Donor-derived natural killer cell infusion after human leukocyte antigen-haploidentical hematopoietic cell transplantation in patients with refractory acute leukemia

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Title
Donor-derived natural killer cell infusion after human leukocyte antigen-haploidentical hematopoietic cell transplantation in patients with refractory acute leukemia
Author(s)
In Pyo Choi; Suk Ran Yoon; Soo-Yeon Park; Hanna Kim; Sol-Ji Jung; Y L Kang; J H Lee; J H Lee; D Y Kim; J L Lee; H S Park; E J Choi; Y S Lee; Y A Kang; M Jeon; M Seol; S Baek; S C Yun; H J Kim; K H Lee
Bibliographic Citation
Biology of Blood and Marrow Transplantation, vol. 22, pp. 2065-2076
Publication Year
2016
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 × 10 8/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%).
Keyword
Acute myelogenous leukemiaDonor natural killer (NK) cell infusionHLA-haploidentical hematopoietic cell transplantation
ISSN
1083-8791
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbmt.2016.08.008
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
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