Application of NK Cells in ASCT Peritransplantation of Multiple Myeloma
Authors: Bao Yangyi , Guo Kunyuan , Liu Yuanyuan , Jiang Beilei , Zeng Zhijian , Wu Jianwei , Che Su , Zhang Mingjie , Yang Mingzhen 
Published: October 2019

Abstract
BACKGROUND
Significant progress has been made in the therapy of multiple myeloma (MM) with the autologous hematopoietic stem cell transplantation(ASCT) in recent years. But the relapse after transplantation is still the main problem because the grafts are often contaminated by tumor cells and have no effect of anti myeloma. The residual myeloma cells are reduced by increasing doses of cytotoxic drug in the pretreatment. But the related mortality of ASCT is increased because of side effects and complications. Therefore, the pretreatment of MM hasn't changed very much in recent 50 years. So it is urgent to find a new pretreatment to improve curative effect which has small side effects. Natural killer (NK) cells are the principal effector cells in the innate immune system. They have extensive biological functions including anti-tumor and antiviral effects, etc. There is no report about applying NK cells as a pretreatment for ASCT to treat MM so far. In this study, NK cells were added to the pretreatment of ASCT to treat MM We hope NK cells can increase the curative effect and reduce relapse rate, but not increase the side effects. Meanwhile, they can clear myeloma cells without killing by chemotherapy drugs and to decrease infection in transplantation.
OBJECTIVE
To observe the safety and effectiveness of the technology by applying NK cells in peritransplantation of MM ASCT.
METHODS
The ages of 8 MM patients including 7 males and 1 female were 42-62 years, the median age was 51 years, 2 patents of CR and 6 patents of PR before transplantation. The method of NK cell culture: membrane embedded active factor culture system. The pretreatment mainly based on standard Melphalan or busulfan. NK cells were infused to 2 cases back 6-7days after infusing stem cell, and to 6 cases back 24-48 hours before infusing stem cells and 48 hours after chemotherapy as a part of pretreatment in transplantation. Stem cell infusion volume: the number of CD34+ cell 2.2-4.0×106/kg, the number of mononuclear cells 4.3-5.8×106/kg. NK cell infusion volume: 16-160×106/kg. we observed the adverse reactions, recovery time of blood cells and the curative effects.
RESULTS
There were no instances of fever, rash, diarrhea,shock, and other adverse reactions in this study. Recovery time of hematopoietic cells was: 7-14d of granulocyte and 9d of the median time, 9-34d of platelet and 11d of the median time. Fever(38-39 degrees) occurred in 6 patients during the inhibitory period of bone marrow after ASCT. Infection is the major cause of fever in patients receiving ASCT. We evaluated therapeutic effect 3 months after transplantation was 3 cases of CR and 5 cases of PR in 8 patients. The effect 6 months after transplantation was 3 cases of CR and 3 cases of PR in 6 patients. 8 patients were given thalidomide for maintenance therapy. The follow-up time was 3-29 months, median follow-up time was 11 months. Up to the present, there was no death case.
CONCLUSIONS
It was safe and effective to infuse autologous NK cells back in peritransplantation of MM ASCT. Storm effect of inflammatory factors didn't occur during this study. We will expand the number of cases for further clinical research to observe the long-term therapeutic effects and adverse reactions.

Disclosures
No relevant conflicts of interest to declare.