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Methotrexate + 6-mercaptopurine is a combination of two antimetabolite chemotherapeutic agents commonly used in the maintenance therapy of acute lymphoblastic leukemia (ALL), particularly in pediatric patients. Methotrexate inhibits dihydrofolate reductase, leading to impaired DNA synthesis and cell replication. 6-Mercaptopurine is a purine analog that interferes with nucleotide synthesis and metabolism, further inhibiting DNA and RNA production. The combination acts synergistically by targeting different steps in the purine biosynthesis pathway, resulting in enhanced cytotoxicity against malignant lymphoblasts[1][2][4]. This regimen has been shown to improve remission rates compared to monotherapy but may increase the risk of certain toxicities or secondary malignancies depending on dose intensity and patient-specific factors such as thiopurine methyltransferase activity[2]. The drugs are typically administered orally during maintenance phases following induction chemotherapy for ALL.
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