Expandation of CD56-Bright NK Cell in Patients with Steroid-Refractory Graft-Versus-Host Disease Treated with Basiliximab and Etanercept

Objectives: Steroid-resistant aGVHD(SR-aGVHD) is a complication with high incidence of mortality following allogeneic stem cell transplantation. Our previous study has showed combined treatment by basiliximab and etanercept achieved high response in SR-aGVHD. The aim of this study is to investigate the changes of lymphocyte subsets in SR-aGVHD following treatment with basiliximab and etanercept.

Methods: We treated 11 SR-aGVHD patients with basiliximab 20mg on days 1, 4, 8, 15, and etanercept 25 mg twice a week for 4 weeks, followed by once weekly for 4 more weeks. Their peripheral blood lymphocyte subsets were assessed by flow cytometry before and after treatment.

Results: The overall response to treatment was 100% (11/11) with 72.7% (8/11) achieving a complete response. As expected, we found a significant depletion of both CD4+ and CD8+ T-cell subset at 4w following treatment. Conversely, the proportion of CD3-CD56+NK expanded significantly, accounting for 26.82±7.69% of PB lymphocytes at 6w following treatment, compared with 10.90±3.94% before treating. The increasement in NK proportion lasting from several weeks to several months. Moreover, the percentage of CD56bright and IFN-gamma-producing NK cell subsets also increased after combined treatments.

Conclusion: Expansion of CD56(bright) and IFN-gamma production NK cell subsets and contraction of CD4(+) and CD8(+) T cell numbers may contribute to the well control of SRaGVHD by basiliximab and etanercept. This finding provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during aGVHD.