Epigenetic Therapy Targets Th1/Th17 Polarization to Reversing Immune Evasion and Treating Leukemia Relapse Post Allogeneic Stem Cell Transplantation in Non-APL AML Patients

Abstract

To reverse non-APL AML patients with post-transplantation relapse before hematological relapse(early-stage relapse), we investigated the safety and efficacy of a new epigenetic therapy(DNA methyltransferase inhibitors, Decitabine and histone deacetylase inhibitors, Chidamide, plus Thymalfasin simultaneously). Twenty-four patients were enrolled in this observational study. The most common adverse event was CTCAE grade 2 thrombocytopenia (20/24). No acute GVHD was observed in patients received this treatment regimen. Strikingly all 24 patients responded to this epigenetic therapy with minute residual disease(MRD) decreasing (ORR 100%). At the more than 3-year follow-up, overall survival rate is 87.5%(21/24), with relapse-free survival rate of 75%(18/24). With this epigenetic therapy for 3 months, Th1 cells and CD3+CD4-CD8+T cells increased gradually, and Th17 cells decreased. The status of Th1 and Th17 cells remained at the time of 3 months after discontinuation. Interestingly, the Th1/Th17 ratio was low in patients with relapse disease and then increased gradually during this treatment regimen, correlated with the down trend of MRD. Therefore, our new epigenetic therapy is safe and tolerable for non-APL AML suffering post-transplant early relapse. The polarization for Th1/Th17 and the significant elevated ratio of Th1/Th17 seemed to better reflect the epigenetic therapy-mediated immune effect, which maybe a good biomarker for the early relapse monitoring. DisclosuresNo relevant conflicts of interest to declare.