Randomised controlled phase-2 trial to determinate the efficacy of adoptive immunotherapy with haploidentical natural killer cells in high-risk acute myeloid leukemia (HINKL)

大多数被诊断为急性髓细胞白血病（AML）的患者年龄超过60岁。这些患者中有三分之一有染色体变化，这使得疾病非常具有侵袭性，即使用强化化疗治疗，也只会导致4-6个月的灾难性预后。由于供体免疫细胞对患者白血病细胞的免疫反应，来自匹配供体的干细胞移植（SCT）可以显着改善预后。然而，并不是所有的患者都有匹配的供体，许多患者的身体状况不足以承受令人筋疲力尽的移植手术。对于这些患者来说，从他们的兄弟姐妹或后代中输注特殊的免疫细胞，即所谓的NK细胞，是一种有希望的治疗选择。NK细胞还能够诱导针对白血病细胞的免疫反应，并且输血不像SCT那样消耗体力。NK细胞的抗白血病作用此前已在多项试验中得到证实，然而，这些数据大部分来源于儿童研究，其结果尚未与标准化疗治疗进行比较。在这里提出的HINKL试验中，没有SCT选择的高风险AML老年患者将接受标准化疗以减少白血病负担，一旦成功，他们将接受标准化疗以巩固治疗或NK细胞移植。两组的生存率将在两年后进行比较。该试验的目的是证明NK细胞治疗比标准化疗具有更好的预后。

Most patients diagnosed with acute myeloid leukemia (AML) are older than 60 years. One third of these patients have chromosomal changes which make the disease very aggressive and lead to a disastrous prognosis of only 4-6 months even when treated with intensive chemotherapy. Stem cell transplantation (SCT) from a matched donor can improve the prognosis considerably due to immune reactions of donor immune cells against the patient’s leukemia cells. However, not all patients have a matched donor, and many are not fit enough to stand the exhausting transplantation procedure. For these patients, the transfusion of special immune cells, so called NK cells, from their siblings or offspring is a promising treatment option. The NK cells are also able to induce immune reactions against leukemia cells, and the transfusion is not as exhausting as SCT. The anti-leukemia effect of NK cells has been shown in a number of trials before, however, most of these data originate from studies in children, and the results have not been compared with the standard chemotherapy treatment. In the HINKL trial proposed here, elderly patients with a high-risk AML who have no option for a SCT will receive a standard chemotherapy in order to reduce the leukemia burden and once this was successful, they will receive either the standard chemotherapy for treatment consolidation or the NK cell transplantation. The survival of both groups will be compared after two years. The goal of the trial is to show that treatment with NK cells conveys a better prognosis than standard chemotherapy.