Hematology and Stem Cell Transplantation Section, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Biol Blood Marrow Transplant. 2012 Jul;18(7):1069-75. doi: 10.1016/j.bbmt.2011.12.518. Epub 2011 Dec 13.
Relapse remains a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). Graft-versus-tumor effect is primarily mediated by donor T cells. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a critical inhibitor of T cell proliferation. Single nucleotide polymorphisms (SNPs) in CTLA-4 may affect immune responses. We hypothesized that CTLA-4 SNPs will be associated with disease control after allo-HCT. One hundred sixty-four adult patients with the availability of pretransplantation recipient and donor DNA samples were included in this analysis. Ten tagSNPs of the CTLA-4 gene were identified. Donor CTLA-4 SNP rs4553808 was associated with decreased relapse-free survival (RFS) (P = .019) and overall survival (OS) (P = .033). In multivariable analysis of an additive genetic model, genotype of CTLA-4 SNP rs4553808 was an independent risk factor for inferior RFS (hazard ratio [HR] = 1.73, 95% confidence interval [CI] 1.10-2.71, P = .017) and OS (HR = 1.84, 95% CI 1.13-3.0, P = .015). CTLA-4 SNPs can be used to identify high-risk patient subsets that may benefit from preemptive immunomodulation to decrease relapse rates and improve survival.
在异基因造血细胞移植（allo-HCT）后，复发仍然是主要的死亡原因。移植物抗肿瘤效应主要由供体 T 细胞介导。细胞毒性 T 淋巴细胞抗原-4（CTLA-4）是 T 细胞增殖的关键抑制剂。CTLA-4 中的单核苷酸多态性（SNPs）可能影响免疫反应。我们假设 CTLA-4 SNPs 与 allo-HCT 后的疾病控制有关。本分析纳入了 164 例成年患者，这些患者均有移植前供体和受者 DNA 样本。鉴定了 CTLA-4 基因的 10 个标签 SNP。供体 CTLA-4 SNP rs4553808 与无复发生存率（RFS）（P =.019）和总生存率（OS）（P =.033）降低相关。在 CTLA-4 SNP rs4553808 的加性遗传模型的多变量分析中，基因型是 RFS 较差的独立危险因素（危险比[HR] = 1.73，95%置信区间[CI] 1.10-2.71，P =.017）和 OS（HR = 1.84，95% CI 1.13-3.0，P =.015）。CTLA-4 SNPs 可用于识别高危患者亚组，这些患者可能受益于抢先免疫调节以降低复发率并提高生存率。
