Correlative Study Of Clinical Features And Prognosis Of Pediatric AML Patients With C-KIT Mutation

Objective:The abnormal expression of proto-oncogene C-KIT(C-KIT)is considered to be associated with poor prognosis in acute myeloid leukemia.To Provide new evidence and guidance for clinical treatment and prognosis assessment of Pediatric AML Patients,we did a retrospective analysis of the gene mutations and clinical features of the patients,and trying to find the correlation between C-KIT mutation and clinical features and prognosis.Methods:Selected 103 patients with untreated AML who were admitted to the Department of Hematology of Kunming Children's Hospital from September 2015 to February 2018.First,recording the detection rate and mutation type of C-KIT,age of on set,gender,karyotype,immunophenotype,the blood routine and the blast cell ratio of bone marrow at the initial diagnosis,adverse reactions and remission rate after chemotherapy and disease-free survival.Second,dividing them into positive and negative groups of C-KIT mutation,and compare them.Results:1.C-KIT mutations was detected in 8 cases among the 103 cases(about 7.8%of the total),all of them were exon 17 mutations(D816V mutations),and 95 cases of C-KIT mutation-negative(about 92.2%of the total).2.There were 54 males and 49 females of the 103 cases.Among the C-KIT-positive infants,2 were male(25.0%)and 6 were female(75.0%);the median age of C-KIT positive children was approximately 9.3.At the age of 8.7 to 13.3 years,the median age of C-KIT negative children was approximately 8.5 years(0.7 to 16.3 years).Use chi-square test to compare the patients,it was found that there was no significant difference in gender and age between the positive and negative(P>0.05).3.There were 4 M2,3 M4,and 1 M5 in the 8 cases with C-KIT mutations.None of the patients with C-KIT mutation in the other FAB types.Use Fisher's exact test to compare the patients,it was found that there was no significant difference in the distribution of C-KIT on different FAB types(P>0.05).4.The average WBC count in peripheral blood at the initial diagnosis was 69.52�22.91�109/L in children with C-KIT mutation,and was 33.32�42.50�109/L in the negative.The average of hemoglobin in peripheral blood at the initial diagnosis was 73.13�10.20g/L in C-KIT mutation-positive children,and 82.28�17.40g/L in the negative.The average platelet counts in peripheral blood at the initial diagnosis was 34.13�20.36�109/L in C-KIT mutation-positive children,and 57.35�70.28�109/L in the negative.The average percentage of immature cells in peripheral blood at the initial diagnosis was 45.2 � 22.3%in children with C-KIT mutations and 36.2 � 27.8%in those with negative results.The average percentage of bone marrow naive cells at the initial diagnosis was 64.2�23.7%in C-KIT mutation-positive children and 57.6�20.6%for negative children.Use independent sample T test to compare the patients,it was found that there was a significant difference in peripheral blood WBC between the positive and negative(P<0.05),but there were no significant differences among other indicators between the positive group and the negative,such as the percentage of immature cells in peripheral blood,HGB,PLT,percentage of myeloblasts in bone marrow at the time of their first diagnosis(P>0.05).5.Only 1 case of hepatotoxicity occurred after chemotherapy,and no obvious nephrotoxicity was observed in children.All patients had different degrees of myelosuppression.Use independent sample T test to compare the patients with liver function,renal function and bone marrow suppression after chemotherapy,it was found that there was no significant difference in those indicators between the positive and negative(P>0.05).6.After the first course of induction chemotherapy,3 patients with C-KIT mutation were relieved with a remission rate of 37.5%;and after the second course of induction chemotherapy,6 patients were relieved with a remission rate of 75.0%.After the first course of induction chemotherapy,76 patients without C-KIT mutation were relieved with a remission rate of 80%;and after the second course of induction chemotherapy,4 patients were relieved with a remission rate of 88.4%.Use chi-square test to compare the patients,it was found that the remission rate of the first course of patients with C-KIT mutation was significantly lower than that of the negative group(P<0.05),but there was no significant difference in the remission rate of the second course between the positive and negative(P>0.05).7.11 patients were dead in 103,with a mortality rate of 10.6%.The main causes of death were severe infection after myelosuppression,severe bleeding,and abandonment of treatment.Only 1 patient relapsed after complete remission with a recurrence rate of 0.97%.Use chi-square test to compare the patients,it was found that there was no significant difference in remission rate,recurrence rate,and mortality rate between the positive and negative(P>0.05).8.The average DFS of children with C-KIT mutations was 18.75�3.77 months,while the average DFS of C-KIT-negative children was 26.73�0.73 months.Using Kaplan-Meier doing the survival analysis.It was found that DFS in children with C-KIT mutation was significantly lower than that in negative children(P<0.05).Conclusion(s):1.There were 8 patients who had the mutation of C-KIT,and it was about 7.8%of the total.There were 8 patients who had the mutation of C-KIT,and it was about 7.8%of the total.The detection rate is close to the result reported in the study of Chongqing area in 2016(7.2%),but it is lower than the result in the study of Beijing area in the same year(12.3%).2.In this study,8 cases of C-KIT mutations were all D816V mutations.3.There was no significant relationship between C-KIT mutation and gender.4.There was no significant relationship between C-KIT mutation and age.5.The C-KIT mutation is mainly detected in the M2 type and M4 type of FAB classification,occasionally in the M5 type.Its distribution in different FAB types had no significant statistical significance.6 There was a significant difference in peripheral blood WBC between the positive and negative.But there were no statistically significance in the other blood routine indicators and the percentage of immature cells in the peripheral blood and the percentage of myeloblasts in bone marrow between the positive and negative.7.There was no significant difference in the toxic reaction after receiving chemotherapy between the positive and negative.8.The remission rate of the first course and DFS of patients with C-KIT mutation was obviously lower than that of the negative group,but the remission rate of the second course between the positive group and the negative group has no statistical difference.The result may suggesting C-KIT was associated with a better prognosis than adult AML.