Occurrence And Risk Factors Of Diabetes In Children With Acute Lymphoblastic Leukemia Under Chemotherapy Combinated With Asparaginase

Objective: To analyze the clinical features and risk factors of drug-induced diabetes after chemotherapy with asparaginase(L-asparaginase and pegaspargase)in children with acute lymphoblastic leukemia(ALL),and analyze the relationship between the prognosis of diabetes and leukemia chemotherapy and to treat ALL.The use of asparaginase in children with drug-induced diabetes provides a diagnostic and therapeutic reference.Methods: We retrospectively analyzed 87 children with confirmed ALL who were hospitalized in the pediatric3 wards from May 2015 to April 2018.The age,gender,body mass index(BMI),and Leukemia clinical risk stratification(low risk,moderate risk,high risk),33 days post-chemotherapy remission,follow-up survival,use of asparaginase,Monitoring of randomized blood glucose before and after asparaginase chemotherapy and level of albumin(ALB)after 1 week(5 days to 8 days)after chemotherapy,risk factors for asparaginase-associated diabetes were analyzed,and the association between diabetes and ALL prognosis was analyzed.Result:1.A total of 87 children were enrolled in the study.37(42.5%)of drug-induced diabetes mellitus were treated during the post-chemotherapy period with two different aspartame synthesizers(37.7%).Clinical features of 37 children with drug-induced diabetes: median Age 4.0(3.3 years,8.0 years),median BMI 15.00(14.00,16.35),male to female ratio: 1.18:1,with typical symptoms of diabetes(Polydipsia,polyphagia,polyuria,weight loss)In 4 patients(10.8%),the average peak blood glucose level was 16.9 mmol/L,the duration of hyperglycemia was 2 to 30 days,and the average time was 6.8 days.,The median time was 4 days(3 days and 8 days).14 patients were treated with insulin(37.8)%),The average course of treatment with insulin was 11.5 days,and the average amount of insulin was 0.7 U/kg.d.Of the 87 children with chemotherapy,one had diabetic ketoacidosis(1.1%)and 4 had acute pancreatitis(4.6%).The level of albumin in the drug-induced diabetic group was lower than that in the non-diabetic group(P<0.05).Among children with ALL who were treated with asparaginase chemotherapy,the incidence of drug-induced diabetes was higher in middle-risk and high-risk children then the low-risk,and the difference was statistically significant(P<0.05).2,According to the use of asparaginase treatment course calculation,combined with L-asparaginase(L-asparaginase,L-ASP)chemotherapy has 91 courses,the occurrence of drug-induced diabetes 28 course of treatment(30.77%),combined with Pegaspargase(PEG-ASP)there were 92 courses of chemotherapy,and 18 courses of drug-induced diabetes occurred(19.57%),but there was no significant difference between the two groups(P>0.05).3.The incidence of diabetes during the use of asparaginase combined chemotherapy in children with ALL chemotherapy in each chemotherapy stage: induction remission(33.33%),early intensive phase(0),consolidation phase(12.64%),delayed intensive phase(7.14%),The difference between the groups was statistically significant(?2=46.32,P<0.001).4.Whether or not drug-induced diabetes occurred as a dependent variable,binary logistic regression analysis with age ? 10 years,gender,BMI,risk stratification,and immunophenotype as independent variables,the results showed that Age,gender,BMI,immunophenotype were not the influencing factors of drug-induced diabetes(P>0.05),the risk of drug-induced diabetes in non-low-risk patients(medium and high risk)was 3.003 times that of low-risk children(?=1.100,OR=3.003,95% CI: 1.085 to 8.315).5.Using death as the end point,age,sex,BMI,immunophenotype,risk stratification,and diabetes as independent variables were included in the COX regression model for analysis.The results showed that Age,gender,BMI,immunophenotype,risk stratification are not risk factors for death in children with ALL(P>0.05),the risk of drug-induced diabetes in children who are middle-risk and high-risk is 3.003 times that of low-risk children(?=2.312,OR=10.098,95% CI:1.258~81.094).CONCLUSION:1.The incidence of drug-induced diabetes during the ALL childhood asparaginase combination chemotherapy was higher(42.5%).Asparaginase combined with chemotherapy-induced diabetes during chemotherapy lacks the typical clinical manifestations,most do not require insulin therapy,,clinical identification difficulties,need to strengthen monitoring of blood glucose.2.There was no significant difference in the incidence of drug-induced diabetes between children with ALL and L-ASP or PEG-ASP.3.Drug-induced diabetes during asparaginase-combination chemotherapy is more likely to occur during the remission phase of induction of ALL chemotherapy.4.During asparaginase combined with chemotherapy,children with moderate to high risk of ALL are more likely to develop drug-induced diabetes.5.Drug-induced diabetes mellitus in ALL children may be one of the risk factors for the prognosis of children.