title: Donor-Derived Natural Killer Cell Infusion after Human Leukocyte Antigen-Haploidentical Hematopoietic Cell Transplantation in Patients with Refractory Acute Leukemia.
abstract: The optimum method of donor natural killer cell infusion (DNKI) after allogeneic hematopoietic cell transplantation (HCT) remains unclear. Fifty-one patients (age range, 19 years to 67 years) with refractory acute leukemia underwent HLA-haploidentical HCT and underwent DNKI on days 6, 9, 13, and 20 of HCT. Median DNKI doses were .5, .5, 1.0, and 2.0 × 108/kg cells, respectively. During DNKI, 33 of the 45 evaluated patients (73%) developed fever (>38.3°C) along with weight gain (median, 13%; range, 2% to 31%) and/or hyperbilirubinemia (median, 6.2 mg/dL; range, 1.0 mg/dL to 35.1 mg/dL); the toxicity was reversible in 90% of patients. After transplantation, we observed cumulative incidences of neutrophil engraftment (≥500/µL), grade 2 to 4 acute graft-versus-host disease (GVHD), chronic GVHD, and nonrelapse mortality of 84%, 28%, 30%, and 16%, respectively. The leukemia complete remission rate was 57% at 1 month after HCT and 3-year cumulative incidence of leukemia progression was 75%. When analyzed together with our historical cohort of 40 patients with refractory acute leukemia who underwent haploidentical HCT and DNKI on days 14 and 21 only, higher expression of NKp30 (>90%) on donor NK cells was an independent predictor of higher complete remission (hazard ratio, 5.59) and less leukemia progression (hazard ratio, .57). Additional DNKI on days 6 and 9 was not associated with less leukemia progression (75% versus 55%).
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. Electronic address: ipchoi@kribb.re.kr.
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Hanna
authors.initials: H
authors.lastname: Kim
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Sol-Ji
authors.initials: SJ
authors.lastname: Jung
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: You-Lee
authors.initials: YL
authors.lastname: Kang
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Han-Seung
authors.initials: HS
authors.lastname: Park
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Young-Shin
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Young-A
authors.initials: YA
authors.lastname: Kang
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Mijin
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Miee
authors.initials: M
authors.lastname: Seol
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Baek
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Sung-Cheol
authors.initials: SC
authors.lastname: Yun
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. Electronic address: khlee2@amc.seoul.kr.
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007694:Killer Cells, Natural / Q000637:transplantation*; D007938:Leukemia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy / Q000379:methods; D014019:Tissue Donors; D000075442:Transplantation, Haploidentical / Q000379:methods*; D055815:Young Adult
chemical_list: D006680:HLA Antigens
keywords: Acute myelogenous leukemia; Donor natural killer (NK) cell infusion; HLA-haploidentical hematopoietic cell transplantation