quantified plasma TGFβ 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 TGFβ levels between the controls and the patients who did not have hepatic veno-occlusive disease or idiopathic interstitial pneumonitis after transplantation. In contrast, pretransplantation TGFβ 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 TGFβ levels were more than 2 SD above the mean established in the controls. Conclusions: The plasma TGFβ 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., Hepatic veno-occlusive disease is a serious consequence of high-dose chemotherapy or radiotherapy combined with bone marrow transplantation for neoplasia; it occurs in 15 to 50 percent of patients, with a mortality rate of up to 50 percent1–7. The syndrome typically develops one to three weeks after transplantation and is characterized by sudden weight gain, hepatomegaly, ascites, and hyperbilirubinemia7; hepatic encephalopathy may also develop. Similarly, pulmonary complications of bone marrow-transplantation are a major source of morbidity, occurring in 40 to 60 percent of patients8. Noninfectious pulmonary complications (idiopathic interstitial pneumonitis) occur in 10 to 25 percent of… © 1993, Massachusetts Medical Society. All rights reserved.