Pharmacodynamic Monitoring of Cancer Chemotherapy: Childhood Acute Lymphoblastic Leukemia as a Model

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Childhood acute lymphoblastic leukemia (ALL) has long served as a model of disseminated cancer that can be cured with chemotherapy. Although pharmacokinetic variability has been shown to influence the efficacy of ALL chemotherapy, the usefulness of conventional pharmacokinetic measures to predict responses to individual chemotherapeutic agents can be confounded in the context of multiagent chemotherapy. This has led to the concomitant use of pharmacodynamic endpoints to identify patients who exhibit a poor initial response to therapy or whose residual disease has a persistence that predicts a poor prognosis unless therapy is changed. To this end, the initial reduction of leukemia cells in peripheral blood or in bone marrow and the detection of minimal residual disease by immunologic or polymerase chain reaction-based methods have shown promise as pharmacodynamic endpoints to identify patients who are at high risk for relapse if therapy remains unchanged. Prospective clinical trials are needed to determine the clinical usefulness of pharmacodynamic monitoring and to define more precisely the integration of pharmacokinetic and pharmacodynamic monitoring and to optimize the treatment of childhood ALL.

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