ATO/ATRA/anthracycline-chemotherapy sequential consolidation achieves long-term efficacy in primary acute promyelocytic leukemia.

Zi-Jie Long,Dong-Ning Wang,Dong-Jun Lin,Quentin Liu,Zhi-Gang Fang,Ren-Wei Huang,Jia-Jun Liu,Jin-Song Yan,Yuan Hu,Ruo-Zhi Xiao,Xu-Dong Li,Yi He,Francesco Bertolini

doi:10.1371/journal.pone.0104610

Abstract

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse-free survival (RFS) were 94.4%±3.9% and 94.6±3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL.

Highlights

Acute promyelocytic leukemia (APL), characterized by the t (15, 17) chromosomal translocation and leukemogenic PML-RARa fusion protein, is accumulated of abnormal promyelocytes in the bone marrow and causes severe bleeding tendency [1]
The induction of all-trans retinoic acid (ATRA) in the treatment and optimization of the anthracycline-based regimens resulted in terminal differentiation of APL cells with a 90–95% complete remission (CR) and the 5year disease-free survival (DFS) up to 74% [1,4,5], approximately 5–30% of patients developed disease recurrence [6]
ATRA in combination with anthracycline-based chemotherapy is considered as the standard for the induction and consolidation therapy of newly diagnosed APL

Summary

Introduction

Acute promyelocytic leukemia (APL), characterized by the t (15, 17) chromosomal translocation and leukemogenic PML-RARa fusion protein, is accumulated of abnormal promyelocytes in the bone marrow and causes severe bleeding tendency [1]. The treatment of APL with chemotherapy achieved complete remission (CR) in two-thirds of newly diagnosed patients, the 5-year disease-free survival (DFS) was still very poor [1,2,3]. The induction of all-trans retinoic acid (ATRA) in the treatment and optimization of the anthracycline-based regimens resulted in terminal differentiation of APL cells with a 90–95% CR and the 5year DFS up to 74% [1,4,5], approximately 5–30% of patients developed disease recurrence [6]. Strong synergistic anti-leukemic effects of ATO in combination with ATRA were found in both APL cell lines and APL animal models, with induction catabolism of the PML-RARa fusion protein [14,15,16,17]. A standard ATO/ATRA consolidation regimen for newly diagnosed APL remains to be further validated

Methods

Results

Conclusion