Prospective Study Of The Effect Of Enteral Nutrition On Nutritional Status And Side Effects Of Chemotherapy In Children With Acute Lymphoblastic Leukemia

Objective:The cure rate of acute lymphoblastic leukemia（ALL）in children has been significantly improved.However,the side effects during chemotherapy have affected the progress of chemotherapy and the quality of life of children,and have received more and more attention.Especially,the high incidence of malnutrition has a great impact on the quality of life,but it is easy to be ignored.Moreover,there is a lack of guidelines for nutritional support for children with ALL at present,and there are few studies on it.In this study,we provided enteral nutrition（short peptide type enteral nutrition preparation rich in medium chain triglycerides）to children with ALL,observed its influence on nutritional status and side effects of chemotherapy,and evaluated its effectiveness and safety in nutritional support,so as to provide clinical basis for the use of enteral nutrition intervention in children with ALL during chemotherapy.Methods:Children with ALL hospitalized for chemotherapy in the Affiliated Hospital of Qingdao University from December 2020 to March 2022 were selected as the research object.The patients were numbered according to the time sequence of enrollment,the singular was the observation group,and the even was the control group.The wishes of the children and their guardians were combined.The observation group received routine diet（low-fat diet during chemotherapy with asparaginase）and additional enteral nutrition（short peptide type enteral nutrition preparation rich in medium chain triglycerides）,and the control group received routine diet.Both groups were treated with chemotherapy according to the Chinese Children’s Cancer Group Study ALL 2020（CCCG-ALL-2020）.The chemotherapy stages observed in this study included induction remission therapy（1～4weeks,PVDL）,induction remission therapy（5～7 weeks,CAT）,early intensive therapy（CAT+）,1～2 High-dose Methotrexate(HDMTX_1-2)and 3～4 High-dose Methotrexate(HDMTX_3-4).In this study,60 cases were initially enrolled,including 53 cases before induction of remission,6 cases before HDMTX,1 child whose parents wanted to transfer out of the study before PVDL was completed,1 child whose parents wanted to withdraw during CAT（the stage completed before termination was included in the statistical analysis）,and a total of 59 cases were finally enrolled in the statistical analysis（30 cases in the observation group and 29 cases in the control group）.Among them,52 cases were enrolled since the initial diagnosis and completed the whole observation period（27 cases in the observation group and 25 cases in the control group）The following data were collected:1General information,including gender,age at first diagnosis and risk,2 Early treatment response,including minimal residual diseas（MRD）on days 19 and 46,3 Nutritional status,including height,weight,body mass index or BMI,total serum protein and serum albumin,4 Side effects of chemotherapy,including hypoproteinemia,hypoalbuminemia,liver function impairment,infection,severe infection and acute pancreatitis.The body measurement time point is before each chemotherapy stage.SPSS26.0 statistical software was used to analyze the data,metrology data are tested by t-test,counting data by chi-square test or Fisher exact probability method.P<0.05 indicated significant differences.Results:1.In this study,the incidence of malnutrition in children with ALL was 35.9%at the initial diagnosis,weight loss was 15.1%and obesity was 20.8%.2.Comparison of nutritional status:（1）In the observation group and control group,the incidence of malnutrition was 28.6%（8/28）and 44.0%（11/25）at the time of initial diagnosis,21.4%（6/28）and 32.0%（8/25）at PVDL,22.2%（6/27）and 20.0%（5/25）at CAT,14.3%（2/14）and 21.4%（3/14）at CAT+,17.2%（5/29）and 16.0%（4/25）at HDMTX_1-2,and 17.9%（5/28）and 20.7%（6/29）at HDMTX_3-4,respectively.There was no significant difference in the incidence of malnutrition between the two groups（P>0.05）.（2）After PVDL,the change of BMI Z score of the observation group was 0.453±1.642,while that of the control group was-0.403±1.031.The change of BMI Z score of the observation group was higher than that of the control group（t=2.243,P<0.05）,but no difference was found in other chemotherapy stages.52 children were initially admitted to the group and completed the 4th HDMTX treatment（27 cases in the observation group and25 cases in the control group）.At the end of the 4th HDMTX,the change of the BMI Z score of the observation group was 0.815±1.186,while that of the control group was-0.485±1.990.The difference was statistically significant（t=2.886,P<0.05）.（3）There was no significant difference in incidence of hypoproteinemia and hypoalbuminemia between the two groups（P>0.05）.The incidence of hypoproteinemia and hypoalbuminemia was 71.2%～81.5%and 8.8%～40.4%respectively.（4）The infusion of albumin accounted for 16.7%（5/30）in the observation group and41.4%（12/29）in the control group,which were lower in the observation group than in the control group,and the difference was statistically significant（P<0.05）.3.Comparison of liver function impairment:During PVDL,the incidence of liver function impairment（elevated ALT）in the observation group was lower than that in the control group,and the difference was statistically significant（²=4.093,P<0.05）.In other chemotherapy stages,there was no significant difference between the two groups（P>0.05）.4.Comparison of infection:（1）146 infections occurred in 2 groups,including respiratory infection,bloodstream infection,soft tissue infection of skin,digestive tract infection,urinary tract infection,central nervous system infection and unexplained infection,and mainly respiratory tract infection,accounting for 39.0%.（2）During PVDL,CAT,CAT+,HDMTX_1-2,HDMTX_3-4,the infection rates in the observation group were 75.0%（21/28）,59.3%（16/27）,42.9%（6/14）,41.4%（12/29）,25.0%（7/28）,and 88.0%（22/25）,80.0%（20/25）,71.4%（10/14）,40.0%（10/25）,27.6%（8/29）in the control group.There was no significant difference in the infection rate between 2 groups（P>0.05）.（3）The proportion of severe infection was 32.9%（48/146）in two groups,24.3%（17/70）in the observation group and 40.8%（31/76）in the control group.The proportion of severe infection in observation group was lower than that in control group（P<0.05）.5.There were 2 cases of acute pancreatitis in 2 group after the first application of asparaginase,1 cases in control group and 1 case in observation group.6.On the 46th day,25 cases（83.3%）of MRD were negative and 5 cases（16.7%）were positive in the observation group,and 26 cases（89.7%）were negative and 3 cases（10.3%）were positive in the control group.There was no significant difference between the two groups in MRD on the 46th day（P>0.05）.Conclusions:1.Children with acute lymphoblastic leukemia have a high incidence of malnutrition at the first diagnosis,including weight loss and obesity.They also had a higher incidence of malnutrition during chemotherapy.2.Enteral nutrition can improve the nutritional status of children with acute lymphoblastic leukemia in the early stage of chemotherapy,and long-term enteral nutrition can improve the final nutritional status of them.3.Enteral nutrition support can reduce the incidence of severe infection in children with acute lymphoblastic leukemia.4.Short peptide type enteral nutrition preparation rich in medium chain triglycerides is safe and effective for enteral nutrition intervention in children with acute lymphoblastic leukemia.