FRC Blood Service, Research and Development , Helsinki , Finland.
Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere , Tampere , Finland.
Front Immunol. 2014 Aug 25;5:405. doi: 10.3389/fimmu.2014.00405. eCollection 2014.
Successful allogeneic hematopoietic stem cell transplantation (HSCT) depends not only on good HLA match but also on T-cell mediated graft-versus-leukemia (GvL) effect. Natural killer (NK) cells are able to kill malignant cells by receiving activation signal from the killer-cell immunoglobulin-like receptors (KIR) recognizing HLA molecules on a cancer cell. It has been recently reported that the risk of relapse in allogeneic hematopoietic stem cell transplantation (HSCT) is reduced in acute myeloid leukemia (AML) patients whose donors have several activating KIR genes or KIR B-motifs in unrelated donor setting, obviously due to enhanced GvL effect by NK cells. We studied the effect on relapse rate of donor KIR haplotypes in the HLA-identical adult sibling HSCT, done in a single center, in Helsinki University Central Hospital, Helsinki, Finland. Altogether, 134 patients with 6 different diagnoses were identified. Their donors were KIR genotyped using the Luminex and the SSP techniques. The clinical endpoint, that is, occurrence of relapse, was compared with the presence or absence of single KIR genes. Also, time from transplantation to relapse was analyzed. The patients with AML whose donors have KIR2DL2 or KIR2DS2 had statistically significantly longer relapse-free survival (P = 0.015). Our data support previous reports that donors with KIR B-haplotype defining genes have a lower occurrence of relapse in HSCT of AML patients. Determination of donor KIR haplotypes could be a useful addition for a risk assessment of HSCT especially in AML patients.
异基因造血干细胞移植(HSCT)的成功不仅依赖于良好的 HLA 匹配,还依赖于 T 细胞介导的移植物抗白血病(GvL)效应。自然杀伤(NK)细胞能够通过接收来自识别癌细胞上 HLA 分子的杀伤细胞免疫球蛋白样受体(KIR)的激活信号来杀死恶性细胞。最近有报道称,在无关供体情况下,具有多个激活 KIR 基因或 KIR B 基序的供体的急性髓系白血病(AML)患者接受异基因造血干细胞移植(HSCT)的复发风险降低,显然是由于 NK 细胞增强了 GvL 效应。我们研究了在芬兰赫尔辛基大学中心医院进行的 HLA 相同的成人同胞 HSCT 中供体 KIR 单倍型对复发率的影响。总共确定了 134 例具有 6 种不同诊断的患者。使用 Luminex 和 SSP 技术对供体进行了 KIR 基因分型。临床终点,即复发的发生,与单个 KIR 基因的存在或不存在进行了比较。此外,还分析了从移植到复发的时间。供体具有 KIR2DL2 或 KIR2DS2 的 AML 患者的无复发生存时间明显更长(P=0.015)。我们的数据支持先前的报告,即具有 KIR B-单倍型定义基因的供体在 AML 患者 HSCT 中的复发发生率较低。供体 KIR 单倍型的确定可能是 HSCT 风险评估的有用补充,特别是在 AML 患者中。