Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia.

Abstract

All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) combination-based therapy has benefitted newly diagnosed acute promyelocytic leukemia (APL) in short-term studies, but the long-term efficacy and safety remained unclear. From April 2001, we have followed 85 patients administrated ATRA/ATO with a median follow-up of 70 months. Eighty patients (94.1%) entered complete remission (CR). Kaplan-Meier estimates of the 5-year event-free survival (EFS) and overall survival (OS) for all patients were 89.2% +/- 3.4% and 91.7% +/- 3.0%, respectively, and the 5-year relapse-free survival (RFS) and OS for patients who achieved CR (n = 80) were 94.8% +/- 2.5% and 97.4% +/- 1.8%, respectively. Upon ATRA/ATO, prognosis was not influenced by initial white blood cell count, distinct PML-RARalpha types, or FLT3 mutations. The toxicity profile was mild and reversible. No secondary carcinoma was observed, and 24 months after the last dose of ATRA/ATO, patients had urine arsenic concentrations well below the safety limit. These results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for de novo APL.

• Authors: Jiong Hu, Yuan-Fang Liu, Chuan-Feng Wu, Fang Xu, Zhi-Xiang Shen, Yong-Mei Zhu, Jun-Min Li, Wei Tang, Wei-Li Zhao, Wen Wu, Hui-Ping Sun, Qiu-Sheng Chen, Bing Chen, Guang-Biao Zhou, Arthur Zelent, Samuel Waxman, Zhen-Yi Wang, Sai-Juan Chen, Zhu Chen
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 9 Pg. 3342-7 (Mar 03 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19225113 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AQP9 protein, human
• Aquaporins
• Arsenicals
• Oncogene Proteins, Fusion
• Oxides
• promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
• Tretinoin
• Arsenic Trioxide

Topics

• Aquaporins (genetics, metabolism)
• Arsenic Trioxide
• Arsenicals (adverse effects, therapeutic use)
• Gene Expression Regulation, Leukemic (drug effects)
• Leukemia, Promyelocytic, Acute (diagnosis, drug therapy, genetics, metabolism)
• Oncogene Proteins, Fusion (genetics, metabolism)
• Oxides (adverse effects, therapeutic use)
• Prognosis
• Survival Rate
• Time Factors
• Tretinoin (adverse effects, therapeutic use)