Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage
| Autor: | Yongbin Ye, Yuxian Huang, Jing Wang, Kun-Yuan Guo, Mingwan Zhang, Xin He, Guangyang Weng, Xiaojun Xu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Article Subject T-Lymphocytes medicine.medical_treatment lcsh:Medicine Graft vs Host Disease Bone Marrow Cells Hematopoietic stem cell transplantation General Biochemistry Genetics and Molecular Biology Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Splenocyte Animals Humans Transplantation Homologous Busulfan Cyclophosphamide Bone Marrow Transplantation General Immunology and Microbiology business.industry lcsh:R Hematopoietic Stem Cell Transplantation General Medicine Fludarabine Transplantation Disease Models Animal Drug Combinations Regimen surgical procedures operative 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Immunology Conditioning Interleukin-4 Bone marrow business Vidarabine Research Article 030215 immunology medicine.drug |
| Zdroj: | BioMed Research International BioMed Research International, Vol 2016 (2016) |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2016/3071214 |
| Popis: | Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a major cause of nonrelapse mortality after allo-HSCT. A conditioning regimen plays a pivotal role in the development of aGVHD. To provide a platform for studying aGVHD and evaluating the impact of different conditioning regimens, we established a murine aGVHD model that simulates the clinical situation and can be conditioned with Busulfan-Cyclophosphamide (Bu-Cy) and Fludarabine-Busulfan (Flu-Bu). In our study, BALB/c mice were conditioned with Bu-Cy or Flu-Bu and transplanted with 2×107 bone marrow cells and 2×107 splenocytes from either allogeneic (C57BL/6) or syngeneic (BALB/c) donors. The allogeneic recipients conditioned with Bu-Cy had shorter survivals (P<0.05), more severe clinical manifestations, and higher hepatic and intestinal pathology scores, associated with increased INF-γ expression and diminished IL-4 expression in serum, compared to allogeneic recipients conditioned with Flu-Bu. Moreover, higher donor-derived T-cell infiltration and severely impaired B-cell development were seen in the bone marrow of mice, exhibiting aGVHD and conditioned with Flu-Bu. Our study showed that the conditioning regimen with Bu-Cy resulted in more severe aGVHD while the Flu-Bu regimen was associated with more extensive and long standing bone marrow damage. |
| Databáze: | OpenAIRE |
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