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双脐血移植后长期混合供者-供者嵌合体的特征。

Characterization of long-term mixed donor-donor chimerism after double cord blood transplantation.

机构信息

Centre for Allogeneic Stem Cell Transplantation and Division of Clinical Immunology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Clin Exp Immunol. 2010 Oct;162(1):146-55. doi: 10.1111/j.1365-2249.2010.04212.x. Epub 2010 Aug 20.

DOI:10.1111/j.1365-2249.2010.04212.x
PMID:20731674
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2990940/
Abstract

Double cord blood transplantation (DCBT) with two matched or partially matched cord blood units has been implemented successfully to circumvent the limitations of graft cell dose associated with single CBT. After DCBT, sustained haematopoiesis is derived almost exclusively from only one of the donated units. None the less, we previously observed two of six evaluable DCBT patients still having mixed donor-donor chimerism at 28 and 45 months post-transplantation, respectively. In the present study we utilize flow cytometry techniques to perform the first thorough analysis of phenotype and functionality of cord blood units in patients with mixed donor-donor chimerism. Our results suggest that the two stable cord blood units are different phenotypically and functionally: one unit shows more naive T cells, lower T cell cytokine production and higher frequencies of natural killer cells, the other shows higher frequencies of well-differentiated and functional lymphocytes. Additionally, in comparison with control patients having a single prevailing cord blood unit, the patients with donor-donor chimerism exhibit less overall T cell cytokine production and a smaller fraction of memory T cells. Furthermore, our results indicate that human leucocyte antigen-C match of donor units may partly explain the development of a donor-donor mixed chimerism.

摘要

双份脐带血移植(DCBT)采用两个匹配或部分匹配的脐带血单位,成功地规避了与单个 CBT 相关的移植物细胞剂量的限制。在 DCBT 之后,持续的造血几乎完全来自于捐赠的单位之一。尽管如此,我们之前观察到 6 名可评估的 DCBT 患者中的 2 名,分别在移植后 28 个月和 45 个月时仍存在混合供体-供体嵌合体。在本研究中,我们利用流式细胞术技术对混合供体-供体嵌合体患者的脐带血细胞表型和功能进行了首次全面分析。我们的结果表明,两个稳定的脐带血单位在表型和功能上存在差异:一个单位显示出更多的幼稚 T 细胞、较低的 T 细胞细胞因子产生和较高的自然杀伤细胞频率,另一个单位显示出更高频率的分化良好和功能齐全的淋巴细胞。此外,与具有单个主要脐带血单位的对照患者相比,嵌合体患者的整体 T 细胞细胞因子产生较少,记忆 T 细胞比例较小。此外,我们的结果表明,供体单位的人类白细胞抗原-C 匹配可能部分解释了供体-供体混合嵌合体的发展。

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本文引用的文献

1
Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit.双份脐血单个核细胞移植后出现单个核细胞优势与针对未植入供者的特异性 CD8+ T 细胞反应有关。
Blood. 2010 Jan 28;115(4):757-65. doi: 10.1182/blood-2009-07-228999. Epub 2009 Oct 12.
2
Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units.脐带血移植后的复发风险:2单位移植受者的移植物抗白血病效应增强
Blood. 2009 Nov 5;114(19):4293-9. doi: 10.1182/blood-2009-05-220525. Epub 2009 Aug 25.
3
Stable mixed donor-donor chimerism after double cord blood transplantation.双脐血移植后稳定的混合供者-供者嵌合体。
Int J Hematol. 2009 Nov;90(4):526-531. doi: 10.1007/s12185-009-0398-y. Epub 2009 Aug 22.
4
Type 1 regulatory T cells are associated with persistent split erythroid/lymphoid chimerism after allogeneic hematopoietic stem cell transplantation for thalassemia.1 型调节性 T 细胞与地中海贫血患者异基因造血干细胞移植后持续的红系/淋巴系嵌合体有关。
Haematologica. 2009 Oct;94(10):1415-26. doi: 10.3324/haematol.2008.003129. Epub 2009 Jul 16.
5
[Reconstitution of NK cells and their receptors in patients with acute leukemia following unrelated cord blood stem cell transplantation].[非亲缘脐血干细胞移植后急性白血病患者自然杀伤细胞及其受体的重建]
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Apr;17(2):426-30.
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Single versus double unrelated umbilical cord blood units for allogeneic transplantation in adults with advanced haematological malignancies: a retrospective comparison of outcomes.成人晚期血液恶性肿瘤患者异基因移植中单份与双份无关脐血单位:结局的回顾性比较。
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Leukemia. 2009 Mar;23(3):492-500. doi: 10.1038/leu.2008.365. Epub 2009 Jan 8.
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Clinical impact of natural killer cell reconstitution after allogeneic hematopoietic transplantation.异基因造血移植后自然杀伤细胞重建的临床影响
Semin Immunopathol. 2008 Dec;30(4):489-503. doi: 10.1007/s00281-008-0136-1. Epub 2008 Nov 11.
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Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor.无关脐血移植和不匹配的无关志愿供者移植,是缺乏 HLA 相合同胞供者的患者的两种替代选择。
Bone Marrow Transplant. 2008 Nov;42(10):643-8. doi: 10.1038/bmt.2008.239. Epub 2008 Sep 1.
10
Using reduced intensity conditioning and HLA-identical sibling donors, antithymocyte globulin increases the risk of relapse, which can be overcome by a high stem cell dose.
Bone Marrow Transplant. 2008 Dec;42(11):769-71. doi: 10.1038/bmt.2008.246. Epub 2008 Aug 11.