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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.

Abstract
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.
AuthorsA Abdul-Hai, L Weiss, D Ergas, I B Resnick, S Slavin, M Y Shapira
JournalBone marrow transplantation (Bone Marrow Transplant) Vol. 40 Issue 9 Pg. 891-6 (Nov 2007) ISSN: 0268-3369 [Print] England
PMID17768389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cyclophosphamide
  • Thiotepa
  • Busulfan
Topics
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Busulfan (therapeutic use)
  • Cyclophosphamide (therapeutic use)
  • Disease Models, Animal
  • Drug Synergism
  • Hematopoietic Stem Cell Transplantation (methods)
  • Leukemia, B-Cell (drug therapy)
  • Mice
  • Mice, Inbred BALB C
  • Thiotepa (therapeutic use)
  • Transplantation, Autologous
  • Treatment Outcome

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