Abstract：
Clinical effect of donor-derived natural killer cell infusion (DNKI) after HLA-haploidentical hematopoietic cell transplantation (HCT) was evaluated in high-risk myeloid malignancy in phase 2, randomized trial. Seventy-six evaluable patients (aged 21-70 years) were randomized to receive DNKI (N = 40) or not (N = 36) after haploidentical HCT. For the HCT conditioning, busulfan, fludarabine, and anti-thymocyte globulin were administered. DNKI was given twice 13 and 20 days after HCT. Four patients in the DNKI group failed to receive DNKI. In the remaining 36 patients, median DNKI doses were 1.0 × 108/kg and 1.4 × 108/kg on days 13 and 20, respectively. Intention-to-treat analysis showed a lower disease progression for the DNKI group (30-month cumulative incidence, 35% vs 61%, P = 0.040; subdistribution hazard ratio, 0.50). Furthermore, at 3 months after HCT, the DNKI patients showed a 1.8- and 2.6-fold higher median absolute blood count of NK and T cells, respectively. scRNA-sequencing analysis in seven study patients showed that there was a marked increase in memory-like NK cells in DNKI patients which, in turn, expanded the CD8+ effector-memory T cells. In high-risk myeloid malignancy, DNKI after haploidentical HCT reduced disease progression. This enhanced graft-vs-leukemia effect may be related to the DNKI-induced, post-HCT expansion of NK and T cells. Clinical trial number: NCT02477787.
摘要：
在2期随机试验中，在高危骨髓性恶性肿瘤中评估了HLA单倍体相合造血细胞移植（HCT）后供体来源的自然杀伤细胞输注（DNKI）的临床效果。76名可评估患者（21-70岁）在单倍体HCT后随机接受DNKI（N=40）或不接受DNKI（N=36）。对于HCT调节，白消安,氟达拉滨,给予抗胸腺细胞球蛋白。在HCT后13天和20天给予DNKI两次。DNKI组中有4名患者未能接受DNKI。在剩下的36名患者中，第13天和第20天的中位DNKI剂量分别为1.0×108/kg和1.4×108/kg.意向治疗分析显示DNKI组的疾病进展较低（30个月累积发生率，35%vs61%，P=0.040；子分布危险比，0.50).此外，在HCT后3个月，DNKI患者显示NK和T细胞的中位绝对血细胞计数高1.8倍和2.6倍，分别。7名研究患者的scRNA测序分析表明，DNKI患者的记忆样NK细胞明显增加，反过来,扩增CD8+效应记忆T细胞。在高危骨髓恶性肿瘤中，单倍体HCT后的DNKI减少了疾病进展。这种增强的移植物抗白血病效应可能与DNKI诱导的，NK和T细胞的HCT扩增后。临床试验编号：NCT02477787。
