Format

Send to

Choose Destination
Biol Blood Marrow Transplant. 2016 Nov;22(11):2065-2076. doi: 10.1016/j.bbmt.2016.08.008. Epub 2016 Aug 12.

Donor-Derived Natural Killer Cell Infusion after Human Leukocyte Antigen-Haploidentical Hematopoietic Cell Transplantation in Patients with Refractory Acute Leukemia.

Author information

1
Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. Electronic address: ipchoi@kribb.re.kr.
2
Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
3
Hematology and Oncology Sections, Department of Internal Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
4
Department of Clinical Epidemiology and Biostatistics, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.
5
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.

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%).

KEYWORDS:

Acute myelogenous leukemia; Donor natural killer (NK) cell infusion; HLA-haploidentical hematopoietic cell transplantation

PMID:
27530969
DOI:
10.1016/j.bbmt.2016.08.008
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center