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异体自然杀伤细胞输注治疗单倍体造血干细胞移植后复发的急性髓系白血病 1 例

Infusion of allogeneic natural killer cells in a patient with acute myeloid leukemia in relapse after haploidentical hematopoietic stem cell transplantation.

机构信息

Service d'Hématologie Clinique, Service de Thérapie Cellulaire, and the Laboratoire d'Immunologie Cellulaire et Tissulaire, Hôpital Pitié-Salpêtrière, Paris, France.

出版信息

Transfusion. 2011 Aug;51(8):1769-78. doi: 10.1111/j.1537-2995.2010.03058.x. Epub 2011 Feb 18.

Abstract

BACKGROUND

Allogeneic donor natural killer (NK)-cell infusion (NK-DLI) is a promising immunotherapy for patients with hematologic disorders.

CASE REPORT

This report describes the case of a patient who received a single haploidentical NK-DLI for a relapse of acute myeloid leukemia (AML) after haploidentical hematopoietic stem cell transplantation. He underwent a cytoreductive, immunosuppressive regimen before NK-DLI and received high-dose interleukin-2 in vivo for 8 weeks afterward.

RESULTS

No major adverse effect was observed. Prospective phenotypic and functional studies of the NK cells showed major expansion of infused NK cells and, more importantly, of the alloreactive KIR2DL1+KIR2DL2/DL3-NKG2A- subset, which reached 117×10(6) cells/L on Day +14 after NK-DLI, the greatest expansion of infused alloreactive NK cells reported so far. Infused NK cells conserved their lytic capacities against K562 target cells and primary AML-mismatched blasts.

CONCLUSION

We review the literature to clarify these data and to detail the indications for allogeneic NK-DLI, the criteria for determining the most suitable donor, the types of conditioning regimens, and the procedures for selecting and activating NK cells.

摘要

背景

异体供者自然杀伤 (NK)-细胞输注 (NK-DLI) 是一种有前途的免疫疗法,适用于血液系统疾病患者。

病例报告

本报告描述了一名患者的病例,该患者在 HLA 半相合造血干细胞移植后复发急性髓系白血病 (AML) ,接受了单次 HLA 半相合 NK-DLI。在 NK-DLI 之前,他接受了细胞减少、免疫抑制方案,之后接受了 8 周的高剂量白细胞介素-2 体内治疗。

结果

未观察到主要不良反应。对 NK 细胞的前瞻性表型和功能研究表明,输注的 NK 细胞,更重要的是,同种异体反应性 KIR2DL1+KIR2DL2/DL3-NKG2A-亚群发生了大量扩增,在 NK-DLI 后第 14 天达到 117×10(6)个细胞/L,这是迄今为止报道的输注同种异体反应性 NK 细胞的最大扩增。输注的 NK 细胞保留了对 K562 靶细胞和原发性 AML 错配的裂解能力。

结论

我们回顾了文献,以阐明这些数据,并详细介绍异体 NK-DLI 的适应证、确定最合适供者的标准、预处理方案的类型,以及 NK 细胞的选择和激活程序。

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