Background Hepatic veno-occlusive disease and idiopathic interstitialpneumonitis are major causes of morbidity and mortality afterbone marrow transplantation. Fibrosis is a characteristic ofboth conditions, and transforming growth factor (TGF) has beenimplicated in the pathogenesis of fibrosis.
Methods Using acid-ethanol extraction to remove TGF from humanplasma and a mink-lung epithelial-cell growth-inhibition assayto measure TGF activity, we quantified plasma TGF in 10 normalsubjects and 41 patients before and after they underwent high-dosechemotherapy and autologous bone marrow transplantation foradvanced breast cancer.
Results There was no difference in pretransplantation TGF levelsbetween the controls and the patients who did not have hepaticveno-occlusive disease or idiopathic interstitial pneumonitisafter transplantation. In contrast, pretransplantation TGF levelswere significantly higher in patients in whom hepatic veno-occlusivedisease or idiopathic interstitial pneumonitis developed thanin the controls or the patients without these conditions. Thepredictive value for the development of either condition was90 percent or more when pretransplantation plasma TGF levelswere more than 2 SD above the mean established in the controls.
Conclusions The plasma TGF concentration measured after inductionchemotherapy but before high-dose chemotherapy and autologousbone marrow transplantation strongly correlates with the riskof hepatic veno-occlusive disease and idiopathic interstitialpneumonitis 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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