Abstract：
The technique of αβ T cell depletion (αβTCD) is a well-established method of hematopoietic stem cell transplantation (HSCT) for children with acute leukemia owing to the low rates of graft-versus-host disease and nonrelapse mortality (NRM). The graft-versus-leukemia effect is generally ascribed to natural killer (NK) cells conserved within the graft. It is not known whether NK-related factors affect the outcome of αβTCD HSCT, however. The aim of this retrospective study was to explore the impact of NK alloreactivity (based on donor-recipient killer immunoglobulin-like receptor [KIR] mismatch), graft NK cell dose, and blood NK cell recovery on day +30 post-HSCT on the incidences of leukemia relapse and NRM. The pediatric acute leukemia cohort comprised 295 patients who underwent their first HSCT from a haploidentical donor in complete remission. During post hoc analysis, the total cohort was divided into subcohorts by diagnosis (acute lymphoblastic leukemia [ALL]/acute myeloid leukemia [AML]), NK alloreactivity prediction (KIR match/KIR mismatch), graft NK cell dose (less than versus greater than the median value), and blood NK cell recovery on day +30 post-HSCT (less than versus greater than the median value). We also investigated the influence of serotherapy (antithymocyte globulin [ATG] group) versus abatacept + tocilizumab combination [aba+toci] group) on relapse risk in the context of KIR mismatch. The risks of relapse and NRM were calculated by the cumulative risk method, and groups were compared using the Gray test. Multivariate analysis revealed no apparent impact of predicted NK alloreactivity or any other studied NK cell-related factors for the entire cohort. For patients with AML, a significantly higher relapse risk associated with high NK cell graft content on the background of no predicted KIR mismatch (P = .002) was shown. Multivariate analysis confirmed this finding (P = .018); on the other hand, for the KIR-mismatched patients, there was a trend toward a lower risk of relapse associated with high NK cell dose. The use of ATG was associated with a trend toward reduced relapse risk (P = .074) in the AML patients. There was no significant impact of NK-related factors in the ALL patients. Overall, the evaluated NK-related factors did not show a clear and straightforward correlation with the key outcomes of HSCT in our cohort of children with acute leukemia. In practice, the data support prioritization of KIR-mismatched donors for patients with AML. Importantly, a potential interaction of KIR ligand mismatch and NK cell content in the graft was identified. Indirect evidence suggests that additional cellular constituents of the graft could influence the function of NK cells after HSCT and affect their role as graft-versus-leukemia effectors.
摘要：
背景：αβT细胞耗竭（αβTCD）是一种针对急性白血病儿童的公认的HSCT方法，原因是移植物抗宿主疾病和非复发死亡率低。移植物抗白血病效应通常归因于NK细胞，保存在移植物内。然而,目前尚不清楚NK相关因素是否会影响αβTCDHSCT的预后。
目的：这项回顾性研究的目的是探索NK-同种异体反应性（基于供体-受体KIR错配）的影响，移植物NK细胞剂量，HSCT后30天的血液NK细胞恢复对白血病复发和非复发死亡率（NRM）的影响。
方法：儿童急性白血病队列包括295例首次从单倍体供体移植并完全缓解的患者。在事后分析期间，总队列按诊断分为亚组（ALL/AML），NK同种反应性预测（KIR匹配/KIR不匹配），移植物NK细胞剂量（较少大于中值)，和HSCT后第30天的血液NK细胞恢复（较少大于中值)。我们还研究了血清疗法（ATG组）与abatacept+tocilizumab组合（aba+toci组）在KIR不匹配背景下对复发风险的影响。通过累积风险法计算复发和NRM风险，并通过Gray检验比较各组。提供多变量分析。
结果：预测的NK同种反应性没有明显影响，或其他研究的NK相关因素为总队列。对于AML患者，在没有预测的KIR错配的背景下,与高NK移植物含量相关的复发风险显著较高(p=0.002).多变量分析证实了这一发现(p=0.018)；另一方面，对于KIR不匹配队列，高NK细胞剂量有降低复发风险的趋势.使用ATG与AML队列的复发风险降低趋势相关(p=0.074)。NK相关因素对ALL患者无显著影响。
结论：总体而言，在整个急性白血病儿童队列中,评估的NK相关因子与HSCT的关键结局没有明确和直接的相关性.在实践中,数据支持对AML患者进行KIR不匹配供体的优先排序.重要的是,确定了移植物中KIR配体错配和NK细胞含量的潜在相互作用。间接证据表明，移植物的其他细胞成分可能会影响HSCT后NK细胞的功能，并影响其作为GVL效应物的作用。
目的：这项回顾性研究的目的是探索NK-同种异体反应性（基于供体-受体KIR错配）的影响，移植物NK细胞剂量，HSCT后30天的血液NK细胞恢复对白血病复发和非复发死亡率（NRM）的影响。
方法：儿童急性白血病队列包括295例首次从单倍体供体移植并完全缓解的患者。在事后分析期间，总队列按诊断分为亚组（ALL/AML），NK同种反应性预测（KIR匹配/KIR不匹配），移植物NK细胞剂量（较少大于中值)，和HSCT后第30天的血液NK细胞恢复（较少大于中值)。我们还研究了血清疗法（ATG组）与abatacept+tocilizumab组合（aba+toci组）在KIR不匹配背景下对复发风险的影响。通过累积风险法计算复发和NRM风险，并通过Gray检验比较各组。提供多变量分析。
结果：预测的NK同种反应性没有明显影响，或其他研究的NK相关因素为总队列。对于AML患者，在没有预测的KIR错配的背景下,与高NK移植物含量相关的复发风险显著较高(p=0.002).多变量分析证实了这一发现(p=0.018)；另一方面，对于KIR不匹配队列，高NK细胞剂量有降低复发风险的趋势.使用ATG与AML队列的复发风险降低趋势相关(p=0.074)。NK相关因素对ALL患者无显著影响。
结论：总体而言，在整个急性白血病儿童队列中,评估的NK相关因子与HSCT的关键结局没有明确和直接的相关性.在实践中,数据支持对AML患者进行KIR不匹配供体的优先排序.重要的是,确定了移植物中KIR配体错配和NK细胞含量的潜在相互作用。间接证据表明，移植物的其他细胞成分可能会影响HSCT后NK细胞的功能，并影响其作为GVL效应物的作用。
