Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients
Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients
复制标题
DOI：
10.1182/blood-2011-01-329508
复制
发表时间：
2011-09-22
期刊：
影响因子：
20.3
通讯作者：
Lemoli, Roberto M.
中科院分区：
文献类型：
--
作者：
Curti, Antonio;Ruggeri, Loredana;Lemoli, Roberto M.
13例急性髓系白血病患者，5例活动期，2例分子复发，6例形态完全缓解(CR；中位年龄，62岁；年龄53~73岁)，在氟达拉滨/环磷酰胺免疫抑制化疗后，从半相合的杀伤免疫球蛋白受体配体不匹配的供者体内获得高纯度的CD56(+)CD3(-)自然杀伤(NK)细胞。输注NK细胞的中位数为2.74×10(6)/kg。T细胞为10(5)/kg。未观察到包括移植物抗宿主病在内的NK细胞相关毒性。5例活动性疾病患者中有1例获得一过性CR，而5例患者中有4例没有临床益处。两例分子复发者分别获得9个月和4个月的完全缓解。6名CR患者中有3名分别在34、32和18个月后无病。输注后，所有可评价患者外周血中均可检测到供者NK细胞(高峰在第10天)。在某些情况下，它们也在骨髓中被检测到。通过检测杀死受者靶标的供者来源的NK克隆，体内显示了供者对受者的同种异体反应性NK细胞。过继转移的NK细胞对包括白血病在内的受体细胞具有同种异体反应。结论：对老年高危急性髓系白血病患者输注纯化的NK细胞是可行的。这项试验在www.ClinicalTrial.gov上注册为NCT00799799。(血。2011；118(12)：3273-3279)
Thirteen patients with acute myeloid leukemia, 5 with active disease, 2 in molecular relapse, and 6 in morphologic complete remission (CR; median age, 62 years; range, 53-73 years) received highly purified CD56(+)CD3(-) natural killer (NK) cells from haploidentical killer immunoglobulin-like receptor-ligand mismatched donors after fludarabine/cyclophosphamide immunosuppressive chemotherapy, followed by IL-2. The median number of infused NK cells was 2.74 x 10(6)/Kg. T cells were < 10(5)/Kg. No NK cell-related toxicity, including GVHD, was observed. One of the 5 patients with active disease achieved transient CR, whereas 4 of 5 patients had no clinical benefit. Both patients in molecular relapse achieved CR that lasted for 9 and 4 months, respectively. Three of 6 patients in CR are disease free after 34, 32, and 18 months. After infusion, donor NK cells were found in the peripheral blood of all evaluable patients (peak value on day 10). They were also detected in BM in some cases. Donor-versus-recipient alloreactive NK cells were shown in vivo by the detection of donor-derived NK clones that killed recipient's targets. Adoptively transferred NK cells were alloreactive against recipient's cells, including leukemia. In conclusion, infusion of purified NK cells is feasible in elderly patients with high-risk acute myeloid leukemia. This trial was registered at www.clinicaltrial.gov as NCT00799799. (Blood. 2011;118(12):3273-3279)