Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study

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Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study
In Pyo Choi; Suk Ran Yoon; Soo Yeon Park; Hanna Kim; Sol-Ji Jung; Ye Jin Jang; Min Ho KangYoung Il Yeom; J L Lee; D Y Kim; Y S Lee; Y A Kang; M Jeon; M Seol; J H Lee; J H Lee; H J Kim; S C Yun; K H Lee
Bibliographic Citation
Biology of Blood and Marrow Transplantation, vol. 20, no. 5, pp. 696-704
Publication Year
The doses of donor-derived natural killer (NK) cells that can be given safely after human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) remain to be defined. Forty-one patients (ages 17 to 75years) with hematologic malignancy underwent HLA-haploidentical HCT after reduced-intensity conditioning containing busulfan, fludarabine, and antithymocyte globulin. Cell donors (ages 7 to 62years) underwent growth factor-mobilized leukapheresis for 3 to 4days. Cells collected on the first 2 to 3days were used for HCT, whereas those collected on the last day were CD3-depleted and cultured into NK cells using human interleukins-15 and -21. These NK cells were then infused into patients twice at 2 and 3weeks after HCT at an escalating doses of.2×108cells/kg of body weight (3 patients), 5×108cells/kg (3 patients), 1.0×108cells/kg (8 patients), and ≥ 1.0×108cells/kg or available cells (27 patients). At all dose levels, no acute toxicity was observed after NK cell infusion. After HLA-haploidentical HCT and subsequent donor NK cell infusion, when referenced to 31 historical patients who had undergone HLA-haploidentical HCT after the same conditioning regimen but without high-dose NK cell infusion, there was no significant difference in the cumulative incidences of major HCT outcomes, including engraftment (absolute neutrophil count≥500/μL, 85% versus 87%), grade 2 to 4 acute graft-versus-host disease (GVHD, 17% versus 16%), moderate to severe chronic GVHD (15% versus 10%), and transplantation-related mortality (27% versus 19%). There was, however, a significant reduction in leukemia progression (74% to 46%), with post-transplantation NK cell infusion being an independent predictor for less leukemia progression (hazard ratio, 527). Our findings showed that, when given 2 to 3weeks after HLA-haploidentical HCT, donor-derived NK cells were well tolerated at a median total dose of 2.0×108cells/kg. In addition, they may decrease post-transplantation progression of acute leukemia.
Donor natural killer cell infusionHuman leukocyte antigen-haploidentical hematopoietic cell transplantation
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Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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