Sahin Ugur, Dalva Klara, Gungor Funda, Ustun Celalettin, Beksac Meral
Department of Hematology, Cebeci Hospital, Ankara University Faculty of Medicine, 06220, Ankara, Turkey.
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Ann Hematol. 2018 Jun;97(6):1027-1039. doi: 10.1007/s00277-018-3274-0. Epub 2018 Mar 16.
Impact of donor-recipient killer immunoglobulin-like receptor (KIR) gene-gene matching on transplant outcomes is still inconclusive. Recent data suggest that killer cell immunoglobulin-like receptor (KIR) regulated natural killer cell (NK cell) activity may contribute to graft versus leukemia (GvL) effects and graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case-control study aims to evaluate the effects of both aKIR and iKIR donor-recipient genotype matching on the outcomes of T cell replete HLA-identical sibling allo-HSCTs in a homogenous young patient population with myeloid leukemias. Five transplant outcomes including relapse rate (RR), disease-free survival (DFS), overall survival (OS), cumulative incidences of acute GvHD (aGvHD), and chronic GvHD (cGvHD) are investigated. Out of 96 HLA-identical sibling donor-recipient pairs, 34 were matched for activating KIR (aKIR), 38 for inhibitory KIR (iKIR), and 20 for both aKIR and iKIR. Fourty-four pairs were mismatched for both iKIR and aKIR. In univariate analysis, aKIR-matching resulted with a decrease in relapse rate (RR) (hazard ratio [HR]: 0.4; p = 0.04) and an increase in disease-free survival (DFS) (HR: 0.5; p = 0.03). In addition, cGvHD ocurred less frequently in the aKIR-matched (odds ratio [OR]: 0.4; p = 0.04) or iKIR-matched (OR: 0.3; p = 0.009) cohorts. Matching for both aKIR and iKIR was also associated with a decrease in cGvHD incidence (OR: 0.3; p = 0.02). iKIR-matching had no effects on RR, OS, or DFS. Analysis of donor haplotype effects showed haplotype-BB to have a tendency towards reduced relapse rate (HR: 0.4; p = 0.08) and better OS (HR: 0.4; p = 0.04); haplotype-Bx to increase the incidence of cGvHD (OR: 4.1; p = 0.03). In multivariate analysis, DFS advantage remained significant for aKIR-matching (HR: 0.5; p = 0.04); cGvHD incidence was reduced in the presence of iKIR-match (OR: 0.3; p = 0.02) and increased in the presence of haplotype-AB and -BB donors (OR: 7.9; p = 0.02; OR: 5.1; p = 0.03, respectively). In an attempt to investigate the pathogenesis underlying KIR-matching, we searched for residual NK/T cells on day 0 peripheral blood samples of six additional recipients and noted the presence of CD3 (7.0-91.4 × 10/L) and CD5657 (0.8-12.7 × 10/L) cells. In conclusion, conditioning regimen surviving recipient NK/T cells potentially influenced by KIR-matching may contribute to GvL/GvH reactions.
供体与受体杀伤细胞免疫球蛋白样受体（KIR）基因 - 基因匹配对移植结果的影响仍无定论。最近的数据表明，杀伤细胞免疫球蛋白样受体（KIR）调节的自然杀伤细胞（NK细胞）活性可能有助于异基因造血干细胞移植（allo - HSCT）后的移植物抗白血病（GvL）效应和移植物抗宿主病（GvHD）。本病例对照研究旨在评估激活型KIR（aKIR）和抑制型KIR（iKIR）供体 - 受体基因型匹配对患有髓系白血病的同质年轻患者群体中T细胞充足的HLA相同同胞allo - HSCT结果的影响。研究了五个移植结果，包括复发率（RR）、无病生存期（DFS）、总生存期（OS）、急性移植物抗宿主病（aGvHD）和慢性移植物抗宿主病（cGvHD）的累积发生率。在96对HLA相同的同胞供体 - 受体对中，34对激活型KIR（aKIR）匹配，38对抑制型KIR（iKIR）匹配，20对aKIR和iKIR均匹配。44对iKIR和aKIR均不匹配。在单变量分析中，aKIR匹配导致复发率（RR）降低（风险比[HR]：0.4；p = 0.04）和无病生存期（DFS）增加（HR：0.5；p = 0.03）。此外，cGvHD在aKIR匹配组（优势比[OR]：0.4；p = 0.04）或iKIR匹配组（OR：0.3；p = 0.009）中发生频率较低。aKIR和iKIR均匹配也与cGvHD发生率降低相关（OR：0.3；p = 0.02）。iKIR匹配对RR、OS或DFS无影响。供体单倍型效应分析显示，单倍型 - BB有降低复发率的趋势（HR：0.4；p = 0.08）和更好的OS（HR：0.4；p = 0.04）；单倍型 - Bx增加cGvHD的发生率（OR：4.1；p = 0.03）。在多变量分析中，aKIR匹配的DFS优势仍然显著（HR：0.5；p = 0.04）；iKIR匹配时cGvHD发生率降低（OR：0.3；p = 0.02），而单倍型 - AB和 - BB供体存在时cGvHD发生率增加（分别为OR：7.9；p = 0.02；OR：5.1；p = 0.03）。为了研究KIR匹配潜在的发病机制，我们在另外六名受者的第0天外周血样本中寻找残留的NK/T细胞，并发现存在CD3（7.0 - 91.4×10/L）和CD5657（0.8 - 12.7×10/L）细胞。总之，预处理方案使可能受KIR匹配影响而存活的受者NK/T细胞可能有助于GvL/GvH反应。
