title: Cytostatic conditioning in experimental allogeneic bone marrow transplantation: Busulfan causes less early gastrointestinal toxicity but Treosulfan results in improved immune reconstitution.
abstract: BACKGROUND
  Acute graft versus host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT) is associated with significant morbidity and mortality. We evaluated the impact of the conditioning regimen on aGVHD comparing Treosulfan (Treo) and Busulfan (Bu) with total body irradiation (TBI).
  
  
  METHODS
  Using a haploidentical murine model, B6D2F1 mice conditioned with Bu (100 mg/kg)/Fludarabine (Flu, 500 mg/kg) or Treo (6000 mg/kg)/Flu (500 mg/kg) or TBI with 14 Gy received bone marrow cells and splenocytes (20 × 10(6)) from either syngeneic (B6D2F1) or allogeneic (C57BL/6N) donors in order to analyze aGVHD outcome.
  
  
  RESULTS
  Conditioning with Bu/Flu or Treo/Flu resulted in significantly reduced aGVHD severity and improved survival (p < 0.05) after allo-BMT compared to TBI. On day 5 after allo-BMT, the organ damages of Bu/Flu conditioned animals were significantly reduced in association with diminished expression of tumor necrosis factor in serum compared to Treo/Flu. Interestingly, the early toxicity of Treo/Flu did not result in significantly higher aGVHD severity; furthermore, a significantly improved immune reconstitution of B220-positive B cells was observed at day 42 after Treo/Flu conditioning compared to Bu/Flu.
  
  
  CONCLUSIONS
  Conditioning with Treo/Flu or Bu/Flu results in decreased aGVHD severity compared to TBI. Moreover, Treo/Flu was associated with improved immune reconstitution despite the early toxicity.
authors.affiliation: Department of Hematology and Oncology, University of Regensburg Medical School , Regensburg , Germany and.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Bouazzaoui
authors.forename: Sabine
authors.initials: S
authors.lastname: Dickhöfer
authors.forename: Marina
authors.initials: M
authors.lastname: Kreuz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Huber
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000379:methods; D002066:Busulfan / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology*; D054697:Cytostatic Agents / Q000276:immunology* / Q000494:pharmacology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006086:Graft vs Host Disease / Q000139:chemically induced* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019172:Transplantation Conditioning / Q000379:methods; D014916:Whole-Body Irradiation / Q000379:methods
chemical_list: D054697:Cytostatic Agents; D007166:Immunosuppressive Agents; C018404:treosulfan; D002066:Busulfan