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异基因干细胞移植的最新进展

Recent progress in allogeneic stem cell transplantation.

作者信息

Mattsson Jonas

机构信息

Karolinska Institutet, Karolinska University Hospital, Center for Allogeneic Stem Cell Transplantation, Huddinge, SE-141 86 Stockholm, Sweden.

出版信息

Curr Opin Mol Ther. 2008 Aug;10(4):343-9.

PMID:18683098
Abstract

Allogeneic hematopoietic stem cell transplantation (ASCT) is a well-established treatment for patients with malignant and non-malignant immunohematopoietic diseases. Matched unrelated donors are increasingly used and improved HLA matching has led to increased survival. In addition, stem cells derived from peripheral blood and cord blood are being utilized to a greater extent. During the last decade, reduced-intensity conditioning, which is preferentially used in older patients or those with organ dysfunction, was introduced as an alternative to standard myeloablative regimens. In addition, the isolation of patients after transplant has been challenged by allowing patients to be treated at home after ASCT. Analysis of mutations in caspase recruitment domain containing protein 15 and levels of regulatory T-cells may be important in identifying patients at risk for acute graft-versus-host disease (GVHD). Mesenchymal stem cells that have immunomodulatory effects home in to injured tissues and may be used in the treatment of patients with steroid-refractory GVHD. In addition, the graft-versus-tumor (GVT) or graft-versus-leukemia (GVL) effect (ie, the attack of the transplanted immune system against the tumor or leukemia), is of major importance for the success of ASCT in patients with malignant disease. GVT and GVL effects may be improved by utilizing differences in minor histocompatibility antigens between the patients and the donor or by using natural killer cell alloreactivity. ASCT has shown GVT effects in patients with solid tumors. New developments in clinical ASCT have been highlighted in this review.

摘要

异基因造血干细胞移植(ASCT)是治疗恶性和非恶性免疫血液系统疾病患者的一种成熟疗法。越来越多地使用匹配的无关供体,改进的HLA配型提高了生存率。此外,外周血和脐带血来源的干细胞得到了更广泛的应用。在过去十年中,引入了强度降低的预处理方案,优先用于老年患者或有器官功能障碍的患者,作为标准清髓方案的替代方案。此外,允许患者在ASCT后在家中接受治疗,对移植后患者的隔离提出了挑战。分析含半胱天冬酶募集结构域蛋白15的突变和调节性T细胞水平,对于识别有急性移植物抗宿主病(GVHD)风险的患者可能很重要。具有免疫调节作用的间充质干细胞归巢至受损组织,可用于治疗对类固醇难治的GVHD患者。此外,移植物抗肿瘤(GVT)或移植物抗白血病(GVL)效应(即移植的免疫系统对肿瘤或白血病的攻击),对于恶性疾病患者ASCT的成功至关重要。利用患者与供体之间次要组织相容性抗原的差异或使用自然杀伤细胞同种异体反应性,可改善GVT和GVL效应。ASCT已在实体瘤患者中显示出GVT效应。本综述重点介绍了临床ASCT的新进展。

相似文献

1
Recent progress in allogeneic stem cell transplantation.异基因干细胞移植的最新进展
Curr Opin Mol Ther. 2008 Aug;10(4):343-9.
2
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。
Dan Med Bull. 2007 May;54(2):112-39.
3
Immunotherapy by allogeneic stem cell transplantation.异基因干细胞移植免疫疗法。
Adv Cancer Res. 2007;97:25-60. doi: 10.1016/S0065-230X(06)97002-X.
4
Reduced-intensity conditioning for the treatment of malignant and life-threatening non-malignant disorders.降低强度预处理用于治疗恶性和危及生命的非恶性疾病。
Clin Transpl. 2003:275-82.
5
Allogeneic hematopoietic stem cell transplantation: state of the art and new perspectives.异基因造血干细胞移植:现状与新展望。
APMIS. 2005 Nov-Dec;113(11-12):813-30. doi: 10.1111/j.1600-0463.2005.apm_336.x.
6
Reduced-intensity allogeneic stem cell transplantation in adults and children with malignant and nonmalignant diseases: end of the beginning and future challenges.成人和儿童恶性及非恶性疾病的减低强度异基因干细胞移植:开端的结束与未来挑战
Biol Blood Marrow Transplant. 2005 Jun;11(6):403-22. doi: 10.1016/j.bbmt.2005.04.002.
7
The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement?同种异体骨髓/干细胞移植的抗肿瘤作用,无移植物抗宿主病毒性且无需匹配供体?
Med Hypotheses. 2008;70(6):1186-92. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.
8
Differential requirement for a cellular type-1 immune response in tumor-associated versus alloantigen-targeted GvT effects.肿瘤相关与同种异体抗原靶向移植物抗肿瘤效应中细胞1型免疫反应的差异需求。
Transplantation. 2007 Feb 15;83(3):314-22. doi: 10.1097/01.tp.0000250725.95074.f1.
9
[Minor antigens - major impact. The role of minor histocompatibility antigens in allogeneic hematopoietic stem cell transplantation].[次要抗原——重大影响。次要组织相容性抗原在异基因造血干细胞移植中的作用]
Dtsch Med Wochenschr. 2008 Jul;133(28-29):1511-6. doi: 10.1055/s-2008-1081100.
10
Allogeneic stem cell transplantation after reduced-intensity conditioning for acute myeloid leukaemia: impact of chronic graft-versus-host disease.急性髓系白血病减低强度预处理后的异基因干细胞移植:慢性移植物抗宿主病的影响
Curr Opin Oncol. 2009 Jun;21 Suppl 1:S35-7. doi: 10.1097/01.cco.0000357474.66035.9b.

引用本文的文献

1
Flt3L Treatment of Bone Marrow Donors Increases Graft Plasmacytoid Dendritic Cell Content and Improves Allogeneic Transplantation Outcomes.Flt3L 治疗骨髓供者可增加移植物浆细胞样树突状细胞含量并改善同种异体移植结局。
Biol Blood Marrow Transplant. 2019 Jun;25(6):1075-1084. doi: 10.1016/j.bbmt.2018.11.029. Epub 2018 Nov 29.
2
Long-lasting effects of human mesenchymal stem cell systemic administration on pain-like behaviors, cellular, and biomolecular modifications in neuropathic mice.人骨髓间充质干细胞系统给药对神经病理性疼痛样行为、细胞和生物分子改变的长期影响。
Front Integr Neurosci. 2011 Dec 1;5:79. doi: 10.3389/fnint.2011.00079. eCollection 2011.
3
C-reactive protein levels before reduced-intensity conditioning predict outcome after allogeneic stem cell transplantation.
在接受减强度预处理条件后,C 反应蛋白水平可预测异基因干细胞移植后的结果。
Int J Hematol. 2010 Jul;92(1):161-7. doi: 10.1007/s12185-010-0632-7. Epub 2010 Jun 25.
4
Intra-brain microinjection of human mesenchymal stem cells decreases allodynia in neuropathic mice.脑内微量注射人骨髓间充质干细胞可减轻神经病理性痛小鼠的痛觉过敏。
Cell Mol Life Sci. 2010 Feb;67(4):655-69. doi: 10.1007/s00018-009-0202-4. Epub 2009 Nov 24.