Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage
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 aGV...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2016-01-01
|
Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2016/3071214 |
id |
doaj-7743ea58d9f14d9f91d98bbd7068e6c5 |
---|---|
record_format |
Article |
spelling |
doaj-7743ea58d9f14d9f91d98bbd7068e6c52020-11-24T23:59:46ZengHindawi LimitedBioMed Research International2314-61332314-61412016-01-01201610.1155/2016/30712143071214Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow DamageXin He0YongBin Ye1XiaoJun Xu2Jing Wang3YuXian Huang4GuangYang Weng5MingWan Zhang6KunYuan Guo7Department of Hematology, Zhongshan Hospital of Sun Yat-Sen University and Zhongshan City People’s Hospital, Zhongshan 528403, ChinaDepartment of Hematology, Zhongshan Hospital of Sun Yat-Sen University and Zhongshan City People’s Hospital, Zhongshan 528403, ChinaDepartment of Hematology, Zhongshan Hospital of Sun Yat-Sen University and Zhongshan City People’s Hospital, Zhongshan 528403, ChinaDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaDepartment of Hematology, Zhongshan Hospital of Sun Yat-Sen University and Zhongshan City People’s Hospital, Zhongshan 528403, ChinaDepartment of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, ChinaAcute 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.http://dx.doi.org/10.1155/2016/3071214 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xin He YongBin Ye XiaoJun Xu Jing Wang YuXian Huang GuangYang Weng MingWan Zhang KunYuan Guo |
spellingShingle |
Xin He YongBin Ye XiaoJun Xu Jing Wang YuXian Huang GuangYang Weng MingWan Zhang KunYuan Guo Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage BioMed Research International |
author_facet |
Xin He YongBin Ye XiaoJun Xu Jing Wang YuXian Huang GuangYang Weng MingWan Zhang KunYuan Guo |
author_sort |
Xin He |
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 |
title_short |
Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage |
title_full |
Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage |
title_fullStr |
Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage |
title_full_unstemmed |
Conditioning with Fludarabine-Busulfan versus Busulfan-Cyclophosphamide Is Associated with Lower aGVHD and Higher Survival but More Extensive and Long Standing Bone Marrow Damage |
title_sort |
conditioning with fludarabine-busulfan versus busulfan-cyclophosphamide is associated with lower agvhd and higher survival but more extensive and long standing bone marrow damage |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2016-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2016/3071214 |
work_keys_str_mv |
AT xinhe conditioningwithfludarabinebusulfanversusbusulfancyclophosphamideisassociatedwithloweragvhdandhighersurvivalbutmoreextensiveandlongstandingbonemarrowdamage AT yongbinye conditioningwithfludarabinebusulfanversusbusulfancyclophosphamideisassociatedwithloweragvhdandhighersurvivalbutmoreextensiveandlongstandingbonemarrowdamage AT xiaojunxu conditioningwithfludarabinebusulfanversusbusulfancyclophosphamideisassociatedwithloweragvhdandhighersurvivalbutmoreextensiveandlongstandingbonemarrowdamage AT jingwang conditioningwithfludarabinebusulfanversusbusulfancyclophosphamideisassociatedwithloweragvhdandhighersurvivalbutmoreextensiveandlongstandingbonemarrowdamage AT yuxianhuang conditioningwithfludarabinebusulfanversusbusulfancyclophosphamideisassociatedwithloweragvhdandhighersurvivalbutmoreextensiveandlongstandingbonemarrowdamage AT guangyangweng conditioningwithfludarabinebusulfanversusbusulfancyclophosphamideisassociatedwithloweragvhdandhighersurvivalbutmoreextensiveandlongstandingbonemarrowdamage AT mingwanzhang conditioningwithfludarabinebusulfanversusbusulfancyclophosphamideisassociatedwithloweragvhdandhighersurvivalbutmoreextensiveandlongstandingbonemarrowdamage AT kunyuanguo conditioningwithfludarabinebusulfanversusbusulfancyclophosphamideisassociatedwithloweragvhdandhighersurvivalbutmoreextensiveandlongstandingbonemarrowdamage |
_version_ |
1725446193118445568 |