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Methotrexate + cytarabine is a combination of two chemotherapy agents commonly used in the treatment of various hematological malignancies, including acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma, and primary central nervous system lymphoma (PCNSL)[2][5][6]. Methotrexate is an antimetabolite that inhibits enzymes involved in nucleotide synthesis—primarily dihydrofolate reductase—thereby preventing DNA synthesis and cell division[8]. Cytarabine is a nucleoside analog that interferes with DNA synthesis by inhibiting DNA polymerase. The combination exploits their complementary mechanisms to target rapidly dividing cancer cells. Sequential administration (methotrexate followed by cytarabine) has been shown to be synergistic in preclinical studies[6]. Both drugs are widely used as part of multi-agent regimens for hematologic cancers.
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