Epigenetic Therapy Promotes the Ratio of Th1/Th17 Lineage to Reverse Immune Evasion and Treat Leukemia Relapse Post-allogeneic Stem Cell Transplantation in Non-APL AML Patients.

Yang Xi,Zhang Rong,Li Chenglong,Wang Xiaodong,Zheng Hong,Wang Chunsen,Dai Jingying,Huang Xiaobing

doi:10.3389/fmolb.2020.595395

Abstract

To reverse the early-stage relapse post-hematopoietic stem cell transplantation, we investigated the safety and efficacy of a new epigenetic regimen (chidamide and decitabine plus thymalfasin simultaneously) on acute myeloid leukemia patients (excluding acute promyelocytic leukemia). Twenty-four patients were enrolled in this observational study during April 2015 to May 2018. The most common adverse event was reversible CTCAE grade 2 thrombocytopenia (20/24). Strikingly, all 24 patients had response to this epigenetic regimen accompanied with decreased measurable residual disease. The overall survival rate is 79.2% (19/24), with a relapse-free survival rate of 79.2% (19/24). During this regimen treatment, Th1 cells and CD3+CD4-CD8+T cells increased, and Th17 cells decreased gradually. The status of high Th1 and low Th17 cells was still observed on the 3rd month after discontinuation of this regimen. Interestingly, the significantly elevated ratio of Th1/Th17 seemed to reflect the treatment-related immune effect, which may be a valuable marker to be monitored in the early-relapse stage for evaluating the efficacy and prognosis.

Highlights

Acute myeloid leukemia (AML) is a heterogeneous disorder with high morbidity and mortality
All patients were diagnosed with non-Acute promyelocytic leukemia (APL) AML as per WHO classification and underwent allo-HSCT due to the high-risk features of their disease
According to the 2016 World Health Organization’s criterion for AML patients, the AML patients were divided into a lowrisk group, an intermediate-risk group, and a high-risk group

Summary

Introduction

Acute myeloid leukemia (AML) is a heterogeneous disorder with high morbidity and mortality. According to the prognosis assessment by different characters in morphology, immunophenotype, cytogenetics, and molecular biology, the patients were divided into a low-risk group, an intermediate-risk group, and a high-risk group (Estey, 2018). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective, and sometimes the only, curative post-remission therapy for AML patients. Based on genetic risk classification, the published data have suggested that allo-HSCT may be recommended for high-risk and most intermediate-risk AML but not for low-risk AML in first complete remission (CR1) (Takami, 2018). The role of allo-SCT in low-risk AML in CR1 is being established with the development of a risk-directed, measurable residual disease (MRD)-based strategy (Döhner et al, 2017).

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