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非清髓性变应性造血干细胞移植后早期急性和慢性白血病患者Wilms 瘤抗原 1 特异性 T 淋巴细胞的生成比较。

Comparison of Wilms' tumor antigen 1-specific T lymphocyte generation soon after nonmyeloablative allergenic stem-cell transplantation in acute and chronic leukemia patients.

机构信息

Department of Hematology, Affiliated Hospital of Academy of Military Medicine Science, Beijing, China.

出版信息

Int J Hematol. 2010 May;91(4):652-60. doi: 10.1007/s12185-010-0551-7. Epub 2010 Apr 8.

DOI:10.1007/s12185-010-0551-7
PMID:20376582
Abstract

Clinical studies have shown that NST has better therapeutic results with chronic myelogenous leukemia (CML) than acute leukemia (AL), but whether the generation of graft-versus-leukemia (GVL) effects is different between AL and CML patients early after NST has not yet been studied, so we used a pentamer-staining technique in combination with ICCS to detect WT1(+)CD8(+)CTL/WT1(+)Tc1 and WT1(+)Th1 cells in these two groups of patients. Results showed that the emergence time of WT1(+)CD(8) (+)CTL/WT1(+)Tc1 cells after NST in AL patients was similar to that in CML patients (P = 0.58), while the emergence time of WT1(+)Th1 cells after NST in AL patients was shorter than in CML patients (P = 0.047). Furthermore, the peak proportions of WT1(+)CD(8) (+)CTL/WT1(+)Tc1 (P > 0.05) and WT1(+)Th1 (P > 0.05) cells were similar between AL and CML patients, and the increased rates (P > 0.05) and elevated levels (P > 0.05) of WT1-specific T cells were not statistically different between the groups after G-CSF mobilized donor mononuclear cell infusion. In addition, the reconstruction of lymphocyte subsets (P > 0.05) and CD4/8 ratios (P > 0.05) in AL patients were not statistically different from those in CML patients within 180 days after NST. These results suggested that WT1 maybe induces similar GVL effects in both AL and CML patients early after NST.

摘要

临床研究表明,NST 治疗慢性髓性白血病(CML)比治疗急性白血病(AL)的疗效更好,但 NST 后早期 AL 和 CML 患者产生移植物抗白血病(GVL)效应是否不同,尚未进行研究,因此我们使用五聚体染色技术结合 ICCS 检测这两组患者中的 WT1(+)CD8(+)CTL/WT1(+)Tc1 和 WT1(+)Th1 细胞。结果表明,AL 患者 NST 后 WT1(+)CD(8) (+)CTL/WT1(+)Tc1 细胞的出现时间与 CML 患者相似(P = 0.58),而 AL 患者 NST 后 WT1(+)Th1 细胞的出现时间早于 CML 患者(P = 0.047)。此外,AL 和 CML 患者 NST 后 WT1(+)CD(8) (+)CTL/WT1(+)Tc1(P > 0.05)和 WT1(+)Th1(P > 0.05)细胞的峰值比例相似,G-CSF 动员供者单个核细胞输注后两组 WT1 特异性 T 细胞的增加率(P > 0.05)和升高水平(P > 0.05)无统计学差异。此外,NST 后 180 天内,AL 患者淋巴细胞亚群(P > 0.05)和 CD4/8 比值(P > 0.05)的重建与 CML 患者无统计学差异。这些结果表明,WT1 可能在 NST 后早期诱导 AL 和 CML 患者产生相似的 GVL 效应。

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本文引用的文献

1
Comparison of myeloablative and nonmyeloablative hematopoietic stem cell transplantation for treatment of chronic myeloid leukemia.清髓性与非清髓性造血干细胞移植治疗慢性髓性白血病的比较
Int J Hematol. 2007 Oct;86(3):275-81. doi: 10.1532/IJH97.A10701.
2
Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia.急性淋巴细胞白血病异基因干细胞移植后,与可检测到的肾母细胞瘤-1特异性T淋巴细胞相关的移植物抗白血病效应。
Blood. 2007 Sep 15;110(6):1924-32. doi: 10.1182/blood-2007-03-076844. Epub 2007 May 15.
3
The impact of chimerism patterns and predonor leukocyte infusion lymphopenia on survival following T cell-depleted reduced intensity conditioned transplants.
嵌合模式和供者淋巴细胞输注前淋巴细胞减少对T细胞去除的减低剂量预处理移植后生存的影响。
Biol Blood Marrow Transplant. 2007 May;13(5):550-9. doi: 10.1016/j.bbmt.2006.12.451. Epub 2007 Feb 15.
4
Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation.供体淋巴细胞输注用于治疗HLA不匹配/单倍体相合、T细胞充足的造血干细胞移植后白血病复发。
Haematologica. 2007 Mar;92(3):414-7. doi: 10.3324/haematol.10570.
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Identification of a highly immunogenic HLA-A*01-binding T cell epitope of WT1.WT1高度免疫原性HLA-A*01结合T细胞表位的鉴定。
Clin Cancer Res. 2006 Dec 15;12(24):7476-82. doi: 10.1158/1078-0432.CCR-06-1337.
6
T-cell responses directed against multiple HLA-A*0201-restricted epitopes derived from Wilms' tumor 1 protein in patients with leukemia and healthy donors: identification, quantification, and characterization.白血病患者和健康供体中针对源自肾母细胞瘤1蛋白的多个HLA-A*0201限制性表位的T细胞反应:鉴定、定量和表征。
Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8799-807. doi: 10.1158/1078-0432.CCR-05-1314.
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