Delay expression of NKp30 on NK cells correlates with long-term mycophenolate mofetil treatment and higher EBV viremia post allogenic hematological stem cells transplantation.


Peking University People's Hospital and Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Beijing Engineering Lab for Cell Therapy, Beijing, China. Electronic address: [Email]


Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in graft-versus-host disease prophylaxis because of its inhibitory function on T cells and B cells. However, the effect of MMF on natural killer cell reconstitution after allogenic hematological transplantation is largely unknown. The present study examined the effects of different MMF administration durations after haploidentical allo-HSCT on NK cell reconstitution. Ninety patients were enrolled in this study and defined into two groups in term of MMF duration. We found that MMF patients in the long-term MMF group were associated with a poor reconstitution of NK cells and a significantly lower cytotoxicity from day 30 to day 180 post-transplantation. Especially, the long-term MMF group inhibits reconstitution of NKp30 NK subsets, which correlated with higher risk of EBV viremia. Multivariate analysis showed that a better reconstitution of NKp30 cells was associated with lower EBV viremia (HR0.957, p = .04). In vitro experiments demonstrated that the active metabolite of MMF, mycophenolic acid (MPA), inhibited the proliferation and cytotoxicity of NK cells from healthy donors or patients at day 30 post-transplantation. In summary, our findings demonstrated that long-term MMF administration delayed the quality and quantity of NK cells, especially NKp30 subpopulations, which was associated with decreased EBV viremia post allogeneic HSCT.


Allo-HSCT,MMF,NK cells,NKp30,Reconstitution,