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Previous Volume 328:1592-1598 June 3, 1993 Number 22 Next

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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 (TGF) has been implicated in the pathogenesis of fibrosis.

Methods Using acid-ethanol extraction to remove TGF from human plasma and a mink-lung epithelial-cell growth-inhibition assay to measure TGF activity, we quantified plasma TGF 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 TGF levels between the controls and the patients who did not have hepatic veno-occlusive disease or idiopathic interstitial pneumonitis after transplantation. In contrast, pretransplantation TGF 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 TGF levels were more than 2 SD above the mean established in the controls.

Conclusions The plasma TGF 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.

Source Information

From the Department of Radiation Oncology (M.S.A., H.R., R.L.J.) and the Department of Medicine, Division of Hematology-Oncology (W.P. Peters, W.P. Petros), Duke University Medical School, Durham, N.C.

Address reprint requests to Dr. Jirtle at Box 3433, Duke University Medical Center, Durham, NC 27710.

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