Clinical Significance Of Dynamic Monitoring The Minimal Residual Disease Of The Cerebrospinal Fluid In Children With Central Nervous System Leukemia

With the development of diagnosis and treatment in children with acute lymphoblastic leukemia(ALL), disease free survival has been greatly improved. ALL has become a curable disease. However, leukemia is a heterogeneous disease, using the same treatment, treatment outcome is different. Part of children with strong chemotherapy and can not produce the desired therapeutic effect, and the other part of children, it does not require very strong chemotherapy.Because of the blood-cerebrospinal fluid barrier existed,the chemotherapeutics can not reach the level of the therapy in central nervous system, then it becomes the best shelter of the leukemic cell.and the central nervous system leukemia (CNSL) relapse is one of the major cause of relapse of the leukemia.Whether CNSLwith new diagnosised or not is one of the independent factor of the risk of acute lymphoblastic leukemia(ALL).it has important significance to institute the eligible treatment and judgment of the prognosis. Because of the various kinds reason, the traditional cerebrospinal fluid (CSF) morphology can not be contented to diagnosis of the CNSL, so it is the criticality to explore the more sensitive examination of cerebrospinal fluid for the early diagnosis in CNSL.Our study used the monoclonal antibody direct immunofluorescence to detect the clinical significance of minimal residual disease in CSF, to compare the morphology of the CSF at the same time, and to search which approach is more sensitive. To enhance cure rate and long-term disease-free survival rate and to improve the quality of life for patients, we compared the treatment between low and middle risk group and high risk group patients when the CNSL relapsed, in order to find the most appropriate chemotherapy, and to avoid over-treatment and inadequate treatment, to make sure using individual treatment.Objectiveâ‘ Examine the morphology and MRD of the cerebrospinal fluid at the same time ,and compare the sensitivity of these two approaches, to find which approach strongly indicates the occurrence of the CNSL when the two results are inconsistent.â‘¡to know the clinical significance of CSF at different stages for the development of CNSL.â‘¢To search the most appropriate chemotherapy in children with CNSL who was in high risk group or in middle and low risk group, we compared the treatment of prophylaxis and therapy for CNSL in order to individual therapy.Methodsâ‘ Using monoclonal antibody directed immunity and multiparameter flow cytometry to detect the CSF MRD at new diagnosised,remission induction and at different periods of the remission induction respectivelyâ‘¡Use the slide centrifugation and rui-Giemsa staining to examine the morphology of cerebrospinal fluidâ‘¢We examine the morphology and MRD of CSF of 85 cases in children with ALL at different stages of complete remission by FCM,and analysis the MRD of CSF in prevention and treatment significance in CNSL.Resultsâ‘ There was 16 patients had CNSL happened in our study,7 of them were at new diagnosed time,and the other 9 were relasped in complete remission,their morphology and MRD of CSF were all positive at that time.â‘¡It was significant difference in children with ALL that relative risk of CNSL happened was 3.46-fold in early stage of complete remission and 9-fold in mid-advanced stage of complete remission whose MRD of cerebrospinal fluid was positive persistent or from positive to negative at the same period.â‘¢We compared 2 groups between the strength triple intrathecal and routine triple intrathecal in children whose morphology of CSF was negative but MRD was positive at different stages of complete remission. The CNSL relapse rate of the forward group was obviously lower than the afterward group .â‘£the relapse rate of CNSL was higher in complete remission for these children of high risk group only using triple intrathecal and strength chemotherapy at new diagnosed , the re-relapse rate of CNSL was lower for using triple intrathecal and strength chemotherapy and CRT in different CR stage ;but it was good effect that using triple intrathecal and strength chemotherapy for these children who was in low-middle risk group.Conclusionâ‘ Central nervous system leukemia was one of the main causes of treatment failure in children with ALL, morphology of CSF was the diagnosis gold standard of CNSL.It was show that when the morphology of CSF and MRD was inconsistent,especially when the morphology of CSF was negative but the CNSL was highly suspected in clinical, the immunology was more predicted the CNSL happened ,it was more necessary to examine the MRD of CSF that it could provide important evidence for the clinical diagnosis and treatment of CNSL.â‘¡MRD positive changes at any time in complete remission may indicate recurrence of CNSL ,so we need to adjust therapy by MRD in CSF,and to strength the treatment of CNSL as soon as possible. It was show in our data that the relative risk of CNSL happened was higher manifest of the MRD was positive persistent or negative transfer in positive than the MRD was persistent negative patients at medium-term and in late stage of CR.â‘¢Although we could not diagnosis the CNSL for these people whose MRD of CSF were positive but morphology of CSF were negative at CR stage ,but it need strengthen the treatment of intrathecal injection in clinical. It was clear that strengthen the treatment of intrathecal injection for CNSL therapy was effect significance and it could more better to prevent and reduce the CNSL relapses.â‘£When the CNSL relapsed in CR for low and medium risk group patients,the effect was strong significant for the IT with strength chemotherapy,and the re-relapse rate was very low,but it was need CRT to decrese re-relapes of CNSL for high risk patients. For the HR-ALL patients who were relapsed in CR also need CRT after the IT with strength chemotherapy.