Clinical Characteristics And Prognosis Survival Of 106chinese Adults With Acute Myeloid Leukemia

Background:Acute myeloid leukemia(AML)is a group of malignant clonal blood diseases in which hematopoietic stem cell differentiation is arrested in the early stages of different myeloid development.The main clinical manifestations are infection,anemia and hemorrhage.The incidence rate is increasing year by year and the mortality rate is high because of the factors such as population aging,environmental pollution,food safety and so on。Molecular biology and cytogenetics are the pathogenesis of AML,and the expression of key genes is associated with the prognosis of AML.Currently,systematic detection of gene expression levels and cytogenetics in AML is still lacking.Objective:The clinical characteristics and prognosis of newly diagnosed Chinese adult AML patients were discussed by FLT3-ITD,NPM1,CEBPA,C-kit/D816 V four gene mutations and cytogenetics detection,which provided a theoretical basis for adult AML treatment and prognosis.Methods:Retrospectively collected the initial AML adult patients(except M3)from January 1,2015 to December 31,2017 that was diagnosed in our hospital by bone marrow morphological examination to confirm that the bone marrow image conformed to the FAB classification(M0-M7),We ruled out treatment-related AML and previously had a clear history of the blood system and excludes untreated patients.Collect about 5 ml of bone marrow at the time of initial diagnosis for FLT3-ITD,NPM1,CEBPA,C-kit/D816 V mutations and karyotype detection.We also collected general clinical information such as gender,age,and laboratory tests,bone marrow image after induction of remission and so on.Overall survival was recorded mainly through the outpatient and telephone follow-up,we use IBM SPSS 24.0 statistical analysis software for data analysis,P < 0.05 was statistically significant,counting data were described by composition ratio,the comparison between groups was performed by chi-square test,the measurement data was described by median and interquartile range M(Q),the comparison between groups was performed by rank sum test.Results:1、 A total of 106 patients,64 males and 42 females,with an age range of19-82 years,the average age is 54 years old,Median age 51 years old,M0 and M6 have no patient,M1 three cases,M2 forty one patients,M4 eighteen patients,M5 thirty two patients,M7 1 patient,8 cases of AML which could not be classified,1 case of gastric granulocyte sarcoma and 2 cases of acute mixed cell leukemia.Age above 60 have 37 patients,accounting for 34.9%(37/106);2、Results of each gene mutation and karyotype:We divided one and have only one mutation into A1(FLT3),A2(CEBPA),A3(NPM1),and A4(C-kit)groups,and combined with two gene mutations and above into group B,without mutation were C group.Group C contains 37 patients,accounting for 34.95%(37/106).The mutation rates of the each genes are(including 2 or more mutations):the detection rate of FLT3-ITD was 22.6%(24/106),the CEBPA was 32%(34/106),which was the highest among the four genes.,the mutation rate of c-kit /D816 v was 9.4%(10/106),NPM1 was 17%(18/106).Fifty-four patients had normal karyotype,accounting for 50.9%,and 49.1% had abnormal karyotype.The general condition and clinical characteristics of different gene mutation groups were analyzed,the results showed that the karyotypes were statistically different in different gene mutation groups(χ2=76.452,P<0.001),and CEBPA mutations were more likely to accompany with cytogenetic abnormalities.There was no statistical difference in the distribution of leukemia typing(P=0.902),gender(P=0.490),and age(P=0.890)in different genomes;3、At the time of initial diagnosis,the NPM1 mutation had a higher white blood cell level(P=0.034),and the C-kit/D816 V mutation had a higher ratio of bone marrow original cells(P=0.014),both are not associated with the prognosis of AML;4.、 In the elderly population aged ≥60 years,the distribution of karyotypes in each group was statistically different(χ2=34,331, P<0.001),older people are more likely to combine two or more mutations and are expressed in abnormal karyotypes;5、By the end of follow-up,a total of 39 patients died,accounting for36.8%.Among them,11 died of bleeding and infection before the end of the first chemotherapy,median follow-up of 18.7 months,4 people lost follow-up,the remaining 63 patients survived from onset to follow-up date.The distribution of karyotypes in different gene mutation groups was statistically different in the death group,(χ2=25.797,P<0.001).The number of deaths of each gene mutation is 12 in FLT3-ITD(12/24),12 in CEBPA(12/34),6 in NPM1(6/18),and 5 in C-KIT/D816V(5)/10).The median survival of the different gene mutations in the deceased patients was statistically significant(P=0.018),and the C-KIT/D816 V single mutation had the longest survival,with a median survival of 30 months.,followed by the 12-month median survival of the NPM1 mutation and the9-month median survival of the CEBPA mutation,FLT3-ITD single mutation has the shortest survival period of 7 months.There was no statistically difference in survival among the patients still alive and among the patients over 60 years of age in the different gene mutation groups(P = 0.077 and 0.355,respectively).Multiple comparisons showed that the median survival time was correlated between groups A1 and A4,A1 and B,A1 and C,A3 and A4,A2 and A4,A2 and B.Conclusion:1、The CEBPA gene mutation is the most common type of mutation in Chinese adult AML.It is more easily expressed in abnormal karyotypes, which is a intermediate prognosis in the Chinese population.The mutation rate of NPM1 is low in Chinese population,NPM1 mutation has a high white blood cell count at the time of initial diagnosis,its prognosis is similar to CEBPA.2、Older people are more likely to combine two or more mutations and are expressed in abnormal karyotypes.3、The C-KIT/D816 V mutation has a low mutation rate in the Chinese population and has a high proportion of bone marrow blast cells at the time of initial diagnosis,its median survival time is longer,the mortality rate is higher,and the overall prognosis is poor.FLT3-ITD mutations have higher mortality and shorter survival time and are independent prognostic factors for AML;4 、 Genetic mutations and cytogenetics alone may not be sufficient to assess the prognosis of AML patients in the Chinese population.Further testing of more AML-related genes is needed to determine the prognosis and establish a more comprehensive genome.