EXTRAMEDULLARY TOXICITY OF A CONDITIONING REGIMEN CONTAINING BUSULFAN, CYCLOPHOSPHAMIDE AND ETOPOSIDE IN 84 PATIENTS UNDERGOING AUTOLOGOUS AND ALLOGENEIC BONE-MARROW TRANSPLANTATION

Relapse is still a common problem after bone marrow transplant (BMT) a nd the value of adding etoposide to standard conditioning agents is be ing tested, The aim of the study was to assess the extramedullary toxi city which resulted from adding etoposide to busulphan 16 mg/kg and cy clophosphamide 120 mg/kg (BuCY2). Eighty four patients received etopos ide 40 mg/kg in addition to BuCY2 as conditioning for autologous and a llogeneic BMT for leukemia and lymphoma, The Bearman system of grading extramedullary toxicity was used along with a system of grading skin toxicity that we devised. There were seven acute toxic deaths (8%) and in total 15 patients experienced life-threatening or fatal toxicity, The major finding was a striking increase in pulmonary toxicity with s ix deaths (five alveolar hemorrhage and one pulmonary embolus). Five o f seven of the patients with severe pulmonary toxicity had been given irradiation to the lung fields (P < 0.001), Thirty nine per cent of pa tients had veno-occlusive disease of the liver but the case fatality r ate was low (1 of 33), Dermatologic toxicity was experienced by 82% of patients and was symptomatically troublesome but rapidly reversible, The addition of etoposide to BuCY2 increases non-hematological toxicit y, This regimen is associated with severe pulmonary toxicity in patien ts with a history of prior chest irradiation, A high incidence of skin toxicity was seen; a system for describing this toxicity is proposed.