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在接受含有固定少量T细胞的骨髓移植的患者中实现了完全供体T细胞嵌合。

Complete donor T cell chimerism is accomplished in patients transplanted with bone marrow grafts containing a fixed low number of T cells.

作者信息

Verdonck L F, van Blokland W T, Bosboom-Kalsbeek E K, van Heugten H G, Tilanus M G, de Weger R A

机构信息

Department of Haematology, University Hospital Utrecht, The Netherlands.

出版信息

Bone Marrow Transplant. 1996 Aug;18(2):389-95.

PMID:8864451
Abstract

T cell depletion of the bone marrow graft, the most effective method to prevent severe graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), has resulted in approximately three times more relapses of the disease post-transplant than after non-T cell-depleted BMT. It has been hypothesized that this is caused by the development of mixed T cell chimerism, often observed after T cell depleted BMT, whereas non-T cell-depleted BMT generally results in complete donor T cell chimerism. In order to find an approach of T cell depletion which may avoid the high relapse rate but prevent severe GVHD, we gave marrow recipients a partial T cell-depleted marrow graft containing 1 x 10(5) donor T cells/kg recipient's weight. To investigate whether our approach results in complete donor T cell chimerism, we analyzed post-transplant the origin of purified T cells in 56 patients with hematologic malignancies, including 15 patients at the time they relapsed. The T cells were studied for being of host or donor origin by amplification of four loci of variable number of tandem repeats (VNTR) by PCR. From 6 months post-BMT, all 45 patients who could be analyzed in remission (five had died and six had relapsed within 6 months) had T cells that were exclusively of donor origin. Furthermore, the T cells of 15 patients who had relapsed post-BMT were also exclusively of donor origin. Severe GVHD was never observed. Thus, this approach seems to combine the favorable aspects of both T cell-depleted and non-T cell-depleted BMT.

摘要

骨髓移植中去除骨髓移植物中的T细胞是预防异基因骨髓移植(BMT)后严重移植物抗宿主病(GVHD)的最有效方法,但与未去除T细胞的BMT相比,移植后疾病复发率高出约三倍。据推测,这是由于去除T细胞的BMT后常出现的混合T细胞嵌合体的形成,而未去除T细胞的BMT通常会导致完全的供体T细胞嵌合体。为了找到一种既能避免高复发率又能预防严重GVHD的T细胞去除方法,我们给骨髓移植受者移植了部分去除T细胞的骨髓移植物,每千克受者体重含1×10⁵个供体T细胞。为了研究我们的方法是否能导致完全的供体T细胞嵌合体,我们分析了56例血液系统恶性肿瘤患者移植后纯化T细胞的来源,其中15例患者处于复发时。通过PCR扩增四个可变数目串联重复序列(VNTR)位点来研究T细胞是宿主来源还是供体来源。自BMT后6个月起,所有45例可分析的处于缓解期的患者(5例在6个月内死亡,6例在6个月内复发)的T细胞均完全来自供体。此外,15例BMT后复发患者的T细胞也完全来自供体。从未观察到严重的GVHD。因此,这种方法似乎结合了去除T细胞和未去除T细胞的BMT的有利方面。

相似文献

1
Complete donor T cell chimerism is accomplished in patients transplanted with bone marrow grafts containing a fixed low number of T cells.在接受含有固定少量T细胞的骨髓移植的患者中实现了完全供体T细胞嵌合。
Bone Marrow Transplant. 1996 Aug;18(2):389-95.
2
Donor leukocyte infusions for recurrent hematologic malignancies after allogeneic bone marrow transplantation: impact of infused and residual donor T cells.异基因骨髓移植后复发性血液系统恶性肿瘤的供体白细胞输注:输注的和残留的供体T细胞的影响
Bone Marrow Transplant. 1998 Dec;22(11):1057-63. doi: 10.1038/sj.bmt.1701496.
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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。
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Delayed infusion of normal donor cells after MHC-matched bone marrow transplantation provides an antileukemia reaction without graft-versus-host disease.在 MHC 匹配的骨髓移植后延迟输注正常供体细胞可产生抗白血病反应而无移植物抗宿主病。
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Detection of minimal residual disease and persistence of host-type hematopoiesis: a study in 28 patients after sex-mismatched, non-T cell-depleted allogeneic bone marrow transplantation for Philadelphia-chromosome positive chronic myelogenous leukemia.微小残留病的检测及宿主型造血的持续存在:一项针对28例费城染色体阳性慢性髓性白血病患者接受性别不匹配、非T细胞去除的异基因骨髓移植后的研究。
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Prevention of graft-versus-host disease in high risk patients by depletion of CD4+ and reduction of CD8+ lymphocytes in the marrow graft.通过去除骨髓移植物中的CD4+淋巴细胞并减少CD8+淋巴细胞来预防高危患者的移植物抗宿主病。
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Early detection of bone marrow engraftment by amplification of hypervariable DNA regions.通过高变DNA区域扩增早期检测骨髓植入。
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Alloreactivity as therapeutic principle in the treatment of hematologic malignancies. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.异基因反应性作为血液系统恶性肿瘤治疗的治疗原则。非清髓性预处理的异基因造血细胞移植的临床和免疫学方面的研究。
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Allogeneic cell-mediated immunotherapy using donor lymphocytes for prevention of relapse in patients treated with allogeneic bone marrow transplantation for hematological malignancies.使用供体淋巴细胞进行异基因细胞介导的免疫疗法,以预防接受异基因骨髓移植治疗血液系统恶性肿瘤的患者复发。
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引用本文的文献

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Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12.供体来源的干扰素γ是白细胞介素12抑制急性移植物抗宿主病所必需的。
J Clin Invest. 1998 Dec 15;102(12):2126-35. doi: 10.1172/JCI4992.