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

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 Z Zelent, Samuel Waxman, Zhen Yi Wang, Sai Juan Chen, Zhu Chen

Research output: Contribution to journalArticle

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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-RARα 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.

Original languageEnglish (US)
Pages (from-to)3342-3347
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number9
DOIs
StatePublished - Mar 3 2009
Externally publishedYes

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Acute Promyelocytic Leukemia
Tretinoin
Safety
Survival
Therapeutics
Kaplan-Meier Estimate
Arsenic
Leukocyte Count
Disease-Free Survival
arsenic trioxide
Urine
Carcinoma
Recurrence
Mutation

Keywords

  • 5-year EFS
  • 5-year OS
  • Arsenic retention
  • Combination therapy
  • Residual disease

ASJC Scopus subject areas

  • General

Cite this

Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. / Hu, Jiong; Liu, Yuan Fang; Wu, Chuan Feng; Xu, Fang; Shen, Zhi Xiang; Zhu, Yong Mei; Li, Jun Min; Tang, Wei; Zhao, Wei Li; Wu, Wen; Sun, Hui Ping; Chen, Qiu Sheng; Chen, Bing; Zhou, Guang Biao; Zelent, Arthur Z; Waxman, Samuel; Wang, Zhen Yi; Chen, Sai Juan; Chen, Zhu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 9, 03.03.2009, p. 3342-3347.

Research output: Contribution to journalArticle

Hu, J, Liu, YF, Wu, CF, Xu, F, Shen, ZX, Zhu, YM, Li, JM, Tang, W, Zhao, WL, Wu, W, Sun, HP, Chen, QS, Chen, B, Zhou, GB, Zelent, AZ, Waxman, S, Wang, ZY, Chen, SJ & Chen, Z 2009, 'Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 9, pp. 3342-3347. https://doi.org/10.1073/pnas.0813280106
Hu, Jiong ; Liu, Yuan Fang ; Wu, Chuan Feng ; Xu, Fang ; Shen, Zhi Xiang ; Zhu, Yong Mei ; Li, Jun Min ; Tang, Wei ; Zhao, Wei Li ; Wu, Wen ; Sun, Hui Ping ; Chen, Qiu Sheng ; Chen, Bing ; Zhou, Guang Biao ; Zelent, Arthur Z ; Waxman, Samuel ; Wang, Zhen Yi ; Chen, Sai Juan ; Chen, Zhu. / Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 9. pp. 3342-3347.
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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-RARα 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.",
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T1 - Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia

AU - Hu, Jiong

AU - Liu, Yuan Fang

AU - Wu, Chuan Feng

AU - Xu, Fang

AU - Shen, Zhi Xiang

AU - Zhu, Yong Mei

AU - Li, Jun Min

AU - Tang, Wei

AU - Zhao, Wei Li

AU - Wu, Wen

AU - Sun, Hui Ping

AU - Chen, Qiu Sheng

AU - Chen, Bing

AU - Zhou, Guang Biao

AU - Zelent, Arthur Z

AU - Waxman, Samuel

AU - Wang, Zhen Yi

AU - Chen, Sai Juan

AU - Chen, Zhu

PY - 2009/3/3

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N2 - 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-RARα 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.

AB - 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-RARα 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.

KW - 5-year EFS

KW - 5-year OS

KW - Arsenic retention

KW - Combination therapy

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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