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Investigation Of Clinial Death Associated Factors And Experimental Study In Children With Acute Leukemia

Posted on:2012-03-20Degree:MasterType:Thesis
Country:ChinaCandidate:Y SunFull Text:PDF
GTID:2214330362957361Subject:Academy of Pediatrics
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Objective:To explore the dead reasons, dead time and related factors of acute leukemia in children .Methods:The clinical information of 64 dead cases with AL who were admitted to Huazhong University of Science of Tongji Hospital, Tongji Medical College between 2000-2009 were Retrospectively analyzed.Results:1.The time of death: the time from diagnosis to death was 1 day to 50 months, 34 cases died in 1 month (early death) (53.1%), 18 cases died within 6 months(28.1%); 12 cases> 6 months later(18.8%), 1 case of ALL boy died of relapse with drug withdrawal 5 years. Chemotherapy program to points according to AL, 64 cases of death, early death in children with 34 patients (53.1%), including chemotherapy before 11 cases, induced ease stage 23 cases; Maintenance treatment in 11 patients (17.2%); Early intensive treatment 9 cases (14.1%); Consolidate treatment in 6 cases (9.4%); Central nerve system prevention and treatment of 3 patients (4.7%); After drug withdrawl of 1 case (1.6%); Induction ease stages and the rest of the phase difference in a statistically significant (P < 0.05), accounting for the first time of death,followed by chemotherapy before and maintenance treatment phase.2.The death reasons: 64 cases of children with infection-related deaths in 45 case(70.3%), of which 25 cases of respiratory tract infection(55.6%), each 4 cases of gastrointestinal infection and septicemia , 2 cases of skin infections, urinary tract infection 1 cases, 1 case of otitis media; recurrence related death in 29 cases, of which 14 cases of bone marrow relapse, marrow foreign recurrence in 15 cases, 11 cases of intracranial infiltration or recurrence, lung and testicular recurrence in 2 cases separately; bleeding-related deaths in 26 cases, of which 16 cases of intracranial hemorrhage, 7 cases of DIC, 2 cases of pulmonary hemorrhage, 1 case of gastrointestinal bleeding; chemotherapy-related side effects in 2 cases, of which pancreatitis, renal failure in 1 case separately.Analyzed show infection was the first place among the death reasons(P<0.05).3. Death factors:1) Age: 64 deaths in children, 0 ~ 1y in 5 cases, 38 cases ,≥10y 21 cases, compared with 1 ~ 10y group,≥10y group , 0 ~ 1y groups had a statistically significant (P < 0.05).2) Gender constitute: boys of 48 cases and girls of 16 cases, (P < 0.05), the boy is higher;3) Peripheral WBC count: The WBC count those 50 to 100 x 109 9 cases (9/58,15.5%),≥100 x 109 11patients(11/58,19.1%); the highest group there is significant difference (P < 0.05). 4) LDH level: LDH≥300U/L 26 cases, compared with normal children (P﹥0.05);5) Risk stratification: low risk 7 cases, middle risk of 13 cases,high risk of 36 cases,high-risk group compared to the rest of the group of children (P < 0.05).6) Organ infiltrating: death group of patients have 45 first organ infiltrates, and statistically significant (P < 0.05).4. Early death related factors : 1) Age: 64 cases of death, 5 cases of infants were all died in early death infant stage (P < 0.05). 2) Gender: boys of 24 cases, girls of 10 cases (P > 0.05). 3) Peripheral WBC count: 9 cases of WBC 100 x 109 / L children early death among 11 cases (P < 0.05). 4) LDH level: LDH≥300U/L were 16 cases , only 1 case in the normal level (P < 0.05). 5) Risk stratification: high-risk 20 cases,middle risk in 5 cases, low-risk group 3 cases, 6 cases without classification. High-risk group of children difference significantly (P < 0.05). 6) Organ infiltration: when newly diagnosed 15 cases of organ infiltration, 19 cases without (P > 0.05). 7) Whether M 3: 5 cases of M 3 were all early death (P < 0.05).Conclusion:1. The death of AL in children occurs mainly in remission induction.2.Causes of death accounted for the infection first, followed by disease recurrence, bleeding, drug toxicity.3. Boys, infants, children at high risk, high white blood cell anemia, organ infiltration when first diagnosed have relation with AL death. 4. Infants, high white blood cell anemia, high-risk children, high LDH levels have relation with AL early death. Objective:More and more studies suggested that Notch signaling pathway correlated with the occurrence of cancer, Acute lymphoblastic leukemia (ALL) is the most common childhood leukemia,and B-ALL was the most common of ALL, This paper aims to study the relations between the Notch 1 expression in B-ALL and their clinical data ,early effect of chemotherapy and late prognose.Methods:1. SABC immunohistochemistry was used to detect Notch1 protein expression of bone marrow cells of 49 patients newly diagnosed B-ALL patients in our hospital and 20 non-malignant blood diseases. 2. RT-PCR was used to detect he gene expression of Notch 1 in AL of children.Results:1. Notch 1 protein expression mainly in the cytoplasm,less in nucleus. Since January 2007 ~ March 2010 and material complete were 74 cases of AL children, including B-ALL49 cases (66.2%), positive express 15 cases (30.6%); T - ALL13 cases (17.6%), 10 cases positive express (76.9%); Acute myeloid leukemia (AML) 12 cases (18.1%), 8 cases of positive express (75%); The control group 20 cases of children non-malignant bone marrow, positive expression in 3 cases (15%). B - ALL, T - ALL, AML, as compared with control group was significant difference (X2 = 6.64, X2 = 12.654, X2 = 8.875, P < 0.05). B - ALL group group compared with T - ALL significant difference (X2 = 10.438, P < 0.05). B - ALL compared with AML have difference (X2 =6.206, P < 0.05). T - ALL group compared with AML group was not statistically significant (X2 = 0.326, P > 0.05); Notch 1 protein in B - ALL was abnormal expression, compared with controls difference have meaning (P < 0.05), but obviously lower than T - ALL and acute myelogenous leukemia (P < 0.05).2. Notch 1 protein expression in B - ALL relationed factors when newly diagnosed1) Age 49 cases B - ALL in children with Notch1 positive 15 cases Notch1 negative34 patients ,aged 1 ~ 14y ;0 ~1y group there was Notch1 positive 1 case, Notch 1 negative 0 case; group 1 ~ 10y Notch1 positive 13 cases, Notch1 negative 27 cases,≥10y group, Notch 1 positive 1 case, of Notch 1 negative 7 cases. Every age group compared non difference (P > 0.05).2) Gender Notch 1 positive group of male in 12 cases, female 3 cases, Notch 1 negative group of male 21 cases, female 13 cases (X2 =1.66 ,P > 0.05);3) Peripheral WBC Notch 1 positive group peripheral WBC begin with peripheral WBC < 50 x 109 4 cases, 50 x 109 ~ 100 x 109 2 cases, 1 case with 100 x 109; Notch 1 negative group of peripheral blood WBC < 50 x 109 13 cases, 50 x 109 ~ 100 x 109 2 cases, 100 x 109 in 2 cases, compared between the two groups were no statistically significant (X2 = 183.2, X2 = 1.667, X2 = 0.925, P > 0.05);4) MICM classification①FAB Notch 1 positive group L1 4 cases, L2 in 9 cases, not classification(lymphoma and ALL) in 2 cases; Notch 1 negative group of L1 8 cases, L2 25 cases, not classification (lymphoma and ALL) in 1 case. (X2 = 2.512, P > 0.05) ;②The sub-type of B Notch 1 positive group of mature B 3 cases, ordinary B in 12 cases, Notch 1 negative group of mature B in 3 cases, ordinary B in 31 patients ,(P > 0.05);③Chromosomal karyotype Notch 1 positive group normal karyotype 11 cases, 45, XY, - 7 in 1 case, Ph chromosomes in 1 case; Notch 1 negative group of normal karyotype 24 cases, Ph + chromosomes 1 case, Ph + chromosome and -7 chromosome in 1 case, and 47, XY, 12p -, mar + in 1 case (X2 = 1.891, P > 0.05);④Gene fusion Notch 1 positive group, of 13 patients with normal, 1 case with AML1; Notch 1 negative group of 24 patients normal, 3 cases TEL / AML1, 2 cases of BCR/ABL, 1 case of TLS/ERG. /. (X2 = 1.329, P > 0.05); 5) Clinical risk Notch 1 positive group low-risk group in 5 patients, middle risk category 4 cases, high-risk group of 6 cases; Notch 1 negative group low-risk group of 14 cases, 11 cases in the intermediate risk, high-risk group 9 cases. Each group differences meaningless (X2 = 183.2, X2 = 0.719, X2 = 0.855, P > 0.05);6) Early treatment response Notch 1 positive group prednisone, 10 cases were induced test sensitive, not sensitive 1 case, d19 days bone marrow there were 11 cases inhibited, non-inhibited in 2 cases;d33 days complete remission 13 cases (CR), 2 cases not ease; Notch 1 negative group of prednisone induction test sensitive 23 cases were all sensitive, d19 days bone marrow 26 patients inhibited, non-inhibited in 2 cases, CR29 cases, not ease in 2 cases. Two groups of comparisons were no statistically significant differences (X2 = 2.321, X2 = 0.685, X2 = 0.603, P > 0.05). 3. Notch1 protein expression with the later curative effect (follow-up children more than 6 months) To cross over 6 months above the curative effect of children ,Notch 1 positive group statistical, good effect in 7 cases, poor effect group 6 patients (recurrence up in 5 cases, poor effect 1 case); Notch 1 negative group effect is good 22 cases, poor effect in 4 (4 cases for recurrence) (X2 = 4.331, P < 0.05)Conclusion:1. Notch1 protein in the abnormal expression of B-ALL, but lower than T-ALL and AML.2. Notch 1 expression in children newly diagnosed has little to do with age, sex, WBC count, MICM classification, clinical risk and early treatment response.3. Notch1 protein expression may be associated with poor prognosis factors. in later effacy of B-ALL。...
Keywords/Search Tags:leukemia, acute, cause of death analysis, children, Notch 1, B-lineaged, immnohistochemistry, RT-PCR
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