Clinical Characteristics And Prognosis Analysis Of Childhood ALL With KRAS Mutation

[Objective]KRAS mutation is the focus of research in childhood ALL,but its effects in childhood ALL are not clear.In order to give support for clinical risk classification and prognosis,this study examined the mutation rate of the KRAS gene in children’s ALL.Also,the clinical features of children with KRAS mutation,event-free survival(EFS),and overall survival(OS)were further examined.[Methods]By retrospective analysis,data on 513 untreated ALL children were gathered from the Department of Hematology and Oncology of Kunming Children’s Hospital between January 2019 and December 2022,of which 56 children qualified for inclusion.Analysis was done on the relationship between the KRAS mutation and clinical traits.The clinical characteristics included age,gender,ethnicity,clinical presentation,hepatosplenomegaly,peripheral blood image at first diagnosis,proportion of naive cells at first diagnosis,minimal residual disease(MRD)at day 15 and day 33,risk stratification,chromosome number,immunologic classification,abnormal genes and adverse reactions.Furtherly,the prognosis of KRAS mutation in children with ALL was explored.[Results]1.Genetic mutation rate:The KRAS mutation rate among children with ALL was 17.2%(88/513),and in B-ALL,the KRAS mutation rate was 20.3%(88/434).2.Related clinical features:The majority of KRAS-mutant patients were between the ages of 1 and 10 years old,and the proportion of patients older than 10 years old in the KRAS-mutant group was substantially lower than that in the KRAS-unmutated group(P<0.05).There were 29 male cases,which was slightly more than the number of female cases(27).Median value of platelets at initial diagnosis were 37.5x10~9/L,which was significantly lower than group without KRAS mutation(P<0.05).The median value of white blood cell(WBC)at initial diagnosis was 6.59x10~9/L and there were 51 cases with the number of WBC lower than 50x10~9/L.Patients with KRAS mutation were all belong to B-ALL(100%),which was significantly different from the proportion of B-ALL among those without KRAS mutation(83.9%,P<0.05).There were 0 cases(0%)in the low-risk group,49 cases(87.5%)in the medium-risk group,and 7 cases(12.5%)in the high-risk group in the KRAS mutation group.The proportion of patients in the medium-risk group was significantly higher in the KRAS mutation group than in the negative group(P<0.05).Three occurrences of extramedullary invasion,including one involving the central nervous system and two involving the bones,emerged among 56 patients with the KRAS mutation,although there was no statistically significant difference when compared to the group without the mutation(P>0.05).In the group with the KRAS mutation,the percentage of moderate or severe hepatomegaly was 50%,which was substantially greater than the percentage in the group without the KRAS mutation(30.4%,P<0.05).3.Response to treatment:On day 15,the group with the KRAS mutation had a considerably greater positive MRD rate than the control group(P<0.05).On day 33,the positive rate of MRD was somewhat greater in the KRAS mutation group than in the control group,but the difference was not statistically significant(P>0.05).4.Recurrence rate,mortality and survival rate:one case with KRAS mutation was excluded from follow-up during chemotherapy,thus the remaining 55 cases were included in survival analysis.The recurrence rate(0%)and mortality rate(3.6%)were lower than those in KRAS(-)group(5.5%and 7.3%).Chi-square test was used to compare the recurrence rate and mortality rate,and the difference was not statistically significant(P=0.079 and P=0.401,respectively).The 2-year event-free survival(EFS)and 2-year overall survival(OS)rates of patients with KRAS mutation were both 92.9%,which were higher than those in the negative group(2-year EFS and 2-year OS rates were 84.8%and 87.9%,respectively).Log Rank test was used to compare The 2-year event-free survival(EFS)and 2-year overall survival(OS)rates,and the difference was not statistically significant(P=0.341 and P=0.524,respectively).5.Analysis of prognostic factors:Gender,age,nationality,risk stratification,WBC,chromosome,15th day MRD,33rd day MRD,liver enlargement and spleen enlargement of patients with KRAS mutation had no significant impact on EFS and OS(P>0.05).The incidence of high white blood cells was low in ALL patients in KRAS(-)group,and the effects of WBC count on EFS and OS at initial diagnosis were statistically significant(P<0.05),which may indicate that low WBC count at initial diagnosis may affect EFS and OS.[Conclusion]1.The KRAS mutation rate was not unusual in ALL patients.2.The KRAS mutation are more common in children under 10 years of age and initial platelet count is lower.3.Patients with KRAS mutation were more likely to develop in B-ALL.The risk stratification was mainly moderate risk and complete remission rate at day 15 was low.4.Patients with KRAS mutation is one of the poor prognostic indicators in B-ALL patients.