Comparative Study Of All-trans Retinoic Acid 25mg/m~2 And 45mg/m~2 As The First Induction Regimen For The Treatment Of Acute Promyelocytic Leukemia

Background:Acute promyelocytic leukemia（APL）accounts for approximately 10%of acute myeloid leukemia,which French-American-British classification is M3.The regimen based on all-trans retinoic acid（ATRA）and arsenic trioxide（ATO）has become the first-line induction regimen for patients of APL,which improves the complete remission（CR）rate and long-term survival rate increased to 90%.However,in the real clinical setting,the early mortality of APL patients,especially high-risk patients,is still high.How to further reduce the early death rate and improve the survival rate of APL patients in clinical practice is still an urgent problem to be solved.However,there are two main dosages of ATRA used in the induction regimen of APL patients,and there is no relevant study demonstrating the difference between the two dosages of ATRA.This study mainly retrospective analyzed the data of APL patients in our center in the real-world setting and compared the efficacy between patients administered dosages of ATRA of 25 mg/m~2/day and 45 mg/m~2/day,with 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.Methods:A total of 161 consecutive newly diagnosed APL patients at the First Affiliated Hospital of University of Science and Technology of China（Anhui Provincial Hospital）from January 2010 to December 2018 were included in this retrospective analysis.132 patients were treated with an ATRA 25 mg/m~2/d-based regimen（ATRA-25mg group）,while 29 patients were treated with an ATRA 45 mg/m~2/d-based regimen（ATRA-45mg group）.Results:After the first induction treatment,108 patients（81.8%）in the ATRA-25mg group and 28 patients（96.6%）in the ATRA-45mg group achieved morphological CR（p=0.049）.For the whole APL patients,the 5-year cumulative incidence of relapse（CIR）rate,5-year overall survival（OS）rate and 5-year event-free survival（EFS）rate were16.6%（95%CI:19.7-24.9%）,84.0%（95%CI:76.1-89.4%）and 72.5%（95%CI:63.0-79.9%）in the ATRA-25mg group,and the 5-year CIR rate,5-year OS rate and5-year EFS rate were 0%（p=0.046）,96.6%（95%CI:78.0-99.5%）（p=0.095）and 96.6%（95%CI:78.0-99.5%）（p=0.019）in the ATRA-45mg group.For low-intermediate-risk patients,the 5-year CIR rate,5-year OS rate and 5-year EFS rate were 12.9%（95%CI:6.2-22.1%）,87.9（95%CI:78.4-93.4%）and 78.6%（95%CI:67.5-86.3%）in the ATRA-25mg group,and the 5-year CIR rate,5-year OS rate and 5-year EFS rate were0%（p=0.187）,94.4%（95%CI:66.6-99.2%）（p=0.526）and 94.4%（95%CI:66.6-99.2%）（p=0.228）in the ATRA-45mg group.For high-risk patients,the 5-year CIR rate,5-year OS rate and 5-year EFS rate were 27%（95%CI:10.4-46.8%）,75.6%（95%CI:59.4-86.1%）and 58.1%（95%CI:38.6-73.4%）in the ATRA-25mg group,and the 5-year CIR rate,5-year OS rate and 5-year EFS rate were 0%（p=0.099）,100%（p=0.081）and100%（p=0.025）in the ATRA-45mg group.Conclusion:This study demonstrates that for APL patients（especially high-risk patients）,the induction regimen based on ATRA 45mg/m~2/day could more easily lead to morphological CR and can achieve a higher long-term survival rate and a lower disease relapse rate than ATRA 25mg/m~2/day without increasing the risk of differentiation syndrome and coagulation dysfunction.The induction regimen based on ATRA45mg/m~2/day and ATO could be the first choice to use for high-risk patients,and it is recommended to add anthracyclines to the induction regimen to quickly reduce leukocytes.