Evaluation of Temozolomide in a SCID Mouse Model of Human B-Cell Precursor Leukemia

Abstract

We used a SCID mouse model of human B-lineage acute lymphoblastic leukemia to examine the antileukemic activity of temozolomide in comparison to as well as in combination with B43-PAP anti-CD 19 immunotoxin. One hundred percent of the 20 PBS-treated control mice died of disseminated human B-lineage ALL at 32 to 64 days after the inoculation of 1×106 NALM-6 cells, with a median event free survival time of 43 ± 1 days. Temozolomide, when administered i.p. for 5 consecutive days at a dose level of 411 mg/m2 or as a single 750 mg/m2 bolus dose, elicited significant antileukemic activity and improved survival in this SCID mouse model of human B-lineage ALL. The median survival times were 43 ± 1 days for PBS-treated mice, 56 ± 16 days for mice injected with the 5-day temozolomide program, and 64 ± 15 days for mice treated with a single bolus dose of temozolomide. However, temozolomide was not as effective as B43-PAP. Whereas only 40 ± 21% of mice treated with temozolomide survived beyond 120 days, B43-PAP treatment resulted in 74 ± 7% survival in the same model system. The combination of temozolomide with B43-PAP was well tolerated by mice but it was not significantly more effective than B43-PAP alone. Temozolomide may have very limited potential as an antileukemic agent for treatment of B-lineage ALL