Altered effect of killer immunoglobulin-like receptor-ligand mismatch by graft versus host disease prophylaxis in cord blood transplantation
Altered effect of killer immunoglobulin-like receptor-ligand mismatch by graft versus host disease prophylaxis in cord blood transplantation
复制标题
脐带血移植中移植物抗宿主病预防改变杀伤性免疫球蛋白样受体配体错配的效果
DOI：
10.1038/s41409-021-01469-6
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Morishima
中科院分区：
文献类型：
--
作者：
Yokoyama H;Hirayama M;Takahashi Y;Uchida N;Tanaka M;Onizuka M;Ozawa Y;Onai D;Katsuoka Y;Wake A;Sawa M;Kobayashi H;Maruyama Y;Ozeki K;Kimura T;Kanda J;Fukuda T;Atsuta Y;Terakura S;Morishima
接受脐带血移植 (CBT) 的供者和受者之间杀伤性免疫球蛋白样受体配体错配（KIR-配体错配）的作用存在争议。如果每种免疫抑制剂对自然杀伤 (NK) 细胞功能的影响不同，则 KIR-配体错配的效果可能会根据移植物抗宿主病 (GVHD) 预防的类型而改变。为了验证这一假设，我们回顾性评估了接受 CBT 治疗急性白血病、骨髓增生异常综合征或慢性粒细胞白血病的患者以及接受他克莫司加甲氨蝶呤 (MTX) 或霉酚酸酯 (MMF) 预防 GVHD 的患者之间 KIR 配体错配效果的差异。在MMF组（n= 1363）中，KIR-配体错配增加了非复发死亡率的发生率（NRM；风险比[HR]，1.40；P= 0.008），从而恶化了总生存期（OS；HR，1.30，P= 0.0077）。在对每种 KIR-配体错配类型的分析中，HLA-C2 错配仅对 MTX 组的复发率（HR，0.56；P= 0.0043）和 OS（HR，0.72；P= 0.037）有有利影响。在MMF组中，HLA-A3/A11不匹配使NRM（HR，1.93；P< 0.001）和OS（HR，1.48；P= 0.014）恶化。这些结果意味着 KIR-配体错配的影响因 GVHD 预防类型的不同而不同，并且评估 KIR-配体错配状态对于 CBT 很重要。
The role of killer immunoglobulin-like receptor–ligand mismatch (KIR–ligand mismatch) between donors and recipients undergoing cord blood transplantation (CBT) is controversial. If each immunosuppressant differently affects natural killer (NK) cell function, the effect of KIR–ligand mismatch may be altered depending on the type of graft versus host disease (GVHD) prophylaxis. To verify this hypothesis, the difference in the effect of KIR–ligand mismatch was retrospectively assessed between patients who received CBT for acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia, as well as GVHD prophylaxis comprising tacrolimus plus methotrexate (MTX) or mycophenolate mofetil (MMF). In the MMF group (n= 1363), KIR–ligand mismatch augmented the incidence of non-relapse mortality (NRM; hazard ratio [HR], 1.40;P= 0.008), which worsened overall survival (OS; HR, 1.30,P= 0.0077). In the analysis of each KIR–ligand mismatch type, HLA-C2 mismatch had a favorable effect on relapse incidence (HR, 0.56;P= 0.0043) and OS (HR, 0.72;P= 0.037) only in the MTX group. In the MMF group, HLA-A3/A11 mismatch worsened NRM (HR, 1.93;P< 0.001) and OS (HR, 1.48;P= 0.014). These results imply that the effects of KIR–ligand mismatch differ with the type of GVHD prophylaxis and that assessing the KIR–ligand mismatch status is important for CBT.