| Objective:To study the positive incidence of fusion gene ETV6/RUNX1 in children's ALL,its clinical characteristics in children's ALL and its effect on survival and prognosis,and to provide clinical research data for children's ALL risk classification and treatment options,so as to achieve targeted treatment.Methods:A total of 550 children with newly diagnosed ALL in the Department of Hematology/Oncology of Kunming Children's Hospital(affiliated Children's Hospital of Kunming Medical University/Yunnan Children's Medical Center)from January 2015 to December 2019 were retrospectively analyzed.ETV6/RUNX1 fusion gene was detected by reverse transcriptase polymerase chain reaction(RT-PCR)in order to explore the clinical characteristics and survival prognosis of ALL children with ETV6/RUNX1(+).65 ALL children with ETV6/RUNX1(+)and no other gene positive were selected as the experimental group,and 65 ALL children with ETV6/RUNX1(-)and without other gene positive in Kunming Children's Hospital were randomly selected as the control group.Wilcoxon rank sum test was used to compare the difference of peripheral blood infantile,WBC,Hb and PLT between ETV6/RUNX1(+)group and ETV6/RUNX1(-)group.Pearson chi-square test was used to compare the differences in sex,age,nationality,immune type,risk stratification,Peripheral blood leukocyte count,recurrence rate,mortality,the 19th day MRD and the hormones response on the fifth day between ETV6/RUNX1(+)group and ETV6/RUNX1(-)group.Fisher accurate test was used to compare the difference of hepatosplenomegaly and MRD on the 46th day between ETV6/RUNX1(+)group and ETV6/RUNX1(-)group.Kaplan-Meieranalysis was used to draw EFS and OS survival curves of ETV6/RUNX1(+)and ETV6/RUNX1(-)groups.Log-ranktest was used to compare the differences of EFS rate and OS rate among clinical factors such as sex,age,nationality,Peripheral blood leukocyte count,immune classification,risk stratification and so on.Univariate COX regression was used to screen the included clinical factors,and multivariate COX regression was used to analyze the risk factors.Results:1.Positive rate and related clinical data:? ALL detected ETV6-RUNX1(+)in 74 of 550 children,with a positive rate of 13.4%(74/550),of which 9 cases were combined with other gene positive(6 cases with IKZF1 gene deletion mutation,2 cases with MLL gene positive,1 case with MYC gene positive);?There were 45 children with ALL in the ETV6/RUNX1(+)low-risk group(69.2%),18 cases in the medium-risk group(27.7%),and 2 cases in the high-risk group(3.1%).The proportion of the low-risk group was the most;? The age in the ETV6/RUNX1(+)group was older than that in the ETV6/RUNX1(-)group,and the difference was statistically significant(Z=-2.219,P<0.05),and most of the ages were between 2 and 10 years old,and there was no age less than 2 years old;?The proportion of white blood cells?50×109/L was significantly lower in the ETV6/RUNX1(+)group than in the ETV6/RUNX1(-)group,and the difference was statistically significant(x 2=6.923,P<0.05);?ETV6/RUNX1(+)group is all B series ALL;?In the ETV6/RUNX1(+)group,there was no case of central nervous system infiltration at the first diagnosis.2.Response to treatment:the positive rate of MRD in ETV6/RUNX1(+)group was lower than that in ETV6/RUNX1(-)group on the 19th day,and the rate of good hormone response in ETV6/RUNX1(+)group was higher than that in ETV6/RUNX1(-)group.3.Recurrence,mortality and survival rate:of the 65 children with ETV6/RUNX1(+),3 cases lost follow-up during chemotherapy,1 case gave up treatment,and the remaining 61 cases were included in survival analysis.The recurrence rate(3.3%)and mortality rate(4.9%)in the ETV6/RUNX1(+)group were lower than those in the ETV6/RUNX1(-)group(11.1%14.3%),However,there was no statistical significance in comparing the recurrence rate and mortality rate between the two groups by Pearson chi-square test(P=0.182,P=0.078).The 2-year EFS rate and OS rate of ALL children in the ETV6/RUNX1(+)group were 93.4%and 95.1%respectively,and the 4-year EFS rate and OS rate were 91.8%and 95.1%respectively,which were higher than those in the ETV6/RUNX1(-)group(2-year EFS rate and OS rate were 82.5%and 87.3%respectively,4-year EFS rate and OS rate were 82.5%and 85.7%respectively).However,Kaplan-Meier analysis was used to draw EFS and OS survival curves of ETV6/RUNX1(+)and ETV6/RUNX1(-)groups,and there was no significant difference between EFS and OS survival curves by log-rank test(P=0.110,P=0.077).4.Analysis of prognostic factors:There was no significant effect of sex,age group,nationality,immune type,risk stratification,peripheral blood leukocyte count,hepatosplenomegaly and hormone response on ALL EFS rate and OS rate in children with ETV6/RUNX1(+)(P>0.05and P>0.2),The effect of MRD on EFS rate on the 19th day was analyzed(P<0.2),The effect of hormone response on the rate of EFS in ETV6/RUNX1(-)group was statistically significant(P<0.05).So,It is speculated that the value of MRD and hormone response on the 19th day may be effective indicators for monitoring prognosis.5.To further verify the clinical value of MRD and hormone response of ALL in children:there were 130cases of ALL in ETV6/RUNX1(+)group and ETV6/RUNX1(-)group.The analysis of MRD and hormone response on the 19th day showed that the EFS rate and OS rate in MRD positive group were lower than those in MRD negative group,and the difference was statistically significant(P<0.05).The EFS rate in poor hormone response group was significantly lower than that in good hormone response group(P<0.05).Conclusion:1.Most of the ALL children with ETV6/RUNX1(+)are accompanied by good clinical features,such as leukocyte<50 x 109/L,age between 2 and 10 years old,B-line lymphocyte phenotype,high bone marrow remission rate,good hormone response and soon.2.ETV6/RUNX1(+)was not found in children under 2 years old in our study.3.The proportion of ALL children with ETV6/RUNX1(+)was 69.2%in low-risk group,27.7%in medium-risk group and 3.1%in high-risk group,suggesting that most of the risk stratification in ETV6/RUNX1(+)group was low risk.4.In this study,the recurrence rate of ALL children with ETV6/RUNX1(+)is 3.3%,which is lower than that reported in China.The 2-and 4-year EFS rate and OS rate can reach 90%-95%.The analysis shows that ETV6/RUNX1 fusion gene is a biological marker with good prognosis in children's ALL.5.In this study,there were two cases of recurrence in children with ALL in ETV6/RUNX1(+)group,one in very early stage and one in early stage,and there was no late recurrence,which was not consistent with that reported in related literature.It is necessary to enlarge the sample size and increase the follow-up time to further verify that the recurrence of ALL children with ETV6/RUNX1(+)occurs in the late stage6.The positive rate of ETV6/RUNX1 in children with ALL is 13.4%,which is lower than that reported in China,and higher than that in foreign countries such as India.The positive rate of ETV6/RUNX1 may be related to race.7.The detection of MRD and hormone test during the treatment of ALL in children are of great significance in terms of prognosis. |
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