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The combination of thiotepa, treosulfan, and fludarabine is a myeloablative conditioning regimen used prior to allogeneic hematopoietic stem cell transplantation (HSCT), particularly in pediatric and adult patients with hematological malignancies such as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia. This regimen leverages the synergistic effects of two alkylating agents—thiotepa and treosulfan—with the antimetabolite fludarabine to achieve profound immunosuppression and cytoreduction. Treosulfan and thiotepa act as DNA-alkylating agents causing cross-linking of DNA strands leading to cell death, while fludarabine inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase. The combination is associated with high rates of engraftment, low non-relapse mortality, effective disease control even in relapsed/refractory settings or second transplants after prior HSCT failure, and manageable toxicity profiles[1][2][6][8].
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