Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study

Author:

Zheng Huyong1234ORCID,Jiang Hui5,Hu Shaoyan6ORCID,Liao Ning7,Shen Diying8,Tian Xin9,Hao Guoping10,Jin Runming11,Li Jianxin12,Fang Yongjun13,Ju Xiuli14,Liu Ansheng15,Wang Ningling16,Zhai Xiaowen17,Zhu Jiashi5,Hu Qun18,Li Limin19,Liu Wei20,Sun Lirong21,Wang Li22,Dai Yunpeng23,Feng Xiaoqin24,Li Fu25,Liang Hui26,Luo Xinhui27,Yan Mei28,Yin Qingning29,Chen Yan30,Han Yueqin31,Qu Lijun32,Tao Yanling33,Gao Hui34,He Zhixu35,Lin Limin36,Luo Jixia37,Pan Kaili38,Zhang Jingrong39,Zhang Rong40,Zhou Min41,Zhang Yuanyuan1234,Wang Linya1234,Zhang Ruidong1234,Xiao Peifang6,Ling Yayun7,Peng Xiaoxia42,Peng Yaguang42,Wang Tianyou1234,

Affiliation:

1. Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing, China

2. National Key Discipline of Pediatrics (Capital Medical University), Beijing, China

3. Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China

4. Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China

5. Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China

6. Children's Hospital of Soochow University, Suzhou, China

7. The First Affiliated Hospital of Guangxi Medical University, Nanning, China

8. The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China

9. Kunming Children's Hospital, Kunming, China

10. Children's Hospital of Shanxi, Shanxi, China

11. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

12. Wuhan Children's Hospital, Wuhan, China

13. Children's Hospital of Nanjing Medical University, Nanjing, China

14. Qilu Hospital of Shandong University, Jinan, China

15. Xi’an Children's Hospital, Xi'an, China

16. The Second Hospital of Anhui Medical University, Hefei, China

17. Children's Hospital of Fudan University, Shanghai, China

18. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

19. The First Affiliated Hospital, Harbin Medical University, Harbin, China

20. Zhengzhou Children's Hospital, Zhengzhou, China

21. The Affiliated Hospital of Qingdao University, Qingdao, China

22. Hebei Children's Hospital, Hebei, China

23. Shandong Provincial Hospital, Jinan, China

24. Nanfang Hospital, South Medical University, Guangzhou, China

25. Qilu Children's Hospital of Shandong University, Jinan, China

26. Qingdao Women and Children's Hospital, Qingdao, China

27. Children's Hospital of Xinjiang Uygur Autonomous Region, Ürümqi, China

28. The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China

29. Women Children Hospital of Qing Hai, Xining, China

30. Affiliated Hospital of Zunyi Medical University/Guizhou Provincial Children's Hospital, Zunyi, China

31. Liaocheng Children's Hospital, Liaocheng, China

32. Anhui Provincial Children's Hospital, Hefei, China

33. The Affiliated Hospital of Jining Medical University, Jining, China

34. Dalian Children's Hospital, Dalian, China

35. The Affiliated Hospital of Guizhou Medical University, Guiyang, China

36. The Second Affiliated Hospital of Shantou University Medical College, Shantou, China

37. Children's Hospital of Kaifeng City, Kaifeng City, China

38. Northwest Women's and Children's Hospital, Xi'an, China

39. Guiyang Children's Hospital, Guiyang, China

40. Sichuan Provincial People's Hospital, Chengdu, China

41. Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China

42. Center for Clinical Epidemiology and Evidence-Based Medicine, Beijing Children's Hospital, Capital Medical University, Beijing, China

Abstract

PURPOSE Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group ( P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group ( P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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