title: 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.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine and Institute of Health Science, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Hu
authors.forename: Yuan-Fang
authors.initials: YF
authors.lastname: Liu
authors.forename: Chuan-Feng
authors.initials: CF
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Shen
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhu
authors.forename: Jun-Min
authors.initials: JM
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhao
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Sun
authors.forename: Qiu-Sheng
authors.initials: QS
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Guang-Biao
authors.initials: GB
authors.lastname: Zhou
authors.forename: Arthur
authors.initials: A
authors.lastname: Zelent
authors.forename: Samuel
authors.initials: S
authors.lastname: Waxman
authors.forename: Zhen-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
mesh_terms: D020346:Aquaporins / Q000235:genetics / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects* / Q000627:therapeutic use*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000009:adverse effects* / Q000627:therapeutic use*; D011379:Prognosis; D015996:Survival Rate; D013997:Time Factors; D014212:Tretinoin / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: C109669:AQP9 protein, human; D020346:Aquaporins; D001152:Arsenicals; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D000077237:Arsenic Trioxide