SUBSCRIBE
Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (9): 801-808.doi: 10.3736/jcim20090901

• Systematic Review •     Next Articles

Efficacy of arsenic trioxide for acute promyelocytic leukemia: A systematic review and meta-analysis

Shuang-nian Xua,Jie-ping Chena,Jian-ping Liub,Yun Xiab   

  1. a Center for Hematology,Southwest Hospital, Third Military Medical University, Chongqing 400038, China
    b Center for Evidence-Based Medicine,Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2009-06-04 Accepted:2009-08-04 Online:2009-09-20 Published:2009-09-15
  • Contact: Jie-ping Chen, Jian-ping Liu E-mail:chenjpxn@yahoo.com.cn;jianping_l@hotmail.com

RichHTML

2

PDF (PC)

88

Like

Objective

To systematically review the efficacy and safety of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL).
Methods

The Cochrane Library (Issue 1, 2009), Cochrane Central Register of Controlled Trials (from 1970 to January 2009), MEDLINE (from 1978 to October 2008), EMBASE (from 1950 to March 2009), Chinese Biological Medical Literature Database (from 1978 to December 2008), China National Knowledge Infrastructure (CNKI, from 1994 to December 2008), and China Medical Academic Conference Database (from 1994 to December 2008) were electronically searched. We also searched the Meta-Register of controlled trials, Conference Proceedings of American Society of Hematology (from 1946 to December 2008) and Conference Proceedings of American Society of Clinical Oncology (from 1946 to December 2008) on the internet for grey literature. The related journals in the library of Third Military Medical University were hand-searched. The randomized controlled trials (RCTs) of ATO in treatment of APL were included. We adopted complete remission, overall survival rate, disease free survival rate, time to complete remission, relapse rate, mortality and adverse reactions as outcome indicators. Data were entered and analyzed with the Cochrane review manager software 5.0 (RevMan 5.0).
Results

After merger of the included trials, five eligible RCTs with 328 cases were included. All the RCTs focused on the comparison of all-trans retinoic acid (ATRA) plus ATO regimen with ATRA monotherapy. Meta-analysis showed that the effect indexes for time to complete remission, two-year disease free survival rate, relapse rate, incidence of edema and incidence rate of QT interval prolongation were –1.20 [–1.68, –0.72], 8.64 [1.66,45.00], 0.21 [0.09,0.47], 4.16 [1.46,11.79] and 22.10 [2.75,177.49], respectively. The influences on other outcome indicators such as complete remission and leukocytosis were statistically non-significant.
Conclusion

ATO can prolong disease free survival and reduce the time to complete remission and relapse rate of newly diagnosed APL patients, and increase the incidence of edema and prolongation of corrected QT interval during the treatment. Due to limitation of the included trials, this conclusion needs to be validated by further studies.

Key words: Arsenic trioxide, Leukemia, Promyelocytic, Acute, Randomized controlled trial, Systematic review, Meta-analysis

Figure 1

Flow diagram of literature searching and screening"

Table 1

Basic characteristics of the included studies"

Study Cases* Male/Female△ Median age (years)▲ White blood cell count ($\bar{x}$±s, 109/L) Treatment program
ATO (–) group ATO (+) group ATO (–) group ATO (+) group ATO (–) group ATO (+) group ATO (–) group ATO (+) group ATO (–) group ATO (+) group
Shen et al[14] 20 21 12/8 9/12 30.5 34 Did not report Did not report ATRA 25 mg/(m2·d) ATO 0.16 mg/(kg·d); ATRA 25 mg/(m2·d)
Su et al [15] 30 40 12/18 18/22 31 37.2 11.9±21.5 15.7±20.6 ATRA 25 mg/(m2·d) ATO 0.16 mg/(kg·d); ATRA 30-40 mg/d
Ren et al [16] 52 43 30/22 23/20 32 34 11.9±21.5 13.6±23.9 ATRA 25 mg/(m2·d) ATO 10 mg/d; ATRA 25 mg/(m2·d)
Yang et al[17] 11 15 4/7 5/10 41 39 Did not report Did not report ATRA 30-60 mg/d ATO 10 mg/d; ATRA 30-60 mg/d
Zhou et al [9,10,11,12,13] 48 48 30/18 28/20 23 21 7.8±3.0 8.2±2.5 ATO 0.16 mg/(kg·d), routine intravenous infusion (30-40 drops per minute) ATO 0.16 mg/(kg·d), continuous slow intravenous infusion (8 drops per minute)

Figure 2

Bias risk from the included trials"

Figure 3

Summary of the bias risk from the included trials"

Figure 4

Effects of adding ATO on complete remission rate of APL patients"

Figure 5

Effects of adding ATO on the relapse rate of APL patients"

[1] Lu DP. Therapeutics of leukemia[M]. Beijing: Science Press, 1992: 152
陆道培 . 白血病治疗学[M]. 北京: 科学出版社, 1992: 152
[2] Ribeiro RC, Rego E . Management of APL in developing countries: epidemiology, challenges and opportunities for international collaboration[J]. Hematology Am Soc Hematol Educ Program, 2006: 162-168
[3] Ribeiro RC, Rego E . Acute promyelocytic leukemia: from highly fatal to highly curable[J]. Blood, 2008,111(5):2505-2515
doi: 10.1182/blood-2007-07-102798
[4] Kelaidi C, Ades L, Chevret S, Sanz M, Guerci A , Thomas X, de Botton S, Raffoux E, Rayon C, Fegueux N, Bordessoule D, Rigal-Huguet F, Link H, Stoppa A, Vekhoff A, Meyer-Monard S, Castaigne S, Dombret H, Degos L, Fenaux P. Late first relapses in APL treated with all-trans-retinoic acid- and anthracycline-based chemotherapy: The European APL group experience(APL 91 and APL 93 trials)[J]. Leukemia, 2006,20(5):905-907
doi: 10.1038/sj.leu.2404158
[5] Zhang TD, Li YS . Clinical analysis and experimental study of Ailing Ⅰ in treatment of acute promyelocytic leukemia[J]. Zhong Xi Yi Jie He Za Zhi, 1984,4(1):19-20
张亭栋, 李元善 . 癌灵Ⅰ号治疗急性粒细胞白血病临床分析及实验研究[J]. 中西医结合杂志, 1984,4(1):19-20
[6] Ma J . Review of progress on treatment of acute promyelocytic leukemia with arsenic trioxide[J]. Guo Ji Shu Xue Yu Xue Ye Xue Za Zhi, 2007,30(3):210-213
doi: 10.3760/cma.j.issn.1673-419X.2007.03.004
马军 . 三氧化二砷治疗急性早幼粒细胞白血病的回顾及进展[J]. 国际输血和血液学杂志, 2007,30(3):210-213
doi: 10.3760/cma.j.issn.1673-419X.2007.03.004
[7] Higgins JPT , Green S . Cochrane Handbook for Systematic Reviews of Interventions Version 5. 0. 0 [updated February] 2008[M]. Oxford: The Cochrane Library,2008
[8] Tierney JF, Stewart LA, Ghersi D, Burdett S , Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis[J]. Trials, 2007, 8: 16
doi: 10.1186/1745-6215-8-16 pmid: 1920534
[9] Zhou J, Meng R, Wang Y, Yang BF . Clinical observation and following up of two administration methods of arsenic trioxide in treatment of acute promyelocytic leukemia[J]. Zhonghua Yi Xue Za Zhi, 2004,84(5):405-408
doi: 10.3760/j:issn:0376-2491.2004.05.015
周晋, 孟然, 王艳, 杨宝峰 . 三氧化二砷不同给药方法治疗急性粒细胞白血病的临床观察和随访[J]. 中华医学杂志, 2004,84(5):405-408
doi: 10.3760/j:issn:0376-2491.2004.05.015
[10] Zhou J, Meng R, Yang BF . Comparing two arsenic trioxide administration methods in APL therapy[J]. Chin Med J (Engl), 2004,117(9):1411-1413
[11] Zhou J, Meng R, Sui XH, Meng L, Jia J, Yang BF . Effects of administration styles of arsenic trioxide on intracellular arsenic concentration, cell differentiation and apoptosis[J]. Haematologica, 2005,90(9):1277-1279
[12] Zhou J, Meng R, Sui XH, Meng L, Yang BF . Effects of arsenic trioxide administration styles on leukocytosis[J]. Chin Med Sci J, 2006,21(2):111-114
pmid: 16845799
[13] Zhou J, Meng R, Yang BF . Clinical effects of arsenic trioxide by slowing-intravenous infusion on acute promyelocyte leukemia[J]. Chin Med Sci J, 2005,20(2):137
[14] Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang ZY, Chen SJ, Chen Z . All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia[J]. Natl Acad Sci U S A, 2004,101(15):5328-5335
doi: 10.1073/pnas.0400053101
[15] Su XL, Xia WL . Clinical observation of all-trans retinoic acid and arsenic trioxide in treatment of newly diagnosed acute promyelocytic leukemia[J]. Ji Ceng Yi Xue Lun Tan, 2006,10(4):338-339
doi: 10.3969/j.issn.1672-1721.2006.07.030
苏秀连, 夏维林 . 维甲酸联合砷剂治疗初发APL的临床疗效观察[J]. 基层医学论坛, 2006,10(4):338-339
doi: 10.3969/j.issn.1672-1721.2006.07.030
[16] Ren JH, Lin FR, Guo XN, Wang Y, Zhang JN, Wang Y, Dong ZR . Clinical observation of all-trans retinoic acid, arsenic trioxide and chemotherapy in treating acute promyelocytic leukemia[J]. Zhonghua Xue Ye Xue Za Zhi, 2004,25(7):437-438
doi: 10.3760/j:issn:0253-2727.2004.07.016
任金海, 林凤茹, 郭晓楠, 王颖, 张静楠, 王艳, 董作仁 . 全反式维甲酸、三氧化二砷及联合化疗治疗急性早幼粒细胞白血病临床观察[J]. 中华血液学杂志, 2004,25(7):437-438
doi: 10.3760/j:issn:0253-2727.2004.07.016
[17] Yang EQ, Liu ZM, He C . Efficacy of all-trans retinoic acid and arsenic trioxide in treatment of newly diagnosed acute promyelocytic leukemia[J]. Bai Xue Bing Lin Ba Liu, 2006,15(3):216-217
杨恩芹, 刘志梅, 贺春 . 维a酸与亚砷酸联合治疗初发的急性早幼粒细胞白血病疗效分析[J]. 白血病·淋巴瘤, 2006,15(3):216-217
[18] Chen Z, Zhao WL, Shen ZX, Li JM, Chen SJ, Zhu J, Lallemand BV, Zhou J, Guillemin MC, Vitoux D, de The H. Arsenic trioxide and acute promyelocytic leukemia: clinical and biological[J]. Curr Top Microbiol Immunol, 2007, 313: 129-144
doi: 10.1007/978-3-540-34594-7_8 pmid: 17217042
[19] Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, Han ZG, Ni JH, Shi GY, Jia PM, Liu MM, He KL, Niu C, Ma J, Zhang P, Zhang TD, Paul P, Naoe T, Kitamura K, Miller W, Waxman S , Wang ZY, de The H, Chen SJ, Chen Z. Use of arsenic trioxide(As2O3) in the treatment of acute promyelocytic leukemia(APL): Ⅰ. As2O3 exerts dose-dependent dual effects on APL cells[J]. Blood, 1997,89(9):3345-3353
[20] Douer D, Tallman M . Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies[J]. J Clin Oncol, 2005,23(10):2396-2410
doi: 10.1200/JCO.2005.10.217 pmid: 15800332
[1] Sherman Gu, Arthur Yin Fan. Controversial conclusions from two randomized controlled trials for acupuncture's effects on polycystic ovary syndrome or in vitro fertilization support. Journal of Integrative Medicine, 2020, 18(2): 89-91.
[2] Gerli E.G. Herr, Fábio Goulart da Silva, Francisco José Cidral-Filho, Fabricia Petronilho, Lucinéia Gainski Danielski, Mariana Pereira de Souza Goldim, Afonso Shiguemi Inoue Salgado, Franciane Bobinski, Daniel Fernandes Martins, Eliane R. Winkelmann. Effects of the use of bioceramic wraps in patients with lower limb venous ulcers: A randomized double-blind placebo-controlled trial. Journal of Integrative Medicine, 2020, 18(1): 27-.
[3] Xin-yu Yue, Zhuo-qi Feng, Xi-yi Yu, Jia-min Hu, Xiao-Jing He, Shi Shu. Fire-needle acupuncture for upper limb spastic paralysis after stroke: Study protocol for a randomized controlled trial. Journal of Integrative Medicine, 2019, 17(3): 167-172.
[4] Ya-ru Huangfu, Wei Peng, Bao-jun Guo, Zhi-fu Shen, Li Li, Shi-wei, Liu, Hui Zheng, You-ping Hu. Effects of acupuncture in treating insomnia due to spleen-stomach disharmony syndrome and its influence on intestinal microbiome: Study protocol for a randomized controlled trial. Journal of Integrative Medicine, 2019, 17(3): 161-167.
[5] Pádraic J.Dunne, Julie Lynch, Lucia Prihodova, Caoimhe O'Leary, Atiyeh Ghoreyshi, Sharee A. Basdeo, Donal J.Cox, Rachel Breen, Ali Sheikhi, Áine Carroll, Cathal Walsh, Geraldine McMahon, Barry White. Burnout in the emergency department: Randomized controlled trial of an attention-based training program. Journal of Integrative Medicine, 2019, 17(3): 173-180.
[6] Jia Xu, Fu-qing Zhang, Jian Pei, Jun Ji . Acupuncture for migraine without aura: A systematic review and meta-analysis. Journal of Integrative Medicine, 2018, 16(5): 312-321.
[7] J.M. Oliver-Baxter, H.S. Whitford, D.A. Turnbull, M.J. Bond. Effects of vitamin supplementation on inflammatory markers and psychological wellbeing among distressed women: A randomized controlled trial. Journal of Integrative Medicine, 2018, 16(5): 322-328.
[8] Jeremiah Oshiomame Unuofin, Gloria Aderonke Otunola, Anthony Jide Afolayan. Evaluation of acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. in Wistar rats. Journal of Integrative Medicine, 2018, 16(5): 335-341.
[9] Parunkul Tungsukruthai, Preecha Nootim, Wiwan Worakunphanich, Nareerat Tabtong. Efficacy and safety of herbal steam bath in allergic rhinitis: A randomized controlled trial. Journal of Integrative Medicine, 2018, 16(1): 39-44.
[10] Zahra Hajmohammadi, Mojtaba Heydari, Majid Nimrouzi, Pouya Faridi, Mohammad Javad Zibaeenezhad, Gholamhossein Ranjbar Omrani, Mesbah Shams . Rhus coriaria L. increases serum apolipoprotein-A1 and high-density lipoprotein cholesterol levels: A double-blind placebo-controlled randomized clinical trial. Journal of Integrative Medicine, 2018, 16(1): 45-50.
[11] Laura Belland, Laura Rivera-Reyes, Ula Hwang. Using music to reduce anxiety among older adults in the emergency department: A randomized pilot study. Journal of Integrative Medicine, 2017, 15(6): 450-455.
[12] Hilal Yuksel, Yasemin Cayir, Zahide Kosan, Kenan Tastan. Effectiveness of breathing exercises during the second stage of labor on labor pain and duration: A randomized controlled trial. Journal of Integrative Medicine, 2017, 15(6): 456-461.
[13] Yoshiharu Motoo, Takashi Hakamatsuka, Nobuo Kawahara, Ichiro Arai, Kiichiro Tsutani. Standards of Reporting Kampo Products (STORK) in research articles. Journal of Integrative Medicine, 2017, 15(3): 182-185.
[14] Qian-wen Ma, Yong Tan. Effectiveness of co-treatment with traditional Chinese medicine and letrozole for polycystic ovary syndrome: A meta-analysis. Journal of Integrative Medicine, 2017, 15(2): 95-101.
[15] Maria T.Chao, AlexandraChang, SanjayReddy, James D.Harrison, JosephAcquah, MiriaToveg, TrilceSantana, Frederick M.Hecht. Adjunctive acupuncture for pain and symptom management in the inpatient setting: Protocol for a pilot hybrid effectiveness-implementation study. Journal of Integrative Medicine, 2016, 14(3): 228-238.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[2] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)". Journal of Chinese Integrative Medicine, 2008, 6(1): 15-21
[3] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[6] SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[7] A-gao Zhou, Yong Zhang, Gang Kui, De-Yun Kong, Hai-liang Ge, Qiu-hua Ren, Jia-rong Dong, Sheng Hong, Xu-ming Mao, Yin Wang, Hui-zheng Zhang, Shu-jun Wang. Influence of traditional Chinese compound recipes with different efficacy on body weight, tumor weight and immune function in H22 cancer-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 77-82
[8] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[9] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[10] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
Journal of Integrative Medicine, ISSN: 2095-4964 CN 31-2083/R
Copyright © Journal of Integrative Medicine
Powered by Beijing Magtech Co. Ltd
沪公网安备31010602003416号      沪ICP备18017633号-3