Analysis Of Clinical Characteristics Between JMML,CML And MDS

Objective:Juvenile myelomonocytic leukemia(JMML),myelodysplastic syndrome(MDS),and chronic myelogenous leukemia(CML)have similar clinical features and all have a low prevalence in children with a poor overall prognosis.The diagnosis of hematologic diseases in children currently relies on karyotype and gene mutation testing,but due to the limitations of knowledge,some cases cannot be diagnosed through testing,for example,25%of children with JMML have no known typical gene mutations associated with JMML,so it is difficult to distinguish them from other diseases in the early stages of the disease.Therefore,it is necessary to improve the understanding of the clinical features and laboratory tests of the three diseases,as well as the clinical differentiation from diseases with similar presentations.In this paper,we summarize the clinical characteristics of the three diseases in a single center and compare the three diseases in a comparative study to help physicians make a preliminary differential diagnosis from a clinical perspective,with the aim of providing a basis for future diagnosis and clinical practice.Methods:1.Case information:19 JMML,40 MDS,and 49 CML cases diagnosed in the First Affiliated Hospital of Zhengzhou University between January 2013 and December 2019 were selected as study subjects.Clinical presentation,laboratory tests,genetic mutations,survival status and factors influencing outcome were analyzed in the study.Three groups of data were compared for study.2.Statistical treatment:IBM SPSS Statistics 26.0 software was used for statistical analysis.Normality tests were performed on all data.Quantitative data with normal distribution were expressed as mean± standard deviation(x±s),and quantitative data with non-normal distribution were expressed as median and interquartile spacing[M(IQR:P25,P75)].Qualitative data were expressed as rates(%).The t-test was used for the analysis of variance of quantitative data,and the χ2 test was used for the analysis of variance of qualitative data.Kruskal-Wallis H test was used for comparison between multiple groups.The Nemenyi test was used for two-way comparisons.The Kaplan-Meier method was used for survival analysis.COX regression model was used for prognostic analysis.And p<0.05 was considered a statistically significant difference.Results:1.General information:The median age in the JMML group was 9 months(range 1.9 to 53.8 months).The median age in the MDS group was 85.4 months(range 11.8 to 159.4 months).The median age in the CML group was 101.2 months(range 3.3 to 164.6 months).Comparison of the three groups showed that children in the CML group had a greater age of onset than the JMML group(p<0.05).2.Clinical symptoms:Hepatosplenomegaly was present in all patients in the JMML group.The median degree of hepatomegaly was 4.5 cm(range 3-13 cm)and the median degree of splenomegaly was 5 cm(range 2～12 cm).Fever and pallor were present in 14 cases(73.7%),lymph node enlargement in 11 cases,skin rash in 3 cases,and diarrhea in 2 cases.In the CML group:splenomegaly in 47 cases(95.9%),the median degree of splenomegaly was 9 cm(range 0～17 cm),pallor in 41 cases,hepatomegaly in 21 cases,the median degree of hepatomegaly was 2 cm(range 1～8 cm),fever in 21 cases,lymph node enlargement in 20 cases,gastrointestinal symptoms in 12 cases,and petechiae in 8 cases.In the MDS group:28 cases(70%)with both fever and pallor,19 cases with bleeding symptoms,9 cases with hepatomegaly(range 0～8 cm),9 cases with enlarged lymph nodes,7 cases with splenomegaly(range 0～14 cm),and 5 cases with skin rash.The above results suggest that the children in the JMML group had mainly hepatosplenomegaly,fever,and pallor.The CML group had mainly splenomegaly and pallor.The MDS group had mainly fever,pallor,and bleeding symptoms.Comparison of the three groups showed that the degree of liver enlargement was JMML,CML,and MDS in descending order(p<0.05).The degree of splenomegaly was higher in both the CML and JMML groups than in the MDS group(p<0.05).3.Hematological indexes:19 children with JMML:WBC 37.3 ×109/L(IQR:15,64.1),Hb(92.3±11.6)g/L,PLT32×109/L(IQR:21,72),MONO 7.19×109/L,ChE(4.07 ± 2.13)kU/L,LDH 404 U/L(IQR:270,515.5).Patients in the JMML group had predominantly elevated leukocytes,mild anemia,thrombocytopenia and significantly elevated monocytes;CML group:WBC 228.5 X 109/L(IQR:81.35,470.3),Hb(87.9±11.6)g/L,PLT 360×109/L(IQR:195.5,598),MONO 2.45×109/L(IQR:1.25,4.55),ChE(5.65±1.75)kU/L,LDH 861 U/L(IQR:664,1086).Patients in the CML group were characterized by significantly elevated white blood cells and mild to moderate anemia;MDS group:WBC 5.77× 109/L(IQR:3.46,10.2),Hb(87.9±18)g/L,PLT 59.5×109/L(IQR:32.3,116.8);MONO 0.51×109/L(IQR:0.18,1.41),ChE(6.23±2.16)kU/L,LDH 363.3U/L(IQR:202,415).Patients in the MDS group were predominantly anemic and thrombocytopenic.Comparison of the three groups showed that WBC and PLT were higher in the CML group than in the other two groups.MONO was higher in the JMML group than in the CML group.ChE levels were higher in the CML group compared to the JMML group.LDH levels were higher in the CML group than in the other two groups(p<0.05).4.Cell morphology examination:The median percentage of peripheral blood blasts in 19 children with JMML was 0%,range 0%～6%.The median mature monocyte proportion was 21%.Bone marrow was hyperplastic or hyperactive in all patients.The median bone marrow blast was 1.2%,and the median mature monocyte in the bone marrow was 3.6%.Patients in the CML group had a median proportion of blasts in the bone marrow of 0%and a median proportion of mature monocytes in the bone marrow of 0%.The median proportion of peripheral blood blasts in the MDS group was 0%,and the median proportion of mature monocytes was 2.0%.The median proportion of primitive granulocytes in the bone marrow was 7.3%,and the median proportion of mature monocytes in the bone marrow was 1.6%.The percentage of monocytes in bone marrow was higher in the JMML group compared with the CML group(p<0.05),and the differences in the remaining indicators were not statistically significant.5.Cytogenetics and molecular biology examination:Karyotype analysis was performed in 7 of 19 children with JMML,and monosomy of chromosome 7 was found in 2(28.6%).Genetic testing for BCR/ABL1 fusions was negative in all 19 children.Mutations of JMML related genes were detected in 7 children,4 had mutations in KRAS(57.1%),2 in NF1(28.6%),and 1 in NRAS(14.3%).Karyotype analysis was performed in 24 of 40 children with MDS,including 10 with normal karyotype and 14(58.3%)with abnormal karyotype.Nine patients were tested for mutations in MDS associated genes,7 patients with MDS associated mutations,ASXL1,HOXll and WT1,Pig-a,CSF3R,SH2B3,TET2,SRSF2,U2AF1,and YARS2,respectively.BCR/ABL1 was positive in all CML children.6.Survival:In the JMML group,three patients died,two were alive,and 14 were lost to follow-up,with a median survival time of 2 months,range 1-34 months.The 1-year OS rate was 30.5%±12.4%.In the MDS group,3 patients were lost to follow-up,19 died,and 18 were alive,with a median survival time of 9.25 months and a 1-year OS rate of 70%±7.2%.Of the 9 patients in the CML group who were lost to follow-up,19 died and 21 were alive,with an overall median survival time of 32.1 months and an overall 1-year OS rate of 75%±6.8%.Children treated with imatinib had a median survival time of 39.8 months and a 1-year OS rate of 90.6%±5.2%.Contrasting the survival status of the three groups(p=0.01)showed that the JMML group had the shortest survival time.Comparing the three groups of survival situation(p=0.01),the results showed that the JMML group had the lowest survival rate.7.Cox regression analysis:Univariate COX analysis in the JMML group showed that age,lymph node enlargement,pale,cholinesterase level,monocytes greater than 10×109/L,and the age was greater than 2 years were risk factors affecting the survival of JMML patients(p<0.1).Multi-factor COX regression analysis showed that monocytes greater than 10×109/L was an independent risk factor affecting the prognosis of JMML patients(p=0.033),HR=3.936(95%CI:1.118-13.860).The differences of the remaining indicators on the prognosis were not statistically significant(p>0.05).COX regression analysis in the MDS and CML groups showed that the differences of all indicators on the prognosis were not statistically significant(p>0.05).Conclusions:1.The degree of leukocyte elevation and monocyte level in blood routine can help to make clinical differential diagnosis of the three groups of diseases.2.JMML often presents with moderate hepatosplenomegaly,CML mostly with severe splenomegaly,while hepatosplenomegaly is not obvious in the MDS group.The degree of hepatosplenomegaly should be carefully measured in clinical work for subsequent differentiation.3.Monocytes greater than 1×109/L are an independent risk factor affecting the prognosis of JMML patients.4.Positive gene mutation test results are useful in diagnosing and identifying the three diseases.However,it is important to note that some mutation results are present in multiple diseases.In such cases,the diagnosis should be confirmed after careful identification of the clinical features.