The Clinical Features And Prognostic Analysis Of High-risk Acute Promyelocytic Leukemia

Background:Acute promyelocytic leukemia(APL)is a kind of acute myeloid leukemia(AML),which with a specific gene and a special type of chromosome karyotype change,accounted for about 10-15% of the AML and more than 90% are adults.There are more than 90% of APL patients can be detected with t(15;17)(q22;Q21)chromosomal translocations which forms the PML-RARa fusion gene.The clinical manifestations of APL is serious and progress rapidly,and the characteristic of the disease is extensive and severe bleeding and diffuse intravascular coagulation(DIC),which was the highest of mortality,the shortest survival time among AML.In recent years,due to the application of retinoic acid(ATRA)and arsenic acid(ATO),the mortality and recurrence rate of the disease has been significantly reduced,which has become a curable malignant blood disease.Nevertheless,there are 5% to 10% of patients with initial treatment died early in induction therapy,and some patients relapsed after induction,mainly leukocyte(WBC)or greater than 50 x 109/L.At present,high white blood cell count is still the main reason and independent risk factors for survival of patients.Objective :To investigate the clinical features and outcomes of high-risk acute promyelocytic leukemia.Methods:A retrospective analysis was conducted to compare the clinical characteristics and prognosis of 72 high-risk APL patients and 173 low and intermedia-risk patients from January 2012 to January 2018,who were treated in the First Affiliated Hospital of ZhengZhou university.The induction treatment are given ATRA,ATO and anthracycline-based induction therapy or cytarabine,then give 3 periods of treatment to consolidate after CR and maintenance treatment are sequential give ATRA,ATO and different chemotherapy regimens,methotrexate(MTX)and 6-mercaptopurine(6 MP).Giving platelet transfusion,frozen plasma,cryoprecipitate blood products to them who has bleeding tendency or DIC.Using SPSS17.0 statistical software for analysis of two groups of patients with complete remission rate(CR),early mortality,5-year overall survival(OS),5 years without disease rate(DFS),recurrence rate and incidence of central nervous system leukemia(CNSL).Result:High-risk and low and intermedia-risk patients has no statistical difference in age,sex(P=0.456;P=0.875).The initial platelet counts of high-risk APL are significantly lower than that of low and intermedia-risk group(P=0.01).If PLT < 40 x 109 / L is the critical value,the proportion are 76.4%(55/72)and 58.4%(101/173)in the high risk and low and intermedia-risk groups,and the difference is statistically significant(P=0.008).The high-risk group often accompanied by additional chromosome abnormality and FLT3-ITD mutation(P=0.013;P<0.001).High-risk group than low and intermedia-risk has a higher incidence of DIC(6.9% to 1.7%,P<0.001),the early death(ED)rate(13.9% to 2.9%,P=0.001)and lower complete remission(CR)rate(83.3% to 94.8%,P=0.003).However,the CR rate do not have difference if the ED patients were excluded(96.8% to 97.6%,P=0.721).The 5 years estimated disease free survival(DFS)and 5 years estimated overall survival(OS)of high-rish group lower than that of low and intermedia-risk groups(72.6% to 89.6%,P=0.046;82.3% to 94.8%,P=0.002),but the former has a higher incidence of central nervous system(CNSL)relapse(8.3% to 2.9%,P=0.047)..Induction therapy are given ATRA+ATO+anthracycline+cytarabine and increase the number of intrathecal injection of medicine can reduce the high-risk group of early mortality and incidence of CNSL.Conclusion:1.High-risk group of APL has higher ED rate and recurrence rate,the prognosis is poor.2.Patients at high risk should start the treatment of ATRA+ATO+ anthracycline + cytidine regimen as soon as possible,and the application of glucocorticoid to prevent DS can reduce its early mortality.3.Prolong the maintenance treatment and appropriately increase the number of intrathecal injection times to prevent the recurrence and the occurrence of CNSL of high-risk group may be improving the survival time of the prognosis.4.Mutations of FLT3-ITD may not have significant adverse effects on prognosis of patients with high risk APL.