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) and the value of adding etoposide to standard conditioning agents is being tested, The aim of the study was to assess the extramedullary toxicity which resulted from adding etoposide to busulphan 16 mg/kg and cyclophosphamide 120 mg/kg (BuCY2). Eighty four patients received etoposide 40 mg/kg in addition to BuCY2 as conditioning for autologous and allogeneic 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 six deaths (five alveolar hemorrhage and one pulmonary embolus). Five of seven of the patients with severe pulmonary toxicity had been given irradiation to the lung fields (P < 0.001), Thirty nine per cent of patients had veno-occlusive disease of the liver but the case fatality rate 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 toxicity, This regimen is associated with severe pulmonary toxicity in patients with a history of prior chest irradiation, A high incidence of skin toxicity was seen; a system for describing this toxicity is proposed.