Asparaginase-associated myelosuppression and effects on dosing of other chemotherapeutic agents in childhood acute lymphoblastic leukemia

Abstract

Although L-asparaginase (ASP) is associated with several toxicities, its myelosuppressive effect has not been well characterized. On DFCI ALL Consortium Protocol 05-01 for children with newly diagnosed acute lymphoblastic leukemia, the Consolidation phase and the initial portion of the Continuation phase were identical for standard risk patients, except ASP was given only during Consolidation. Comparing the two treatment phases revealed that low blood counts during Consolidation with ASP resulted in more dosage reductions of 6-mercaptopurine and methotrexate. The myelosuppressive effect of ASP should be considered when designing treatment regimens to avoid excessive toxicity and dose reductions of other critical chemotherapy agents.

A: Dosing of methotrexate during post-induction chemotherapy cycles. Starting dose of methotrexate for all patients was 30 mg/m2/week (100% dose). Methotrexate doses were subsequently kept the same, reduced (40–90% of starting dose), or escalated (110–150% of starting dose) depending on blood counts during the previous 21-day chemotherapy cycle. B: Dosing of 6-mercaptopurine during post-induction chemotherapy cycles. Starting dose of 6-mercaptopurine for all patients was 50 mg/m2/day (100% dose) for days 1–14 days of every 3-week cycle. 6-MP doses were subsequently kept the same, reduced (40–90% of starting dose), or escalated (110–150% of starting dose) depending on blood counts during the previous 21-day chemotherapy cycle.