肿瘤细胞治疗研究
英文原题：Higher Dose of CD34(+) cells Promotes Early Reconstitution of Natural Killer Cells and Is Associated with Better Outcomes After Unmanipulated Hematopoietic Stem Cell Transplantation for Myeloid Malignancies.
我们回顾性分析了 180 例接受未经处理的同种异体移植物的急性髓系白血病或骨髓增生异常综合征患者。
异基因造血干细胞移植（allo-HSCT）后，NK 细胞是最早恢复的淋巴细胞群体，可介导强效移植物抗白血病作用，尤其是在 T 细胞清除背景下。然而，在未操作移植后的 NK 细胞作用尚不明确，影响早期 NK 细胞重建的因素也仍未阐明。我们回顾性分析 180 例接受未操作异基因移植物的急性髓系白血病或骨髓增生异常综合征患者，重点研究早期 NK 细胞重建及其与疾病复发、总生存期和巨细胞病毒（CMV）再激活的关联；还分析影响 NK 恢复的因素，如移植物中 CD34⁺ 细胞剂量和移植后 T 细胞恢复。惩罚样条和受试者工作特征曲线显示，allo-HSCT 后第 30 天血液 NK 细胞计数（NK30）与全因死亡率密切相关，其截断值接近可将患者分为两组的中位数。进一步分析显示，NK 快速恢复（NK30 或 NK60 较高）与较低疾病复发率和更好生存相关。NK 恢复良好（NK30 和 NK60 较高）也与较低 CMV 再激活发生率相关。我们发现 NK30 与移植物中 CD34⁺ 细胞数量相关（r=0.739，P<0.001），但与移植物所含成熟 NK 细胞数量无关。在队列的一个小亚组（N=12）中，持续完全缓解患者（N=6）移植后第 30 天骨髓中的 CD34⁺CD7⁺ 祖细胞和 CD56 明亮型 NK 细胞频率，高于 1 年内疾病复发患者（N=6）。此外，移植后 T 细胞恢复和预处理方案中使用抗胸腺细胞球蛋白（ATG）均未显示对 NK 恢复的抑制作用。NK 细胞快速恢复与未操作移植治疗髓系恶性肿瘤后的预后改善相关。调节 NK 细胞恢复是改善移植结局的可行方法，例如优化移植物中的 CD34⁺ 细胞。
Natural killer (NK) cells are the first lymphocyte population to recover after allogenic hematopoietic stem cell transplantation (allo-HSCT) and mediate potent graft versus leukemia effect, particularly in the settings of T-cell depletion. However, the significance of NK cells after unmanipulated transplantation is less clear, and factors affecting early NK reconstitution remain elusive. We retrospectively analyze 180 patients with acute myeloid leukemia or myelodysplastic syndrome who received unmanipulated allografts. We focus on the early NK reconstitution and its association with disease relapse, overall survival, and cytomegalovirus (CMV) reactivation. We also analyze factors that affect NK recovery, such as dose of CD34 + cells in the graft and T-cell recovery after transplantation. Penalized splines and receiver operator characteristic curves demonstrate a strong association between blood NK counts at 30 days after allo-HSCT (NK30) and all-cause mortality, with the cutoff value being close to the median value that divides patients dichotomously. Subsequent analysis shows that rapid NK recovery (higher NK30 or higher NK60) is associated with reduced disease relapse and better survival. Robust NK recovery (NK30 and NK60) also correlates with lower incidence of CMV reactivation. We find that NK30 is associated with the numbers of CD34 + cells (r = 0.739, P < .001) but not mature NK cells contained in the graft. In a small subset (N = 12) of the cohort, patients in continuous complete remission (N = 6) demonstrate higher frequencies of CD34 + CD7 + progenitor cells and CD56 bright NK cells in the day 30 bone marrow as compared to patients with disease relapse within 1 year (N = 6). Furthermore, neither T-cell recovery after transplantation nor application of anti-thymocyte globulins (ATG) in the conditioning regimen demonstrate suppressive effect on NK recovery. Rapid NK cell recovery is associated with improved prognosis of unmanipulated transplantation for myeloid malignancies. Manipulation of NK cell recovery represents a feasible approach to improve transplant outcomes for example by optimizing CD34 + cells in the graft.
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