Improved long-term survival in all Sanz risk patients of newly diagnosed acute promyelocytic leukemia treated with a combination of retinoic acid and arsenic trioxide-based front-line therapy

Yinjun Lou; Ying Lu; Zhijuan Zhu; Yafang Ma; Shanshan Suo; Yungui Wang; Dong Chen; Hongyan Tong; Wenbin Qian; Haitao Meng; Wenyuan Mai; Wenjun Yu; Weilai Xu; Lei Wang; Liping Mao; Renzhi Pei; Jie Jin

doi:10.1002/hon.2519

Improved long-term survival in all Sanz risk patients of newly diagnosed acute promyelocytic leukemia treated with a combination of retinoic acid and arsenic trioxide-based front-line therapy

Hematol Oncol. 2018 Jun 3. doi: 10.1002/hon.2519. Online ahead of print.

Authors

Yinjun Lou¹, Ying Lu², Zhijuan Zhu^{1

3}, Yafang Ma¹, Shanshan Suo¹, Yungui Wang¹, Dong Chen², Hongyan Tong¹, Wenbin Qian¹, Haitao Meng¹, Wenyuan Mai¹, Wenjun Yu¹, Weilai Xu¹, Lei Wang¹, Liping Mao¹, Renzhi Pei², Jie Jin¹

Affiliations

¹ Department of Hematology, Leukemia center, The First Affiliated Hospital of Zhejiang University, College of Medicine; Key Laboratory of Hematopoietic Malignancies in Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China.
² Department of Hematology, the Ningbo Yinzhou People's Hospital, Zhejiang, People's Republic of China.
³ Fujian Provincial Key Laboratory of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China.

PMID: 29862538
DOI: 10.1002/hon.2519

Abstract

Limited data was available for long-term follow-up in newly diagnosed acute promyelocytic leukemia (APL) patients treated with all-trans-retinoic acid (ATRA) plus intravenously arsenic trioxide (ATO)-based front-line therapy. The aim of this work was to retrospectively analyze the long-term survival rate and frequency of therapy-related myeloid neoplasia (t-MN) occurring in a large cohort of APL patients. A total of 760 newly diagnosed patients with APL between January 1999 and May 2016 were evaluated. The early death rate was 9.2% (70/760). Of the remaining 690 patients with complete remission, patients were grouped according to front-line regimens: ATRA plus ATO with or without chemotherapy (ATO group) and ATRA with chemotherapy (non-ATO group). The median duration of follow-up was 7.5 years (1.0-18.3 years). ATO group showed significant superior 10-year estimated relapse-free survival (RFS) up to 90.3% comparing with 65.5% in the non-ATO group (P < 0.0001). In addition, the 10-year estimated overall survival (OS) was 93.9% for patients in the ATO group and 89.1% for those in the non-ATO group (P = 0.03). In the subgroup analysis, the RFS rate was also higher in ATO group comparing with non-ATO group in both low-to-intermediate-risk (94.2% vs 64.6%, P < 0.0001) and high-risk subgroup (89.6% vs 74.7%, P = 0.04). Notably, the 3-year RFS and OS rates in the chemotherapy-free subgroup of the low-to-intermediate-risk patients (n = 88) were 100% and 100%, respectively. In the entire cohort, a total of 10 patients developed secondary malignant neoplasms, including 7 patients with therapy-related myeloid neoplasms (t-MN). The estimated 5-year cumulative incidence risk of t-MN in the ATO and non-ATO groups was 1.0% and 0.4%, respectively (P = 0.34). Thus, our data revealed that the long-term outcome of patients treated with ATRA plus ATO-based regimens was associated with continuing high efficacy in all Sanz risk patients with newly diagnosed APL.

Keywords: acute promyelocytic leukemia; arsenic trioxide; long-term survival; therapy-related myeloid neoplasms.