title: Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage.
abstract: 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 × 107bone marrow cells and 2 × 107splenocytes 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-γexpression 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.
authors.affiliation: Department of Hematology, Zhongshan Hospital of Sun Yat-Sen University and Zhongshan City People's Hospital, Zhongshan 528403, China.
authors.forename: Xin
authors.identifier: 0000-0003-4328-2805
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Hematology, Zhongshan Hospital of Sun Yat-Sen University and Zhongshan City People's Hospital, Zhongshan 528403, China.
authors.forename: YongBin
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Hematology, Zhongshan Hospital of Sun Yat-Sen University and Zhongshan City People's Hospital, Zhongshan 528403, China.
authors.forename: XiaoJun
authors.identifier: 0000-0001-5030-7201
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: YuXian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: GuangYang
authors.initials: G
authors.lastname: Weng
authors.affiliation: Department of Hematology, Zhongshan Hospital of Sun Yat-Sen University and Zhongshan City People's Hospital, Zhongshan 528403, China.
authors.forename: MingWan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: KunYuan
authors.identifier: 0000-0003-1943-3132
authors.initials: K
authors.lastname: Guo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005786:Gene Expression Regulation / Q000187:drug effects; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000097:blood; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects; D014184:Transplantation, Homologous / Q000009:adverse effects; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D004338:Drug Combinations; D015847:Interleukin-4; D007371:Interferon-gamma; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine