Analysis Of The Causes Of Early Death In Acute Promyelocytic Leukemia

BackgroundAcute promyelocytic leukemia(APL)is a special type of acute myeloid leukemia(AML),accounting for 10%-15%%of acute myeloid leukemia,with an incidence rate of approximately ten million,with a median age of 44 years.Due to various causes,leukemic cells lose control of proliferation,differentiation and apoptosis,thus inhibiting normal hematopoiesis of bone marrow.In APL patients,abnormal promyelocytes in peripheral blood and bone marrow increased,and characteristic chromosome translocation t(15;17)(q22;Q12)appeared,forming PML-rara fusion gene.Its protein products lead to the arrest of differentiation and apoptosis of promyelocytes in bone marrow,resulting in anemia,low blood platelets and coagulation function,leading to serious bleeding tendency,infection and other serious complications,which is very easy to progress Disseminated intravascular coagulation(DIC).In the past two decades,the progress of treatment has significantly improved the prognosis of APL.With the use of all trans retinoic acid(ATRA)and arsenic trioxide,APL has become the most curable subtype of AML.The PML gene(PML)on chromosome 15 was translocated with the retinoic acid receptor alpha(RAR α)on chromosome 17.The PML rar a fusion gene can encode PML rar a fusion protein.All trans retinoic acid(ATRA)can specifically target the rar a part of the fusion gene,release the transcriptional inhibition of the gene,and make the promyelocytes differentiate into mature stage.Arsenic trioxide can specifically target rar a part of the fusion gene,induce the differentiation and apoptosis of early immature granulocytes,and improve the healing rate of APL.However,according to statistics at home and abroad,the early mortality rate has not been significantly reduced.Bleeding,differentiation syndrome,DIC,infection and other factors are still the main causes of early death of APL.In recent years,with the development of molecular biology and the progress of diagnosis and treatment,the chemotherapy scheme has been optimized gradually.At present,we use platelet transfusion,cold precipitation,plasma,fibrinogen and other means for coagulation abnormality and bleeding,but the risk of early bleeding is still worthy of further study to reduce early mortality.At present,although the induced remission rate of APL is significantly increased,the side effects of retinoic acid and arsenic can not be ignored,and the early death is still worthy of our attention.At present,the domestic and foreign guidelines are not targeted to reduce the early mortality of APL,such as the application timing and dosage of anthracycline chemotherapy drugs.Whether we need to further improve the good in symptomatic support treatment and primary disease treatment is also worthy of further study.ObjectiveBy analyzing the clinical data of the first admission of the newly diagnosed patients with acute promyelocytic leukemia,the factors that may be related to the early death were collected and analyzed to explore the causes and influencing factors of the early death of the disease,so as to provide an objective basis for reducing the early death rate.MethodsA total of 282 newly diagnosed APL patients admitted to our hematology department from January 2000 to September 2019 were analyzed.Among them,27 patients died early(ED),255 patients died not early(NED)after treatment.The early death rate was 9.6%.The nested retrospective case analysis and statistics method was used to make a retrospective study according to 1:4-5 random proportion.Collect the data related to the disease,mainly including basic data,laboratory test results,bone marrow test,treatment plan.SPSS was used to analyze the highest and lowest values of blood routine indexes(WBC,Hb,PLT,neutrophil absolute value)before and during treatment,the highest and lowest values of coagulation indexes(PT,APTT,FIB,D-dimer)before and during treatment,the highest and lowest values in LDH treatment,whether DIC and chemotherapy were combined in treatment,laboratory test results(AST,ALT,Cr,uric acid,BUN,BNP),The results of bone marrow cytology(the proportion of primordial cells in bone marrow,the degree of myelodysplasia),leukemia immunotyping(CD34+,CD56+,HLA-DR+,FLT3)and patients’ treatment delay were analyzed by logistic regression.Results1.Fatal bleeding accounted for 81.5%(22/27)of early death patients,which was the main cause of early death in APL patients.2.Single factor screening:age,leukocyte level before and during treatment,hemoglobin level during treatment,platelet level at the highest level,Pt level before and during treatment,APTT level during treatment,D-dimer level at the highest level,fibrinogen level at the highest and lowest level during treatment,DIC in treatment,risk stratification,types of chemotherapy drugs,whether or not in treatment There were significant differences in dexamethasone(DEX),bone marrow cells,uric acid and ALB between the patients without early death(P<0.05)3.Multiple factor analysis showed that the age was more than 40 years old(P=0.018),leukocyte was more than 30×10^9/L(P=0.016),Pt was prolonged for 3 s during the treatment(P=0.003),APTT was prolonged for 10 s(P=0.004)were independent risk factor of early death.Conclusions1.The main cause of early death of APL is fatal hemorrhage.2.Over 40 years old,high leukocyte,prolonged Pt and APTT are independent risk factors for early death in patients with acute promyelocytic leukemia.The early monitoring and clinical intervention should be carried out in patients over 40 years old with APL.The patients with hyperleukocytosis were treated with leucocyte reduction in time.The monitoring of coagulation function is very important in the process of induction.Patients with DIC tendency should actively correct coagulation indicators.