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部分匹配相关供体骨髓移植后,急性白血病患者γδT细胞增多并康复后的长期无病生存情况。

Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation.

作者信息

Godder K T, Henslee-Downey P J, Mehta J, Park B S, Chiang K-Y, Abhyankar S, Lamb L S

机构信息

South Carolina Cancer Center, Columbia, SC, USA.

出版信息

Bone Marrow Transplant. 2007 Jun;39(12):751-7. doi: 10.1038/sj.bmt.1705650. Epub 2007 Apr 23.

Abstract

Allogeneic stem cell transplantation (ASCT) has improved leukemia-free survival (LFS) in many but not all patients with acute leukemia. This is an eight-year follow-up to our previous study showing a survival advantage to patients with an increased gammadelta T cells following ASCT. gammadelta T cell levels were collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n = 77; acute myelogenous leukemia (AML) n = 76) undergoing partially mismatched related donor ASCT. Median age was 22 years (1-59), and 62% of the patients were in relapse at transplant. Patient-donor human leukocyte antigen (HLA) disparity of three antigens was 37% in the graft-versus-host disease (GvHD) and 29% in the rejection directions. All patients received a partially T cell-depleted graft using T10B9 (n = 46) or OKT3 (n = 107). Five years LFS and overall survival (OS) of patients with increased gammadelta compared to those with normal/decreased numbers were 54.4 vs 19.1%; P < 0.0003, and 70.8 vs 19.6% P < 0.0001, respectively, with no difference in GvHD (P = 0.96). In a Cox multivariate analysis, normal/decreased gammadelta (hazard ratio (HR) 4.26, P = 0.0002) and sex mismatch (HR 1.45 P=0.049) were associated with inferior LFS. In conclusion, gammadelta T cells may facilitate a graft-versus-leukemia (GvL) effect, without causing GvHD. Further evaluations of this effect may lead to specific immunotherapy for patients with refractory leukemia.

摘要

异基因干细胞移植(ASCT)改善了许多(但并非所有)急性白血病患者的无白血病生存期(LFS)。这是对我们之前研究的八年随访,该研究表明ASCT后γδT细胞增加的患者具有生存优势。前瞻性收集了153例接受部分不匹配相关供体ASCT的患者(急性淋巴细胞白血病(ALL)n = 77;急性髓性白血病(AML)n = 76)的γδT细胞水平。中位年龄为22岁(1 - 59岁),62%的患者在移植时处于复发状态。移植物抗宿主病(GvHD)方向的患者 - 供体人类白细胞抗原(HLA)三个抗原不匹配率为37%,排斥方向为29%。所有患者均使用T10B9(n = 46)或OKT3(n = 107)接受部分T细胞去除的移植物。与γδT细胞数量正常/减少的患者相比,γδT细胞增加的患者的五年LFS和总生存期(OS)分别为54.4%对19.1%;P < 0.0003,以及70.8%对19.6%,P < 0.0001,GvHD无差异(P = 0.96)。在Cox多变量分析中,γδT细胞数量正常/减少(风险比(HR)4.26,P = 0.0002)和性别不匹配(HR 1.45,P = 0.049)与较差的LFS相关。总之,γδT细胞可能促进移植物抗白血病(GvL)效应,而不引起GvHD。对这种效应的进一步评估可能会为难治性白血病患者带来特异性免疫疗法。

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