肿瘤细胞治疗研究
英文原题：Impact of KIR-ligand mismatch on pediatric T-cell acute lymphoblastic leukemia in unrelated cord blood transplantation.
Impact of KIR-ligand mismatch on pediatric T-cell acute lymphoblastic leukemia in unrelated cord blood transplantation.
纳入1999年至2017年间诊断为T-ALL、年龄0至19岁并接受首次UCBT的患者。
目前，异基因造血干细胞移植（allo-HSCT）被认为适用于高危或复发的儿童及青少年T细胞急性淋巴细胞白血病（T-ALL）；然而，其结局并不令人满意。杀伤细胞免疫球蛋白样受体（KIR）是自然杀伤（NK）细胞上的主要受体，在allo-HSCT后的移植物抗白血病效应中发挥重要作用。在allo-HSCT中，当受者缺乏供者KIR配体（移植物抗宿主[GVH]方向上的KIR配体错配）时，供者NK细胞将被激活以对抗受者细胞。GVH方向上的KIR配体错配可改善急性髓系白血病无关脐血移植（UCBT）后的结局，但其在T-ALL中的效果尚不明确。我们评估了GVH方向上KIR配体错配对接受UCBT的儿童及青少年T-ALL患者移植结局的影响。我们使用日本移植与细胞治疗学会的全国性登记数据进行了一项回顾性研究。纳入诊断为T-ALL、年龄0至19岁、并于1999年至2017年间接受首次UCBT的患者。本研究共纳入91例患者。总体而言，23例（25.3%）患者存在GVH方向上的KIR配体错配。UCBT后5年无白血病生存（LFS）率和总生存（OS）率分别为65.8%和69.6%。在多变量分析中，GVH方向上的KIR配体错配与复发率显著降低相关（风险比[HR]，0.19；P = .002），从而导致更好的LFS（HR，0.18；P = .010）和OS（HR，0.26；P = .048），且未增加非复发死亡（NRM；HR，1.90；P = .264）。GVHD的累积发生率在有无KIR配体不合的患者之间没有差异（II-IV级急性GVHD，39.1%对36.8%，P = .648；III-IV级急性GVHD，13.0%对11.8%，P = .857；慢性GVHD，26.1%对22.9%，P = .736）。此外，急性和慢性GVHD与良好的患者结局无关。值得注意的是，在完全缓解状态下接受KIR配体不合UCBT的患者中未观察到复发。在GVH方向上的KIR配体不合改善了接受UCBT的儿童和青少年T-ALL患者的LFS并降低了复发率，且未增加NRM，这一效应并非由GVHD介导。
Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered to be indicated for children and adolescents with high-risk or relapsed T-cell acute lymphoblastic leukemia (T-ALL); however, the outcomes are unsatisfactory. Killer cell immunoglobulin-like receptors (KIRs) are the main receptors on natural killer (NK) cells that play an important role in the graft-versus-leukemia effect after allo-HSCT. In allo-HSCT, when the recipient lacks a donor KIR-ligand (KIR-ligand mismatch in the graft-versus-host [GVH] direction), donor NK cells will be activated against recipient cells. KIR-ligand mismatch in the GVH direction improves outcomes after unrelated cord blood transplantation (UCBT) with acute myeloid leukemia, but the effect in T-ALL is unclear. We evaluated the impact of KIR-ligand mismatch in the GVH direction on the transplantation outcomes of children and adolescents with T-ALL who received UCBT. We conducted a retrospective study using a nationwide registry of the Japanese Society for Transplantation and Cellular Therapy. Patients diagnosed with T-ALL, aged 0 to 19 years, and who underwent first UCBT between 1999 and 2017 were included. A total of 91 patients were included in this study. In all, 23 (25.3%) percent of patients had KIR-ligand mismatch in the GVH direction. The 5-year leukemia-free survival (LFS) and overall survival (OS) rates after UCBT were 65.8% and 69.6%, respectively. In a multivariate analysis, KIR-ligand mismatch in the GVH direction was associated with a significant reduction in the relapse rate (hazard ratio [HR], 0.19; P = .002), resulting in better LFS (HR, 0.18; P =.010) and OS (HR, 0.26; P = .048) without increasing non-relapse mortality (NRM; HR, 1.90; P = .264). The cumulative incidence of GVH disease (GVHD) did not differ between patients with and without KIR-ligand mismatch (grade II-IV acute GVHD, 39.1% versus 36.8%, P = .648, grade III-IV acute GVHD, 13.0% versus 11.8%, P =.857, and chronic GVHD, 26.1% versus 22.9%, P =.736, respectively). Furthermore, acute and chronic GVHD were not associated with good patient outcomes. Notably, no relapse was observed in patients who received KIR-ligand mismatched UCBT in complete remission. KIR-ligand mismatch in the GVH direction improved LFS and decreased relapse rates without increasing NRM in children and adolescents with T-ALL who received UCBT, which was not mediated by GVHD.
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