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Investigation of Clinial Death Associated Factors and Experimental Study in Children with Acute Leukemia

Author: SunYan
Tutor: HuQun
School: Huazhong University of Science and Technology
Course: Pediatrics
Keywords: Leukemia Acute Analysis on death Child Notch 1 B-lineage Immunohistochemistry RT-PCR
CLC: R733.7
Type: Master's thesis
Year: 2011
Downloads: 14
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Abstract


Objective: To evaluate children with acute leukemia (AL) in the hospital cause of death, time of death and its related factors. Methods: A retrospective analysis of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology 2000-2009 nearly 10 years, 64 patients were treated in hospital death the AL cases of information. Results: Time of death: the time from diagnosis to death one day to 50 months, 34 cases diagnosed in January of death (early death) (53.1%), 18 patients died within 1 to 6 months (28.1 %); 12 cases> 6 months (18.8%) deaths, including childhood ALL patients relapse death withdrawal five years. AL chemotherapy program points, 64 deaths in children in the early death of 34 patients (53.1%), including 11 cases of death before chemotherapy, remission induction phase of 23 cases; maintenance therapy in 11 patients (17.2%); nine cases of early intensive treatment (14.1%); difference was statistically significant compared to consolidation therapy in 6 patients (9.4%); prevention and treatment of extramedullary 3 cases (4.7%) 1 (1.6%); relapse after discontinuation of death; remission induction stage and the remaining stages (P lt; 0.05), accounting for the time of death of the first, followed by chemotherapy and maintenance treatment phase before. Cause of death: 64 deaths in children, infection-related deaths in 45 patients (70.3%) including respiratory infections in 25 patients (55.6%), gastrointestinal infections and sepsis 4 cases, skin infection in 2 patients, urinary tract infection and otitis media cases; died from the disease itself recurrence in 29 cases (45.3%), marrow relapse 14 cases, 15 cases of extramedullary relapse, including intracranial invasion or recurrence of 11 cases of lung and testicular relapse 2; bleeding-related death 26 patients (40.6%), 2 cases of intracranial hemorrhage in 16 cases, DIC 7 cases of pulmonary hemorrhage, gastrointestinal bleeding patients; died of chemotherapy-related side effects, including pancreatitis, renal failure in 1 case. Analysis showed that infection accounted for the first cause of death (P lt; 0.05). 3 at diagnosis and death-related factors: 1) Age: 64 deaths in children aged 0 to 1 5 cases, 1 ~ 10y 38 patients ≥ 10y 21 cases. Infants and adolescents group, 1 ~ 10y group comparison was statistically significant (P lt; 0.05); 2) gender composition: 48 males and 16 females, boys higher (P lt; 0.05); 3) peripheral blood WBC count: WBC count 50 ~ 100 × 109 in 9 patients (9/58, 15.5%), and ≥ 100 × 109 11 cases (11/58, 19.1%), a high white blood children and I, there are significant difference (P lt; 0.05); 4) LDH levels grouping: of LDH ≥ 300U / L in 26 cases, lt; Comparison of 300U / L 8 Li, with the normal group, the difference without significantly with sex (P> 0.05); 5) risk points layer: low-risk children in 7 cases, in crisis 13 cases, 36 cases of high-risk groups, children with high-risk group was statistically compared to the other groups (P lt; 0.05); 6) whether the organ infiltration: death group first visit 45 infants organ infiltration, and 19 cases of non-organ infiltration, a significant difference (P lt; 0.05) with no organ infiltration. 4. Factors of early death: 1) Age: 64 deaths of children, 5 infants died of early death stage (P lt; 0.05); 2) Gender: 24 males and 10 females, no significant difference ( P gt; 0.05); 3) peripheral WBC count: 11 cases WBC ≥ 100 × 109 / L in children, nine cases of early death, and the difference was statistically significant (P lt; 0.05); 4) LDH level: LDH ≥ 300U / L in children 16 cases, only 1 case of the LDH at normal levels (P lt; 0.05); 5) risk stratification: high-risk 20 cases, five cases risk, low-risk group 3 cases Uncategorized six cases. Children with high-risk group vary significantly (P lt; 0.05); 6) newly diagnosed with or without tissue invasion: newly diagnosed children with 15 cases of infiltration, non-infiltration children with 19 cases, statistical analysis shows no significant difference (P gt; 0.05); ) whether M3: 5 cases of M3 children early death, 3 patients died of intracranial hemorrhage and DIC patients died of infection, 1 died of intracranial extensive infiltration statistically significant (P lt; 0.05). Conclusion: 1.AL children deaths occurred mainly in the remission induction period. Followed prior to chemotherapy and maintenance treatment phase. 2 cause of death, infection topped the list, followed by disease recurrence, hemorrhage, drug toxicity. 3. Newly diagnosed boys, babies, children at high risk, high white blood cell hyperlipidemia, organ infiltration AL death related. 4. Newly diagnosed infants, high leukocyte hyperlipidemia, high-risk children, high LDH levels, M3 children with AL early death related. Purpose: a growing number of studies suggest that the Notch signaling pathway in tumorigenesis, acute lymphoblastic leukemia (ALL) is the most common childhood leukemia, among which the most common B-lineage. This paper aims to study the Notch1 in the relationship between the expression of B-ALL in children and children with newly diagnosed clinical data, response to chemotherapy and post-efficacy, to explore the role of Notch1 in B-ALL in children for the treatment and prognosis of leukemia provide reasonable suggestions. Methods: 1. SABC immunohistochemical method to detect my first visit, 49 cases of children with B-ALL and 20 cases of non-malignant blood disease bone marrow cells Notch1 protein expression levels; 2 RT-PCR method to determine the Notch 1 gene in children with acute leukemia ( AL) of the expression. : 1.Notch1 protein expression mainly in the cytoplasm, a few in the nucleus. Admitted since January 2007 to 2010 and data integrity AL 74 cases in children with B-ALL 49 cases (66.2%), the positive expression in 15 cases (30.6%); 13 cases of T-ALL (17.6%), 10 were positive (76.9%); acute myeloid leukemia (AML), 12 patients (18.1%), 8 were positive (75%); in the control group of 20 patients with non-hematologic malignancies in children with bone marrow smears were positive in Expression (15%). B-ALL, T-ALL, AML with the control group compared to the differences were significant sex (X2 = 6.64, X2 = 12.654, X2 = 8.875, P lt; 0.05); B-ALL group compared with T-ALL group significant difference (X2 = 10.438, P lt; 0.05); B-ALL and AML are different (X2 = 6.206, P lt; 0.05); compared to T-ALL and AML group no statistically significant difference (X2 = 0.326, P gt; 0.05); abnormal expression of Notch1 protein in B-ALL the differences meaningful comparison with the control group (P lt; 0.05), but significantly lower than the T-ALL and AML (P lt; 0.05). 2 of Notch 1 protein expression with children with newly diagnosed B-ALL factors 1) Age 49 cases of children with B-ALL, 15 cases of Notch 1-positive the Notch 1 negative in 34 cases, aged between 1 ~ 14y, which 0 ~ 1y group Notch 1 positive group 1 cases, Notch 1 negative group 0 cases; the 10y group of Notch 1 positive group 13 cases, Notch 1 negative group 27 cases, ≥ 10y group Notch 1-positive group 1 patients, Notch 1 negative group 7 cases. Each age group and between-group differences were not statistically significant (P gt; 0.05). 2) gender Notch 1-positive group, 12 males and 3 females, Notch-negative group of 21 male and 13 female patients, no statistically significant (X2 = 1.66, P gt; 0.05); 3) peripheral WBC of Notch 1 the WBC lt; positive group of newly diagnosed peripheral blood of 50 × 109 cases, 50 × 109 ~ 100 × 109 2 patients ≥ 100 × 109 cases; the WBC lt of Notch-negative group of newly diagnosed peripheral blood; 50 109 13 cases, 50 × 109 ~ 100 × 109 2, ≥ 100 × 109 2 cases between the two groups were not statistically different (X2 = 1.832, X2 = 1.667, X2 = 0.925, P gt; 0.05); 4) MICM typing ① FAB parting Notch 1 positive group L1 4 cases, L2 9 cases, not parting (lymphoma and ALL) cases; L1 8 cases of Notch negative group, L2 25 cases of unclassified (lymphoma and ALL) 1 cases. No statistically significant difference (X2 = 2.512, P gt; 0.05); ② B Department subtyping Notch positive group mature B3 cases, ordinary B 12 cases of Notch 1 negative group mature B 3 cases, the ordinary B lineage 31 cases no significant difference (P gt; 0.05); (3) chromosome karyotype Notch 1 positive group, normal karyotype 11 cases of 45, XY, -7 1, Ph chromosome 1 cases; of Notch 1 negative group of normal karyotype 24 cases , Ph chromosome 1, Ph chromosome,, and -7 chromosome 1 cases, patients 47, XY, 12p-, mar. (X2 = 1.891, P gt; 0.05); ④ fusion gene Notch 1 positive group of 13 patients normal, one cases TEL/AML1; of Notch negative group, 24 patients were normal, three cases TEL/AML1, 2 cases of BCR / ABL, 1 case of TLS / ERG (X2 = 1.329, P gt; 0.05); 5) clinical risk Notch 1 positive group, 5 cases of low-risk group, risk group in four cases, six cases of the high-risk group; Notch 1 negative group 14 cases of the low-risk group, risk group in the 11 cases, nine cases of the high-risk group. Differences between groups were meaningless (X2 = 1.832, X2 = 0.719, X2 = 0.855, P gt; 0.05); 6) early response to treatment Notch 1 positive group, the sensitive 10 cases of prednisone induction test is not sensitive to one cases, d19 days 11 cases of bone marrow suppression, no suppression d33 complete remission (CR) 13 cases, did not ease the two cases; of Notch 1 negative group prednisone induction test is sensitive to all the 23 cases of children with sensitive d19 days 26 cases of bone marrow suppression, not inhibition of the two cases, CR29, not ease the two cases. The difference between the two groups were not statistically different (X2 = 2.321, X2 = 0.685, X2 = 0.603, P gt; 0.05). 3 of Notch 1 protein expression in children with late efficacy (followed up for more than 6 months) the relationship of the efficacy of the children were followed up for more than six months for statistical effect of Notch-positive group 7 cases, poor results Group 6 cases (5 cases of recurrence, poor to give up one cases); effect of Notch negative group 22 cases, the effect is poor in 4 cases (4 cases are recurrence). The comparison shows the difference was significant (X2 = 4.331, P lt; 0.05) Conclusion: 1.Notch 1 protein in B-ALL high expression, but lower than the expression of T-ALL and AML. 2.Notch 1 protein expression in newly diagnosed children age, gender, WBC count, MICM genotyping, clinical risk and early response to treatment is no significant correlation. 3.Notch1 high expression may be related factors of post-treatment in children with poor prognosis in B-ALL.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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