A Study On The Effect And Side-effect Of Therapy With Intermindiat-dose Cytarabine In Childhood Acute Lymphoblastic Leukemia

Objective: To explore the difference of the survival condition of the patients between the groups with and without intermediate dose cytarabine and the 5-event free survival (5-EFS)of them;To explore the prognostic factors that affect the long term survival of the patients;To observe the side-effect in the cases which use intermediate dose cytarabine;To investigate the difference of concentrations of cytarabine in cerebrospinal fluid between the groups using intermediate dose cytarabine and standard dose cytarabine and the relationship between concentrations of cytarabine in cerebrospinal fluid and the side-effect in central nervous system,and to judge the value of using intermediate dose cytarabine to treat children patients with acute lymphoblastic leukemia.Methods: 1. Survival analysis and cox-proportion model(cox modle):The cases who initially diagnosed from January ,2002 to January,2005 in our department were carried out the survival study with retrospective cohort method,design the case history table,extract the information of age,sex,the number of WBC,therapy methed and time etc,and followed up the cases by telephone and letter,added up the survival time.The patients who were previously diagnosed from January,2005 to January, 2008 in our department are treated in the same way.Statistical analysis: survival analysis use Kaplan-Meier way, the comparison between survival curves using Log-Rank test.Meanwhile,cox modle is used to explore the prognostic factors of the acute lymphoblastic leukemia cases of long outcome,both using the single-factor and multiple-factors analysis.The same with the cases who were previously diagnosed from June ,2002 to June ,2007 in our department, calculate the 5-EFS.2. Observation of side effects:To observe the side effect of the acute lymphoblastic leukemia cases with intermediate dose cytarabine between May,2006 and January, 2008, observe the side effects on respiratory system,recirculating system,alimentary system,etc; and to deal with them, take notes.3. Determination of drug concernrtation:Samples are collected from the patients with acute lymphoblastic leukemia who received intermediate dose cytarabine and also from the patients who used standard dose cytarabine as control. Then the drug concentration with HPLC method is determined, comparing the two groups. The data are divided into two groups according to whether there is side effect on central nervous system. Then compare the drug concentration between the two groups.Results: There is a difference to the total survival time between the two groups with and without intermediate dose cytarabine.In the group without moderate dose of cytosine arabinoside, there was no difference between male and female. The 5-EFS of the patients with acute lymphoblastic leukemia in our department is 55.3%.Through cox model,we found that, in the single-factor analysis of the group without intermediate dose cytarabine,the prognostic factors of the acute lymphoblastic leukemia is morphologic classification,and in the multiple-factor analysis,the factors are age,morphologic classification and the number of juvenile peripheral blood cells.In the group with intermediate dose cytarabine the survival time was different between male and female.In cox model,the single-factor analysis tells us that the prognostic factors of the acute lymphoblastic leukemia cases of long outcome is sex, and in the multiple-factor analysis,the factors are sex and the number of juvenile marrow cells.In cox model for all the cases in five years,the single-factor analysis tells us that the prognostic factors of the acute lymphoblastic leukemia cases are morphologic classification and sex, in the multiple-factor analysis,the factor is sex. Except that 3 cases caught severe infection,there were no other lethal side effects.Through determination of drug concentration , we found that,the concentrations of cytarabine in cerebrospinal fluid between the group that uses intermediate dose cytarabine and the group that uses standard dose cytarabine were different.The concentrations of cytarabine in cerebrospinal fluid between the group with side effect on central nervous system and group without side effect on central nervous system were hardly different.Conclusion: 1. The use of intermediate dose cytarabine can increase the survival time of the patients with acute lymphoblastic leukemia,and the the surviva time of the female is longer than the male.2. In the group without intermediate dose cytarabine,the prognostic factors are age,morphologic classification and the number of juvenile peripheral blood cells,and in the group with moderate dose of cytarabine,the prognostic factors are sex and the number of juvenile marrow cells.It changes the prognostic factors.3. The side effect of intermediate dose cytarabine is acceptable,we don't find lethal side effects.4. Moderate dose of cytarabine can penetrate the blood-brain barrier.