Autologous bone-marrow transplantation: host effects of high-dose BCNU

Thirty-five patients with solid tumors received 44 courses of bis-chlorethylnitrosourea (BCNU) at doses ranging between 600 and 1,400 mg/m2 with cryopreserved or fresh autologous bone-marrow support. Eight patients treated at 600 mg/m2 received no bone-marrow support for their first course of BCNU. Maximum follow-up was 25 months (median, four months). Myelosuppression was severe and dose related but was less prolonged in the marrow-supported groups (p = 0.01) and was not dose limiting. Myelosuppression-related toxicity of infection and hemorrhage occurred in 21 (47%) of 44 courses of treatment. Pulmonary toxicity occurred in seven of 35 patients; abnormal liver function occurred in 18 of 30 patients greater than one month from treatment; and central nervous system symptoms that may have been drug related occurred in six of 35 patients. There was no renal or cardiac toxicity. Except for myelosuppression, toxicity was not dose related. Treatment-related deaths included four with pulmonary toxicity, two with liver toxicity, sepsis in four, and gastrointestinal tract toxicity in one patient. We conclude that the limiting side effect of high-dose BCNU (greater than or equal to 600 mg/m2) is visceral toxicity; the extent of myelosuppression is shortened by the infusion of bone marrow, whether cryopreserved or fresh; and marked tumor regression can be achieved with high-dose BCNU.