PMID- 24525278
OWN - NLM
STAT- MEDLINE
DCOM- 20141125
LR  - 20140411
IS  - 1523-6536 (Electronic)
IS  - 1083-8791 (Linking)
VI  - 20
IP  - 5
DP  - 2014 May
TI  - Donor-derived natural killer cells infused after human leukocyte 
      antigen-haploidentical hematopoietic cell transplantation: a dose-escalation 
      study.
PG  - 696-704
LID - S1083-8791(14)00076-7 [pii]
LID - 10.1016/j.bbmt.2014.01.031 [doi]
AB  - 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 75 
      years) with hematologic malignancy underwent HLA-haploidentical HCT after 
      reduced-intensity conditioning containing busulfan, fludarabine, and 
      antithymocyte globulin. Cell donors (ages 7 to 62 years) underwent growth 
      factor-mobilized leukapheresis for 3 to 4 days. Cells collected on the first 2 to 
      3 days 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 3 weeks after HCT 
      at an escalating doses of .2 x 10(8) cells/kg of body weight (3 patients), .5 x 
      10(8) cells/kg (3 patients), 1.0 x 10(8) cells/kg (8 patients), and >/= 1.0 x 10(8) 
      cells/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/muL, 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 3 weeks after HLA-haploidentical HCT, donor-derived NK cells were well 
      tolerated at a median total dose of 2.0 x 10(8) cells/kg. In addition, they may 
      decrease post-transplantation progression of acute leukemia.
CI  - Copyright (c) 2014 American Society for Blood and Marrow Transplantation. Published 
      by Elsevier Inc. All rights reserved.
FAU - Choi, Inpyo
AU  - Choi I
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, Korea. Electronic address: ipchoi@kribb.re.kr.
FAU - Yoon, Suk Ran
AU  - Yoon SR
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, Korea.
FAU - Park, Soo-Yeon
AU  - Park SY
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, Korea.
FAU - Kim, Hanna
AU  - Kim H
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, Korea.
FAU - Jung, Sol-Ji
AU  - Jung SJ
AD  - Immunotherapy Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, Korea.
FAU - Jang, Ye Jin
AU  - Jang YJ
AD  - Medical Genomics Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, Korea.
FAU - Kang, Minho
AU  - Kang M
AD  - Medical Genomics Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, Korea.
FAU - Yeom, Young Il
AU  - Yeom YI
AD  - Medical Genomics Research Center, Korea Research Institute of Bioscience and 
      Biotechnology, Daejeon, Korea.
FAU - Lee, Jae-Lyun
AU  - Lee JL
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Kim, Dae-Young
AU  - Kim DY
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Lee, Young-Shin
AU  - Lee YS
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Kang, Young-Ah
AU  - Kang YA
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Jeon, Mijin
AU  - Jeon M
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Seol, Miee
AU  - Seol M
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Lee, Jung-Hee
AU  - Lee JH
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Lee, Je-Hwan
AU  - Lee JH
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Kim, Hwa Jung
AU  - Kim HJ
AD  - Department of Clinical Epidemiology and Biostatistics, University of Ulsan, 
      College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Yun, Sung-Cheol
AU  - Yun SC
AD  - Department of Clinical Epidemiology and Biostatistics, University of Ulsan, 
      College of Medicine, Asan Medical Center, Seoul, Korea.
FAU - Lee, Kyoo-Hyung
AU  - Lee KH
AD  - Hematology and Oncology Sections, Department of Internal Medicine, University of 
      Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea. Electronic 
      address: khlee2@amc.seoul.kr.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140211
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (Myeloablative Agonists)
RN  - FA2DM6879K (Vidarabine)
RN  - G1LN9045DK (Busulfan)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antilymphocyte Serum/therapeutic use
MH  - Busulfan/therapeutic use
MH  - Child
MH  - Disease Progression
MH  - Female
MH  - Graft vs Host Disease/immunology/mortality/pathology
MH  - Hematologic Neoplasms/immunology/mortality/pathology/*therapy
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility Testing
MH  - Humans
MH  - Killer Cells, Natural/immunology/*transplantation
MH  - Lymphocyte Count
MH  - Male
MH  - Middle Aged
MH  - Myeloablative Agonists/*therapeutic use
MH  - Retrospective Studies
MH  - Survival Analysis
MH  - Transplantation Conditioning/*methods
MH  - Transplantation, Homologous
MH  - Vidarabine/analogs & derivatives/therapeutic use
OTO - NOTNLM
OT  - Donor natural killer cell infusion
OT  - Human leukocyte antigen-haploidentical hematopoietic cell transplantation
EDAT- 2014/02/15 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/02/15 06:00
PHST- 2013/11/08 00:00 [received]
PHST- 2014/01/29 00:00 [accepted]
PHST- 2014/02/15 06:00 [entrez]
PHST- 2014/02/15 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S1083-8791(14)00076-7 [pii]
AID - 10.1016/j.bbmt.2014.01.031 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2014 May;20(5):696-704. doi: 
      10.1016/j.bbmt.2014.01.031. Epub 2014 Feb 11.