Bouazzaoui, Abdellatif and Dickhoefer, Sabine and Kreuz, Marina and Huber, Elisabeth and Holler, Ernst and Wolff, Daniel (2014) Cytostatic conditioning in experimental allogeneic bone marrow transplantation: Busulfan causes less early gastrointestinal toxicity but Treosulfan results in improved immune reconstitution. IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY, 36 (2). pp. 158-164. ISSN 0892-3973, 1532-2513
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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 x 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. Conclusion: 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; TOTAL-BODY IRRADIATION; IDIOPATHIC-PNEUMONIA-SYNDROME; HEMATOLOGIC MALIGNANCIES; CHEMOKINE EXPRESSION; IFN-GAMMA; MICE; MACROPHAGES; CHIMERISM; Animal models; B cells; bone marrow transplantation; cytokines; experimental transplantation; T cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Nov 2019 13:58 |
| Last Modified: | 14 Nov 2019 13:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10339 |
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