Evaluation of temozolomide in a SCID mouse model of human B-cell precursorleukemia

We used a SCID mouse model of human B-lineage acute lymphoblastic leukemia to examine the antileukemic activity of temozolomide in comparison to as we ll as in combination with B43-PAP anti-CD19 immunotoxin. One hundred percen t of the 20 PBS-treated control mice died of disseminated human B-lineage A LL at 32 to 64 days after the inoculation of 1x10(6) NALM-6 cells, with a m edian event free survival time of 43 +/- 1 days. Temozolomide, when adminis tered i.p. for 5 consecutive days at a dose level of 411 mg/m(2) or as a si ngle 750 mg/m(2) bolus dose, elicited significant antileukemic activity and improved survival in this SCID mouse model of human B-lineage ALL. The med ian survival rimes were 43 +/- 1 days for PBS-treated mice, 56 +/- 16 days for mice injected with the 5-day temozolomide program, and 64 +/- 15 days f or mice treated with a single bolus dose of temozolomide. However, temozolo mide was not as effective as B43-PAP. Whereas only 40 +/- 21% of mice treat ed with temozolomide survived beyond 120 days, B43-PAP treatment resulted i n 74 +/- 7% survival in the same model system. The combination of temozolom ide with B43-PAP was well tolerated by mice but it was not significantly mo re effective than B43-PAP alone. Temozolomide may have very limited potenti al as an antileukemic agent for treatment of B-lineage ALL.