Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients

Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients
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DOI:
10.1158/1078-0432.ccr-16-2981
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发表时间:
2017-08-01
影响因子:
11.5
通讯作者:
Schaap, Nicolaas M.
Schaap, Nicolaas M.
中科院分区:
医学1区
文献类型:
--
作者:
Dolstra, Harry;Roeven, Mieke W. H.;Schaap, Nicolaas M.

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目的:老年急性髓细胞白血病(AML)患者预后差,因此需要新的治疗方法。同种异体自然杀伤(NK)细胞已被过继转移,具有良好的临床效果。在这里,我们报告了第一个非人研究,利用从部分HLA匹配的脐带血单位的CD 34(+)造血干细胞和祖细胞(HSPC)离体产生的独特的可扩展NK细胞产物。10例形态学完全缓解的老年AML患者接受了递增的HSPC-NK细胞剂量结果:HSPC-NK细胞产品含有中位数为75%的高活化NK细胞,
Purpose: Older acute myeloid leukemia (AML) patients have a poor prognosis; therefore, novel therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. Here, we report the first-inhuman study exploiting a unique scalable NK-cell product generated ex vivo from CD34(+) hematopoietic stem and progenitor cells (HSPC) from partially HLA-matched umbilical cord blood units.Experimental Design: Ten older AML patients in morphologic complete remission received an escalating HSPC-NK cell dose (between 3 and 30 x 10(6)/kg body weight) after lymphodepleting chemotherapy without cytokine boosting.Results: HSPC-NK cell products contained a median of 75% highly activated NK cells, with