Efficacy and Toxicity of Asparaginases During Prospective Drug Monitoring in Patients With Childhood Acute Lymphoblastic Leukemia

Abstract

Intensified and effective asparaginase therapy is very important in modern treatment of childhood acute lymphoblastic leukemia. The use of native E.coli asparaginase in induction leads to a high rate of hypersensitivity reactions to PEGasparaginase in the intensification phase of the Dutch Childhood Oncology Group ALL-10 medium risk protocol. Based on this research, the starting PEGasparaginase dose in the ongoing ALL-11 protocol has been lowered to 1,500 IU/m2 because of the high asparaginase trough levels which were found in the ALL-10 protocol. This dose reduction of PEGasparaginase should be guided by careful monitoring of asparaginase activity levels. Currently, a nation-wide therapeutic drug monitoring (TDM) program is used to individualize the PEGasparaginase dose and to detect silent inactivation. In case of an allergy to or silent inactivation of PEGasparaginase, patients are switched to Erwinia asparaginase with TDM to allow individualized dosing of Erwinia asparaginase.