Wysoczanska B, Bogunia-Kubik K, Dlubek D, Jaskula E, Sok A, Drabczak-Skrzypek D, Sedzimirska M, Lange A
L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Transplant Proc. 2007 Nov;39(9):2898-901. doi: 10.1016/j.transproceed.2007.08.036.
INTRODUCTION: Allotransplantation in chronic myeloid leukemia (CML) patients offers long-lasting remissions, which largely depend on immunologic surveillance of alloreactivity. Alloreactivity in CML patients has a durable potential. However a large proportion of relapsing patients, who have to undergo donor lymphocyte treatment is still abundant. METHODS: We studied a group of 31 CML patients post allogeneic transplantation for their level of T-cell receptor excision circles (TREC) and proportion of naive and memory/effector T cells in the peripheral blood (PB). TREC numbers were determined by quantitative PCR (qPCR) and T-cell subsets CD4(+)CD27(+)CD45RO(-), CD4(+)CD27(-)CD24RO(+), CD4(+)CCR7(+), and CD4(+)CCR7(-) by flow cytometry. Patients were analyzed for posttransplant chimerism, type of bcr-abl transcripts, and number of TREC in association with the presence of chronic graft-versus-host disease (cGVHD) and relapse. CML patients with TREC+ in PB had a higher proportion of CD4(+)CD27(+)CD45RO(-) cells (3.54 vs 2.45%; P = .105) and CD4(+)CCR7(+) cells (4.85 vs 2.67%; P = .007), and a lower proportion of CD4(+)CD27(-)CD45RO(+) cells (5.55 vs 9.09%; P = .037). The incidence of cGvHD was reduced among TREC+ CML patients (3/14 vs 11/17; P = .006). RESULTS: The 5 out of 31 CML patients who relapsed were characterized by the presence of b2a2, b3/a2 or both type of transcripts, a lack of TREC in the blood, and a lower proportion of naïve and effector/memory T cells. No association was observed between any of HLA specificities, type of bcr-abl transcripts and incidence of relapse. CONCLUSION: The presence of TREC is affected by chronic GvHD; TREC negativity may constitute a risk of mixed chimerism and relapse.
引言：慢性髓性白血病（CML）患者的同种异体移植可带来持久缓解，这在很大程度上依赖于同种异体反应性的免疫监测。CML患者的同种异体反应性具有持久潜力。然而，仍有很大比例的复发患者需要接受供体淋巴细胞治疗。 方法：我们研究了一组31例接受异基因移植后的CML患者，检测他们外周血（PB）中T细胞受体切除环（TREC）水平以及初始T细胞和记忆/效应T细胞的比例。通过定量聚合酶链反应（qPCR）测定TREC数量，通过流式细胞术检测T细胞亚群CD4(+)CD27(+)CD45RO(-)、CD4(+)CD27(-)CD45RO(+)、CD4(+)CCR7(+)和CD4(+)CCR7(-)。分析患者移植后的嵌合状态、bcr-abl转录本类型以及与慢性移植物抗宿主病（cGVHD）和复发相关的TREC数量。外周血中TREC阳性的CML患者，其CD4(+)CD27(+)CD45RO(-)细胞比例较高（3.54%对2.45%；P = 0.105），CD4(+)CCR7(+)细胞比例较高（4.85%对2.67%；P = 0.007），而CD4(+)CD27(-)CD45RO(+)细胞比例较低（5.55%对9.09%；P = 0.037）。TREC阳性的CML患者中cGvHD的发生率降低（3/14对11/17；P = 0.006）。 结果：31例CML患者中有5例复发，其特征为存在b2a2、b3/a2或两种转录本类型，血液中缺乏TREC，且初始T细胞和效应/记忆T细胞比例较低。未观察到任何HLA特异性、bcr-abl转录本类型与复发率之间存在关联。 结论：TREC的存在受慢性移植物抗宿主病影响；TREC阴性可能构成混合嵌合和复发的风险。
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