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This combination immunochemotherapy regimen was developed by the National Cancer Institute (NCI) specifically for the treatment of AIDS-related primary central nervous system lymphoma (PCNSL). The protocol integrates high-dose methotrexate (HD-MTX), an antifolate small molecule that inhibits dihydrofolate reductase to arrest DNA synthesis, with rituximab, a monoclonal antibody targeting CD20-positive B-cells. Leucovorin is administered as a rescue agent to mitigate systemic toxicity from high-dose methotrexate. Crucially, the regimen is combined with Highly Active Antiretroviral Therapy (HAART) to manage the underlying HIV infection and promote immune reconstitution. This approach was designed to provide effective lymphoma control while minimizing T-cell toxicity in immunocompromised patients with severe CD4+ T-cell lymphopenia.
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