Department of Pediatrics, Jena University Hospital, Jena, Germany.
Department of Internal Medicine Il, Jena University Hospital, Jena, Germany.
Eur J Haematol. 2019 Mar;102(3):251-255. doi: 10.1111/ejh.13200. Epub 2019 Jan 7.
Relapse following allogeneic hematopoietic stem cell transplantation (HSCT) is still linked to a poor prognosis. Mainly, donor`s T-cells mediate the graft-versus-leukemia effect. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule which down-regulates T-cell activation. Single nucleotide polymorphism (SNP) in CTLA-4 may have an effect on immune response.
Eighty-eight children with acute leukemia and their donors were genotyped of CTLA-4 gene for rs231775. We searched for an association of CTLA-4 SNP with relapse and survival after allogeneic HSCT.
We identified a significantly reduced relapse rate in children who received a transplant from a donor with the CTLA-4 genotypes AG or GG in comparison with genotype AA of rs231775 (19% vs 40%, P = 0.026). In addition, we observed a significant difference in event-free survival (EFS) depending on the donor´s genotype. The EFS was 70% or 46% if the patient was transplanted from a donor with CTLA-4 genotype AG/GG or AA, respectively (P = 0.025). In multivariate analysis, CTLA-4 genotype was an independent risk factor for relapse rate (P = 0.028).
This study suggests that CTLA-4 polymorphism rs231775 is relevant for relapse and survival after allogeneic HSCT in childhood and should be further investigated in clinical trials.
异基因造血干细胞移植（HSCT）后复发仍然与预后不良有关。主要是供体 T 细胞介导移植物抗白血病效应。细胞毒性 T 淋巴细胞抗原-4（CTLA-4）是一种抑制分子，可下调 T 细胞激活。CTLA-4 中的单核苷酸多态性（SNP）可能对免疫反应有影响。
对 88 例急性白血病患儿及其供者进行 CTLA-4 基因 rs231775 的单核苷酸多态性检测。我们探讨了 CTLA-4 SNP 与异基因 HSCT 后复发和生存的关系。
与 rs231775 的 CTLA-4 基因型 AA 相比，接受供体 CTLA-4 基因型 AG 或 GG 移植的患儿复发率明显降低（19% vs 40%，P=0.026）。此外，我们观察到供体基因型对无事件生存（EFS）有显著影响。如果患者从 CTLA-4 基因型 AG/GG 或 AA 的供体接受移植，则 EFS 分别为 70%或 46%（P=0.025）。多变量分析显示，CTLA-4 基因型是复发率的独立危险因素（P=0.028）。
本研究表明，CTLA-4 多态性 rs231775 与儿童异基因 HSCT 后复发和生存相关，应在临床试验中进一步研究。
