Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO-positive acute myeloid leukemia

Abstract

Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO-positive acute myeloid cell transplantation. Methods: A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO-positive AML post transplantation but negative flow cytometry results. A retrospective analysis was performed of the survival rate and possible influencing factors of patients with relapse treated with this regimen in our center from January 2018 to January 2022. Results: The overall response rate was 95.8% (23/24), and the median number of treatment courses was 4 (range, 3-12 courses). The total molecular complete response (MCR) was 79.1% (19/24) after all treatments, and the molecular complete response was 37.5% (9/24) after one cycle of treatment but reached 58.3% (14/24) after four cycles; overall, the proportion of MCR increased gradually with the increase in treatment cycles. The projected 5-year overall survival rate was 73.9%. The projected 5-year leukemia-free survival rate was 64.8%, and the projected 1-year cumulative relapse rate was 35.5%. The incidence of grade II-IV graft-versus-host diseases (GVHD) was 29.2% (7/24), and that of grade III-IV GVHD was 20.8% (5/24), which could be effectively controlled by glucocorticoid therapy combined with calcineurin inhibitors The total incidence of chronic GVHD was 29.2% (7/24), and all cases were localized chronic GVHD. The total infection rate was 33.3% (8/24), mainly involving bacterial and fungal infections, and the incidence of life-threatening infections was 4.17% (1/24). The treatment-related mortality rate was 0%; and the total mortality rate was 20.8% (5/24). Nausea and vomiting, thrombocytopenia, and neutropenia were common adverse reactions, all of which were Common Terminology Criteria for Adverse Events grade 2-3 events and reversible after drug withdrawal. In terms of immunity, Th1 cell counts gradually increased, Th17 cell counts gradually decreased, and the Th1/Th17 ratio gradually increased after treatment. The CD8⁺ T lymphocyte count increased gradually, while the CD4⁺ T lymphocyte count did not change significantly. Conclusion: Our chidamide-based 3-drug combination regimen led to a high remission rate and tolerable adverse reactions in patients with AML1-ETO-positive post-transplant relapse, and most patients can achieve long-term survival with this regimen.

Keywords: 3-drug combination; AML1-ETO; chidamide; post-transplantation; relapse.