Clinical Safety of NK Cell in the Prevention of Leukemia Relapse Post-transplantation and in Treatment of the Elderly Leukemia Patients.
10.19746/j.cnki.issn.1009-2137.2022.04.047
- Author:
Jing LIU
1
;
Xiao-Li ZHENG
1
;
Mei XUE
1
;
Ling ZHU
1
;
Li DING
1
;
Dong-Mei HAN
1
;
Hong-Min YAN
1
;
Sheng LI
1
;
Ji-Dong MA
1
;
Xi-Tong TAN
1
;
Jie-Xin ZHOU
1
;
Zi-Kuan GUO
2
;
Heng-Xiang WANG
3
Author Information
1. Department of Hematology, Air Force Medical Center, Beijing 100142, China.
2. Department of Central Lab, Beijing Jingdu Children's Hospital, Beijing 102208, China.
3. Department of Hematology, Air Force Medical Center, Beijing 100142, China .E-mail: wanghengxiang123@aliyun.com.
- Publication Type:Journal Article
- Keywords:
acute myelocytic leukemia;
chemotherapy;
hematopoietic stem cell transplantation;
immunotherapy;
natural killer cell
- MeSH:
Aged;
Graft vs Host Disease/prevention & control*;
Hematopoietic Stem Cell Transplantation;
Humans;
Killer Cells, Natural;
Leukemia, Myeloid, Acute/therapy*;
Middle Aged;
Recurrence
- From:
Journal of Experimental Hematology
2022;30(4):1267-1271
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To observe the safety of donor NK cell infusions in the settings of hematopoietic stem cell transplantation and after consolidation chemotherapy in elderly patients with acute myeloid leukemia (AML).
METHODS:Forty patients with AML were included, in which 21 patients aged over 60 years were at the stage of complete remission (CR) and 19 patients that received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mononucleated cells were isolated from peripheral blood from the donors (for allo-HSCT) or healthy immediate family members (elderly AML). The cells were seeded into the flasks pre-coated with NK cell specific activators, and expanded in media containing recombinant human IL-15 and IL-2 for 14 days. The cells were transfused intravenously after the identification of quality control. Trypan blue exclusion test was used for the determination of cell viability and counting. Flow cytometry analysis was performed to assess the surface antigenic profile. Seventy-eight infusions of the cell products were received by the elderly patients with AML after consolidation chemotherapy, 11 infusions were received by the patients during allo-HSCT and 32 infusions 3 moths after transplantation. The safety of cell therapy, body temperature, blood pressure and other indexes were observe during and 48 hours after cell transfusion. Meanwhile, the occurrence and severity of acute graft-versus-host disease (GVHD) were documented.
RESULTS:Flow cytometry analysis showed that the proportion of NK cells (CD3-CD56+) in the mononucleated cells before culture was (14.10±4.22)% (n=121), and the proportion increased dramatically up to (87.29±8.75)% (n=121) after culture for 14 days, the number of NK cells increased to 753.47±140.13 times (n=121). The doses of the infused NK cells was (7.58±2.50)×107/kg per infusion. Moderate fever occurred in three cases after multiple infusions, and the temperature restored to normal on the same day after treatment. Fever was observed in one patient after every infusion of four times in total. The temperature reached to 38.5-39.0 ℃ and returned to normal within 1-2 hours after adequate antipyretic treatment, and then there was no discomfort. No GVHD was observed in the elderly AML patients, while 6 cases that received allo-HSCT developed moderate acute GVHD, among them grade I in 5 cases and grade II in 1 case. No other severe toxicities were observed.
CONCLUSION:NK cell products with a high-purity could be obtained by ex vivo expansion with this protocol. The transfusion of these expanded cells is generally safe in the elderly patients with AML that have received chemotherapy or patients that received hematopoietic stem cell transplantation.
