Researches On Stratified Diagnosis And Treatment-related Factors In Childhood Acute Lymphoblastic Leukemia

With the development of diagnosis and treatment in children with acute lymphoblastic leukemia(ALL), disesse 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. Hence it is needed to differentiate children with different risk classification, and diagnosis and treatment of a stratified. Both strengthen the efficacy, but will also reduce the excessively strong chemotherapy in patients with part of the second tumor and the risk of long-term decline in the quality of life.Objective (1) To find the fusion gene testing conditions, and establish a stable detection methods, improve the diagnosis of type MICM. (2) According to the risk factors, we set a division of children with different treatment, evaluated treatment outcome of each group. ( 3) To establish the bone marrow MRD detection method. (4) Observation the relationship of the early response to treatment and bone marrow MRD levels and prognosis.Methods (1) Use nested RT-PCR method,to separate the single nuclear cell from bone marrow specimens , extracting RNA, and RT-PCR, gel electrophoresis, then under UV to record specific bands by camera. (2) According to various risk indicators to determine risk stratified, hierarchical chemotherapy. (3) Using flow cytometry, the combined monoclonal antibodies to tag cells and found that abnormal cell phenotype. (4) Analysis of early treatment response and bone marrow MRD level, and the relationship to relapse.Results (1) Establish the nested RT-PCR method to detect gene fusion of leukemia patients, the sensitivity is up to about 10-5, results are stable and reliable, and the result can use to provide a reliable basis for stratified diagnosis and treatment. (2) BCR-ABL-positive ALL children have poor prognosis, TEL-AML1 positive response to good treatment. (3) Prednisone poor response, 19 days for bone marrow as M2/M3 patients relapse rate was significantly higher than that have a good response and bone marrow for patients with M1 Group. (4) MRD level of bone marrow after induced-therapy, > 1% Group have high relapse rate than <1% group.Conclusion (1) Successfully established nested-PCR method in detecting the fusion gene of children with acute lymphoblastic leukemia. The method is rapid, sensitive, simple, economic, reliable, and treatment for clinical layered to provide a reliable basis. (2)According to the preliminary clinical data of BCR-ABL-positive ALL children tend to relapse, TEL-AML1 positive ALL children with a better response. (3) Early treatment of adverse reactions associated with the relapse significantly. (4) MRD level of bone marrow after induced-therapy associated with the relapse rate.