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This combination chemotherapy regimen, evaluated by the University of Rochester, integrates the CLAG protocol (cladribine, cytarabine, and filgrastim) with the tyrosine kinase inhibitor imatinib mesylate (Gleevec). It is designed for patients with relapsed or refractory acute myeloid leukemia (AML) or chronic myeloid leukemia in blastic phase (CML-BP). The regimen utilizes cladribine and cytarabine to inhibit DNA synthesis, while filgrastim (G-CSF) is used to prime leukemic blasts, potentially increasing their sensitivity to the cytotoxic agents. Imatinib mesylate is added to target specific receptors expressed on AML blasts, including c-kit, c-fms, and PDGFR, as well as the BCR-ABL fusion protein in CML cases. Preclinical data suggested synergy between cytarabine and imatinib, leading to the clinical investigation of this multi-agent approach which demonstrated acceptable toxicity and an overall response rate of 43.8% in early trials.
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