CHANGES IN PLASMA TRANSFORMING GROWTH-FACTOR-BETA IN RESPONSE TO HIGH-DOSE CHEMOTHERAPY FOR STAGE-II BREAST-CANCER - POSSIBLE IMPLICATIONS FOR THE PREVENTION OF HEPATIC VENOOCCLUSIVE DISEASE AND PULMONARY DRUGTOXICITY

Veno-occlusive disease (VOD) of the liver and pulmonary drug toxicity (PDT) are two major complications of high-dose chemotherapy and autolo gous bone marrow transplantation (BMT) for solid tumors, We have previ ously demonstrated that an elevated plasma TGF-beta concentration befo re transplant predicts the later occurrence of these complications. In the present study, we used a simplified enzyme-linked immunosorbant a ssay (ELISA) to prospectively evaluate the kinetics of plasma TGF-beta concentrations of 45 patients with stage II breast cancer who underwe nt high-dose chemotherapy and autologous BMT. We demonstrated that, of the three TGF-beta isoforms, only TGF-beta 1 was present in the plasm a. Pre-transplant plasma TGF-beta 1 was significantly higher in patien ts with VOD and PDT compared with that in patients without these compl ications, The plasma TGF-beta 1 level in patients who later developed VOD or PDT decreased to that of controls within 2 days of initiating h igh-dose chemotherapy; this decrease was not correlated with platelet concentration changes. These results suggest that interventions aimed at preventing the development at VOD or PDT must be given early in the course of high-dose chemotherapy.