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使用Campath 1M进行体外T细胞清除,用于治疗重症联合免疫缺陷(SCID)的不匹配骨髓移植。

In vitro T cell depletion using Campath 1M for mismatched BMT for severe combined immunodeficiency (SCID).

作者信息

Dickinson A M, Reid M M, Abinun M, Peak J, Brigham K, Dunn J, Cant A J

机构信息

Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

出版信息

Bone Marrow Transplant. 1997 Feb;19(4):323-9. doi: 10.1038/sj.bmt.1700669.

DOI:10.1038/sj.bmt.1700669
PMID:9051241
Abstract

Bone marrow transplantation is the only curative treatment for children with severe combined immunodeficiency (SCID). In the absence of an HLA-identical sibling, haploidentical parental donor marrow can be used provided it is depleted of T cells to prevent otherwise inevitable GVHD. Campath 1M has been successfully used for this procedure in several centres. In our centre 17 SCID patients plus one with combined immunodeficiency (CID) were transplanted with Campath 1M T cell-depleted bone marrow. Progenitor cell recovery, before and after T cell depletion, was monitored using granulocyte-macrophage colony-forming cell assays (GMCFU) and CD34 analysis. The numbers of GMCFU/kg transplanted correlated with engraftment and survival post-transplant and monitoring CD34+ cell numbers in the T cell-depleted marrow pretransplant may be an additional indicator of successful engraftment. Use of a buffy coat marrow preparation with restriction of the number of T cells to < 5 x 10(5)/kg was associated with graft failure in four and death in five of eight children, probably because too few stem cells were infused. T cell depletion of a mononuclear cell preparation of donor marrow with no arbitrary ceiling of infused T cells is highly effective at preventing clinically important GVHD and cured nine out of 10 children transplanted with such material.

摘要

骨髓移植是重症联合免疫缺陷(SCID)患儿唯一的治愈性治疗方法。在没有 HLA 匹配同胞供者的情况下,可以使用单倍体相合的亲代供者骨髓,前提是对其进行 T 细胞清除以预防不可避免的移植物抗宿主病(GVHD)。Campath 1M 已在多个中心成功用于此程序。在我们中心,17 例 SCID 患者加 1 例联合免疫缺陷(CID)患者接受了 Campath 1M 清除 T 细胞的骨髓移植。使用粒细胞-巨噬细胞集落形成细胞测定(GMCFU)和 CD34 分析监测 T 细胞清除前后祖细胞的恢复情况。每千克移植的 GMCFU 数量与移植后的植入和生存相关,移植前监测清除 T 细胞的骨髓中 CD34+细胞数量可能是植入成功的另一个指标。使用血沉棕黄层骨髓制剂,将 T 细胞数量限制在<5×10(5)/kg,8 名儿童中有 4 名出现移植失败,5 名死亡,可能是因为注入的干细胞太少。对供者骨髓的单个核细胞制剂进行 T 细胞清除,且对注入的 T 细胞数量没有任意上限,在预防具有临床重要性的 GVHD 方面非常有效,10 名接受此类材料移植的儿童中有 9 名治愈。

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In vitro T cell depletion using Campath 1M for mismatched BMT for severe combined immunodeficiency (SCID).使用Campath 1M进行体外T细胞清除,用于治疗重症联合免疫缺陷(SCID)的不匹配骨髓移植。
Bone Marrow Transplant. 1997 Feb;19(4):323-9. doi: 10.1038/sj.bmt.1700669.
2
Long-term outcomes of nonconditioned patients with severe combined immunodeficiency transplanted with HLA-identical or haploidentical bone marrow depleted of T cells with anti-CD6 mAb.使用抗CD6单克隆抗体清除T细胞的HLA相同或单倍体相合骨髓移植的非预处理重症联合免疫缺陷患者的长期预后
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Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.在患有致命遗传性疾病(不包括严重联合免疫缺陷)的儿童中,采用来自基因上HLA不匹配供体的骨髓移植:使用两种单克隆抗体预防移植物排斥反应。
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T cell depleted haploidentical bone marrow transplantation for the treatment of children with severe combined immunodeficiency.去除T细胞的单倍体相合骨髓移植治疗重症联合免疫缺陷患儿
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CD6+ T cell depleted allogeneic bone marrow transplantation from genotypically HLA nonidentical related donors.来自基因分型 HLA 不相同的相关供体的 CD6+ T 细胞耗竭的异基因骨髓移植。
Biol Blood Marrow Transplant. 1997 Apr;3(1):11-7.
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Haploidentical peripheral blood stem cell transplantation with a combination of CD34 selection and T cell depletion as graft-versus-host disease prophylaxis in a patient with severe combined immunodeficiency.
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Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency.造血干细胞移植治疗重症联合免疫缺陷病。
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Control of graft-versus-host disease and graft rejection by T cell depletion of donor and recipient with Campath-1 antibodies. Results of matched sibling transplants for malignant diseases.使用Campath-1抗体对供体和受体进行T细胞清除以控制移植物抗宿主病和移植排斥反应。恶性疾病同胞匹配移植的结果。
Bone Marrow Transplant. 1994 May;13(5):597-611.

引用本文的文献

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A trial of alemtuzumab adjunctive therapy in allogeneic hematopoietic cell transplantation with minimal conditioning for severe combined immunodeficiency.阿仑单抗辅助治疗用于严重联合免疫缺陷的低强度预处理异基因造血细胞移植的试验。
Pediatr Transplant. 2014 Sep;18(6):609-16. doi: 10.1111/petr.12310. Epub 2014 Jun 30.
2
Outcomes of patients with severe combined immunodeficiency treated with hematopoietic stem cell transplantation with and without preconditioning.接受和未接受预处理的造血干细胞移植治疗的重症联合免疫缺陷患者的结局。
J Allergy Clin Immunol. 2009 Nov;124(5):1062-9.e1-4. doi: 10.1016/j.jaci.2009.08.041.
3
Umbilical cord blood transplantation in severe T-cell immunodeficiency disorders: two-year experience.
严重T细胞免疫缺陷疾病中的脐带血移植:两年经验
J Clin Immunol. 2000 Nov;20(6):466-76. doi: 10.1023/a:1026463900925.
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Clinical course of patients with major histocompatibility complex class II deficiency.主要组织相容性复合体II类缺陷患者的临床病程。
Arch Dis Child. 2000 Oct;83(4):356-9. doi: 10.1136/adc.83.4.356.