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Gemcitabine + busulfan + thiotepa is a **high-dose chemotherapy regimen** combining three active agents: gemcitabine (a nucleoside analog antimetabolite), busulfan (an alkylating agent), and thiotepa (an alkylating agent). This regimen is primarily utilized as a conditioning treatment prior to **hematopoietic stem cell transplantation** or as salvage therapy for **hematologic malignancies** and some solid tumors. - **Gemcitabine** acts by inhibiting DNA synthesis, leading to cell death in rapidly dividing malignant cells. - **Busulfan** and **thiotepa** both induce DNA crosslinking and strand breakage, resulting in cell cycle arrest and apoptosis. The combination leverages different mechanisms of DNA damage and cell kill, providing synergistic cytotoxicity, especially in refractory or relapsed lymphoma and other aggressive cancers. This regimen is investigational and has been studied in phase 1 and 2 trials for use in **lymphoid tumors**, **neuroblastoma**, and primary or refractory central nervous system lymphoma, often with the goal of improving response rates prior to stem cell rescue[1][2][3][4].
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