title: Preclinical analysis of treosulfan in combination with total body irradiation as conditioning regimen prior to bone marrow transplantation in rats.
abstract: Treosulfan (Treo) and total body irradiation (TBI) demonstrate a high therapeutic activity in treatment of acute leukemia and lymphoma. We investigated the combination of Treo and TBI prior to bone marrow transplantation (BMT) in rats. Female Lewis rats were treated with Treo on 3 consecutive days followed by TBI with either 5 Gy (n = 28) or 7.5 Gy (n = 48). After conditioning animals received 4 x 10E7 bone marrow cells (BC) from female Lewis rats. Additional 16 rats were transplanted with 4 x 10E7 BC and 1.5 x 10E7 spleen T-cells from female Brown-Norway (BN) rats. Animals were examined daily for clinical signs and toxicity was investigated by necropsy and histology in all animals. Gastrointestinal toxicity was the dose-limiting factor of Treo in combination with TBI. The highest tolerable dose of Treo in combination with 7.5 Gy TBI was 3 x 0.5 g/kg and the highest tolerable dose of Treo in combination with 5 Gy TBI was 3 x 0.6 g/kg. Allogeneic BMT from BN donors resulted in engraftment and survival of 12 out of 16 animals. Gastrointestinal toxicity is the dose-limiting factor in the treatment with Treo and TBI. Furthermore, Treo possesses certain characteristics of a radiosensitizer.
authors.affiliation: Department of Hematology and Oncology, Department of Medicine, University of Rostock, Rostock, Germany.
authors.forename: Vicky
authors.initials: V
authors.lastname: Sender
authors.forename: Nicole
authors.initials: N
authors.lastname: Hofmeister-Mielke
authors.forename: Kathrin
authors.initials: K
authors.lastname: Sievert
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Teifke
authors.forename: Heike
authors.initials: H
authors.lastname: Vogel
authors.forename: Joachim
authors.initials: J
authors.lastname: Baumgart
authors.forename: Uwe
authors.initials: U
authors.lastname: Pichlmeier
authors.forename: Mathias
authors.initials: M
authors.lastname: Freund
authors.forename: Jochen
authors.initials: J
authors.lastname: Casper
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods; D002066:Busulfan / Q000031:analogs & derivatives* / Q000494:pharmacology; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D019172:Transplantation Conditioning / Q000379:methods; D014916:Whole-Body Irradiation / Q000379:methods
chemical_list: C018404:treosulfan; D002066:Busulfan