Long-term follow-up of myeloablative allogeneic stem cell transplantation using Campath 'in the bag' as T-cell depletion: the Leiden experience

Long-term follow-up of myeloablative allogeneic stem cell transplantation using Campath 'in the bag' as T-cell depletion: the Leiden experience
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DOI:
10.1038/sj.bmt.1705385
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发表时间:
2006-06-01
影响因子:
4.8
通讯作者:
Willemze, R
Willemze, R
中科院分区:
医学3区
文献类型:
--
作者:
Barge, RMY;Starrenburg, CWJ;Willemze, R

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移植物抗宿主病(GVHD)是异体干细胞移植(allogenic stem cell transplantation, alloSCT)后死亡和发病的主要原因,但可以通过移除移植物中的t淋巴细胞来预防。Campath(抗cd52)抗体已在体内广泛用于常规和低强度调理方案后的t细胞耗竭。Campath在体内的使用与GVHD的显著降低相关,但代价是免疫重建受损。我们使用Campath“in the bag”作为体外t细胞清除方法,评估了73例hla相同的兄弟姐妹供体的骨髓同种异体干细胞移植的长期结果。所有患者移植后,造血功能恢复顺利,在同种异体干细胞移植后3个月,供体嵌合率中位数为99%。巨细胞病毒(CMV)再激活发生在53%的患者中。未观察到巨细胞病毒疾病,可能是先发制人(val)更昔洛韦治疗的结果。aGVHD的发生率较低(22%为II级)。未观察到III-IV级aGVHD, 19%的患者发生广泛的慢性GVHD (cGVHD)。GVHD的低发病率和成功的预防性抗病毒治疗导致TRM低至8%。16例患者因同种异体移植后疾病复发而死亡,导致同种异体移植后5年的总生存率为48%。
Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic stem cell transplantation (alloSCT) but can be prevented by removing T-lymphocytes from the graft. Campath (anti-CD52) antibodies have been widely used in vivo for T-cell depletion following conventional and reduced intensity conditioning regimens. The use of Campath in vivo was associated with a significant reduction in GVHD but at the cost of impaired immune reconstitution. We evaluated the long-term outcome of 73 myeloablative allogeneic stem cell transplants with HLA-identical sibling donors using Campath 'in the bag' as method of in vitro T-cell depletion. All patients engrafted and hematopoietic recovery was uneventful, resulting in a median of 99% donor chimerism at 3 months after alloSCT. Cytomegalovirus ( CMV) reactivation occurred in 53% of the patients. No CMV disease was observed probably as a result of pre-emptive (val) ganciclovir treatment. The incidence of aGVHD was low (22% grade II). No grades III-IV aGVHD was observed and extensive chronic GVHD (cGVHD) occurred in 19% of the patients. The low incidence of GVHD and successful pre-emptive antiviral therapy resulted in low TRM of 8%. Sixteen patients died due to disease relapse after alloSCT, resulting in an overall survival of 48% at 5-years after alloSCT.