Risk Factors And Clinical Characteristics Analysis Of Central Nervous System Complications In Children With Acute Leukemia

ObjectiveThe purpose of this study is to explore the risk factors of central nervous system complications（CNSC）in children with acute leukemia（AL）during induction therapy,and summarize the clinical characteristics of CNSC to detect high-risk children with CNSC early and deal with them timely and effectively.Method30 children with AL who developed CNSC during the induced remission period in the Department of Pediatric Hematology of the First Hospital of Jilin University from March 2017 to September 2022 were collected as a case group,and 60 children with AL but without CNSC who were randomly selected within the samehospitalization period were used as the control group.Collect and summarize the general data,positive signs,leukemia classification,risk grouping,blood routine,lactate dehydrogenase（LDH）,C-reactive protein（CRP）,tumor lysis,geneticcharacteristics,bone marrow morphology and minimal residual disease（MRD）at the end of induction therapy in order to analyze risk factors of CNSC in children with AL and the influence of CNSC on the efficacy of remission.The clinical characteristics such as the disease type,time of occurrence,clinical manifestations,and treatmentprogress of CNSC in the case group were also collected and summarized.Results1.One-way ANOVA of AL with CNSC suggested statistical differences between groups in leukemia risk grouping,whether age was≤6 years and whether white blood cell count was>100×10⁹/L were present（P<0.05）.There was no statistical differences between gender,leukemia immunophenotyping,absolute neutrophil value,hemoglobin,platelets,LDH,large liver,spleen and lymph nodes,CRP and tumor lysis syndrome（TLS）（P>0.05）.2.The risk classification of leukemia,the total number of white blood cells（more than 100×10⁹/L）,age（≤6 years old）are further analyzed by multi-factor Logistic regression.The result showed that the increased risk level,age≤6 years old were independent risk factors for the occurrence of CNSC.3.Excluding acute promyelocytic leukemia（APL）,the comparison of unfavorable genetic features between the two groups suggested that unfavorable genetic features would increase the risk of CNSC in children with AL.In the CNSC group,there were9 children with unfavorable genetic characteristics,of which 4 cases（44.44%）had IKZF1 deletion,2 cases（22.22%）had MLL-AF4 fusion gene,1 case（11.11%）had BCR-ABL1 fusion gene,and 1 case（11.11%）had RUNX1 mutation,1 case（11.11%）had C-KIT mutation.4.According to the time of occurrence of CNSC,CNSC of 10 cases（33.33%）in30 children occurred before chemotherapy,8 cases（26.67%）occurred within 7 days after chemotherapy,and 12 cases（40.00%）occurred within 8-45 days after chemotherapy.5.According to the clinical manifestations of CNSC,9 cases（30.00%）had seizures,8 cases（26.67%）had headache,8 cases（26.67%）had no abnormal clinical manifestations,6 cases（20.00%）had nausea and vomiting,5 cases（16.67%）had disturbance of consciousness,3 cases（10.00%）had dizziness,3 cases（10.00%）had fever,and 1 case（3.33%）had limb pain.6.According to the types of diseases involved in CNSC,in the CNSC group,there were 12 cases（40.00%）of cerebrovascular diseases,9 cases（30.00%）of central nervous system leukemia（CNSL）,8 cases（26.67%）of intracranial infection,7 cases（23.33%）of epilepsy,4 cases（13.33%）of brain atrophy,3 cases（10.00%）of brain/spinal cord space occupying,1 case（3.33%）of white matter lesions,and 1 case（3.33%）of subdural effusion.Among the 12 children with cerebrovascular diseases,there were 8 cases of intracranial hemorrhage（66.67%）,2 cases of acute cerebral infarction（16.67%）,1 case of acute cerebral infarction with intracranial hemorrhage（8.33%）,and 1 case of intracranial hemorrhage with venous sinus thrombosis（8.33%）.Among the 8 cases of intracranial infection,4 cases（50.00%）were positive for cerebrospinal fluid pathogens,including human herpesvirus type 4 and 7,streptococcus pneumoniae,oral streptococcus,streptococcus mitis,1 case（12.50%）was positive for pseudomonas aeruginosa in blood pathogens,and the other three cases were not abnormal.Of the 7 children with epilepsy,6（85.71%）had general seizures and 1（14.29%）had focal seizures.7.In the CNSC group,white blood cells in 5 children was more than 100×10⁹/L（141.71-763.49×10⁹/L）,including 1 case of cerebellar infarction and cerebral atrophy,2 cases of intracranial hemorrhage,1 case of CNSL,1 case of CNSL,cerebral infarction and intracranial hemorrhage.8.There was no statistical difference between the CNSC group and the control group for complete remission of bone marrow morphology at the end of induction remission chemotherapy;Excluding APL,the comparison between the two groups for≥10^-2 bone marrow MRD at the end of induction remission chemotherapy showed that the occurrence of CNSC was a risk factor for≥10^-2 MRD at the end of induction remission chemotherapy.Conclusion1.Leukocyte count,risk classification and age are associated with the development of CNSC,with high risk group and age≤6 years being independent risk factors for the development of CNSC in children with AL.2.Adverse genetic characteristics increase the risk of AL（except APL）complicated with CNSC.3.CNSC can affect the MRD level at the end of induction remission chemotherapy treatment in children with AL（except APL）.4.CNSC is most likely to occur after 7 days of chemotherapy,and hyperleukocytic acute leukemia is prone to a variety of central nervous system complications..5.The most common clinical manifestations in CNSC are seizures,headache,nausea and vomiting,and the most common diseases are cerebrovascular disease,CNSL,intracranial infection,and epilepsy.