Effects of high-dose chemotherapy with syngeneic bone marrow transplantation in experimental brain tumor in rats.

Abstract

The clinical dose of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitro- sourea hydrochloride (ACNU) is limited by the bone marrow suppression it produces. The authors investigated whether bone marrow transplantation (BMT) associated with a high dose of ACNU could alleviate marrow toxicity and achieve greater antitumor effects in Fischer rats. High doses of ACNU (20, 25, and 30 mg/kg) were administered on day 1, followed by injection of syngeneic bone marrow cells on day 3. Patterns of leukocyte recovery were compared in BMT and non-BMT groups. There was a significant benefit in leukocyte recovery in the BMT groups. A 9L glioma that was sensitive to ACNU was transplanted into the brain tissue of rats. Seven days later, the animals were divided into three groups based on the dose of ACNU (2, 10, and 25 mg/kg). The median survival time increased with larger ACNU doses. This suggested that high-dose ACNU chemotherapy with BMT could achieve greater antitumor effects and less bone marrow suppression than high-dose ACNU alone.