All-trans retinoic acid 45 mg/m2 is superior to 25 mg/m2 as the first induction regimen for the treatment of acute promyelocytic leukaemia: a retrospective analysis in a real-world clinical setting
Authors: Xinhui Zhang, Shanglong Feng, Jin Xu, Na Zhao, Xing Hu, Li Zhou, Juan Tong, Lei Xue, Lei Zhang, Yongsheng Han, Xingbing Wang, Liangquan Geng, Xiaoyu Zhu, Baolin Tang, Huilan Liu, Weibo Zhu, Xiaoyan Cai, Xin Liu, Zimin Sun, Changcheng Zheng
Journal: Blood Cancer Journal (2021)

Dear Editor,Acute promyelocytic leukaemia (APL) is a distinctive type of acute myeloid leukaemia (AML), accounting for approximately 10% of AML 1 .All-trans retinoic acid (ATRA) has been used to treat APL in large well-designed clinical trials, which showed that the CR rate and longterm survival increased to 90% based on ATRA combined with arsenic, and the risk of early mortality during induction was only 2.5%~5% 2-4 .However, in the realworld clinical setting, early mortality is still high, with a range of 17-21.8% 4-8.At present, there are two main doses of ATRA used in the world.In most haematologyoncology centres in Europe and the United States, the dosage of ATRA is 45 mg/m 2 /day, while the recommended dosage in China is 25 mg/m 2 /day 9-11 ; both of them have good clinical effects.However, there is no relevant study demonstrating the differences between the two dosages of ATRA.To further clarify whether there is any difference in the clinical efficacy of the two dosages of ATRA for APL, we retrospectively analysed the data of APL patients in our centre in the real-world clinical setting and compared the efficacy between patients administered a dosage of ATRA of 25 mg/m 2 /day (ATRA-25 mg) and those administered a dosage of ATRA of 45 mg/m 2 /day (ATRA-45 mg), with a focus on the occurrence of differentiation syndrome, early death, disease relapse and long-term survival, to provide references for further improving the clinical efficacy of APL.This study protocol was approved by the ethics committee of Anhui Provincial Hospital and was conducted in accordance with the Declaration of Helsinki.All patients received oral ATRA (a daily divided oral dose of 25 mg/m 2 or 45 mg/m 2 ) with or without arsenic trioxide (ATO) (a daily intravenous dose of 0.16 mg/kg) until CR.From January 2010 to December 2018, a total of 161 patients with newly diagnosed APL presented to our hospital; 132 patients were treated with an ATRA 25 mg/m 2 /day-based regimen (ATRA-25 mg group), while 29 patients were treated with an ATRA 45 mg/m 2 / day-based regimen (ATRA-45 mg group).Ninety patients also received ATO (ATRA plus ATO), including 62 patients in the ATRA-25 mg group and 28 patients in the ATRA-45 mg group (Supplementary Table 1S).Chemotherapy with idarubicin 8-12 mg/m 2 / day or daunorubicin 45-60 mg/m 2 /day for 3-4 days was added for high-risk patients, and for low-risk or intermediate-risk patients when necessary (especially for patients with WBC increasing more than 5 × 10 9 /L).Once diagnosed with differentiation syndrome 12-14 , dexamethasone at a dose of 10 mg twice daily was immediately initiated until symptoms improved.The main clinical characteristics of these patients at the first diagnosis are summarised in Table 1.Based on the Sanz risk score 15 , 41 patients (31.1%) had high-risk disease and 91 patients (68.9%) had low-or intermediate-risk