The effect of high-dose thiotepa, alone or in combination with other chemotherapeutic agents, on a murine B-cell leukemia model simulating autologous stem cell transplantation: Pre-Clinical Studies

The use of thiotepa (TH) is increasing, especially in stem cell transplantation, mainly due to its safety and blood–brain barrier penetration. We evaluated the use of TH in a murine model simulating autologous stem cell transplantation, with or without additional agents. Between 1 and 11 days follow...

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Veröffentlicht in:Bone marrow transplantation (Basingstoke) 2007, Vol.40 (9), p.891-896
Hauptverfasser: Abdul-Hai, A, Weiss, L, Ergas, D, Resnick, I B, Slavin, S, Shapira, M Y
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Sprache:eng
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Zusammenfassung:The use of thiotepa (TH) is increasing, especially in stem cell transplantation, mainly due to its safety and blood–brain barrier penetration. We evaluated the use of TH in a murine model simulating autologous stem cell transplantation, with or without additional agents. Between 1 and 11 days following inoculation of BALB/c mice with 10 5 –10 8 B-cell leukemia (BCL1) cells (simulating pre-transplant leukemia loads), each group received an ‘induction-like’ irradiation and/or cytotoxic regimen. Animals were either followed without treatment, or an adoptive transfer (AT) was performed to untreated BALB/c mice. Administered alone without AT, high-dose TH did not change the time to appearance of leukemia. Nevertheless, in the AT experiments, TH as a single agent showed better antileukemic activity than busulfan (BU). Cyclophosphamide (CY)-containing regimens were the most effective, and the TH–CY combination was as effective as the commonly used BU–CY combination, and more effective than the BU–TH combination. Moreover, a synergistic effect was seen in the TH–CY combination (none of the animals developed leukemia, whereas 4/10 animals in the CY–TBI group developed leukemia ( P =0.029)). In conclusion, although TH produced only a moderate effect against BCL1 leukemia when used alone, its combination with CY is promising and should be tested further in allogeneic murine models and clinical studies.
ISSN:0268-3369
1476-5365
DOI:10.1038/sj.bmt.1705838