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


METHODS
Using acid-ethanol extraction to remove TGF beta from human plasma and a mink-lung epithelial-cell growth-inhibition assay to measure TGF beta activity, we quantified plasma TGF beta 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 beta 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 beta 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 beta levels were more than 2 SD above the mean established in the controls.


CONCLUSIONS
The plasma TGF beta 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.
Anscher
M S
MS
Department of Radiation Oncology, Duke University Medical School, Durham, N.C. 27710.
Peters
W P
WP
Reisenbichler
H
H
Petros
W P
WP
Jirtle
R L
RL
D000230:Adenocarcinoma / Q000601:surgery* / Q000628:therapy; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000601:surgery* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000175:diagnosis / Q000209:etiology / Q000276:immunology; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood*
D016212:Transforming Growth Factor beta