The Influence Of Treatment Delay Oil The Relapse Of Children With B-cell Acute Lymphoblastic Leukemia

Objectives:The overall survival of children with acute lymphoblastic leukemia,especially B cell acute lymphoblastic leukemia,has tremendously improved in the past 50 years.With the continuous optimization of chemotherapy regimens,treatment-related mortality has fallen below 5%.Relapse at different stages of the disease has been a major factor limiting the success of treatment in children with B-ALL.Therefore,finding the factors that cause relapse becomes a key point for improving the prognosis of B-ALL.Chemotherapy is the traditional treatment of B-ALL.Different chemotherapy intensity,differences in pharmacokinetics of individual,and so on,may cause the child to delay the treatment due to various reasons.Whether the delay of treatment is closely related to relapse is still a hot topic.In this study we analyzed the clinical information of children with acute lymphoblastic leukemia treated with CCLG-ALL-2008 in our single center,and explored whether treatment delay is a factor affecting the relapse of children with B-ALL and what causes delay in the treatment to improve the prognosis.Patients and methods:This was a retrospective analysis in which 412 children with B-cell ALL was analyzed and treated by CCLG-ALL-2008 from January 2011 to December 2014.Children who met the following criteria were enrolled in the study:completed induced remission therapy,early intensive treatment,consolidation therapy,delayed intensive therapy,and the children were excluded if they showed primary drug resistance(minimal residual disease,MRD?10-2),persistent non-remission and relapse of disease or gave up treatment due to any other reasons in the four phases of treatment course.Two hundred and eight-seven children were chosen out of 412 patients for this study and 222 children were classified into the group with treatment delay.The relationship between treatment delay and relapse was compared in the thesis.Two hundred and twenty-two patients with different treatment delay time were divided into different groups,and the relationship between treatment delay time and relapse was compared.The reasons for treatment delay which may lead to relapse easily were analyzed in this thesis.This study used SPSS 23.0 to analyze the data by Chi-square test,COX proportional risk regression model,Kaplan-Meier Curve Survival Analysis,Bilateral Log-Rank test,Life table method.The follow-up visit was December 1st,2018.p<0.05 was considered to be statistically significant.Results:Comparison with non-delay group,222 patients had a delay in treatment which accounted for 77.35%(222/287).Seven years RFS in treatment delay group was 89%±3%and 98%±2%in non-delay group which reached a statistical difference(p<0.05).The relapse rate was higher in the delayed group which reached a statistical difference compared with the non-delayed group.(p<0.05).According to the 25%(15 days),50%(32 days),and 75%(76 days)delays of the treatment,the treatment delay time was divided into 4 groups.There is a significant difference between relapse group and non-relapse group when the treatment delays more than 76 days compared with less than 15 days(p<0.05).There is no significant difference between relapse group and non-relapse group when the treatment delays more than 15 days and less than 32 days compared with treatment delay less than 15 days(p>0.05).There is no significant difference between relapse group and non-relapse group when the treatment delays more than 32 days and less than 76 days compared with less than 15 days(p>0.05).There is no significant difference between relapse group and non-relapse group when the treatment delays more than 32 days compared with less than 32 days(p>0.05).The COX regression modal was used to analyze the risk factors influencing relapse rate among 287 children.The effect of treatment delay week on relapse rate was statistically significant(p<0.05),especially more than four weeks is an independent prognostic factor influencing relapse.MRD in treatment for 12 weeks was an independent prognostic factor influencing relapse(p<0.05).The age,gender,the white blood cell count at first diagnose,fusion gene,prednisone response,blast cells on treatment for 15 days(D15)and 33 days(D33)have no statistically significant on relapse rate(p>0.05).The COX regression modal was used to analyze the risk factors influencing relapse rate among 222 children with treatment delay.The effect of MRD detecting on treatment for 12 weeks on relapse rate was statically significant(p<0.05).The white blood cell count at first diagnose showed a tendency in affecting relapse rate(p=0.061).Others factors such as the age at first diagnose,gender,fusion gene,prednisone response,blast cells on D15 and D33,and treatment delay time groups(treatment delay time group:1.<15 days;2.?32 days)had no statically effect on relapse rate(p>0.05).The COX regression modal was used to analyze the risk factors influencing relapse rate among 222 children with treatment delay.The effect of fusion gene and treatment delay time group(treatment delay time group:1.<15 days;2.?15 days and<32 days;3.?32 days and<76 days;4.?76 days)on relapse rate had a tendency to statistic differences(p=0.062,p=0.064).The age at first diagnose,gender,the white blood cell count at first diagnose,prednisone response,blast cells on D15,D33 and 12 week had no statically effect on relapse rate(p>0.05).The COX regression modal was used to analyze the risk factors causing treatment delay which influenced relapse rate.Simple Myelosuppression was an independent prognostic factor influencing relapse(p<0.05).Other factors such as sepsis,pulmonary infection,liver damaged by drugs,severe mucositis(oral,perianal,intestinal and urinary tract infections),infectious diseases,two complications,and three complications didn't reach statistically significance on relapse rate(p>0.05).Conclusion:(1)Treatment delaying more than four weeks was an independent prognostic factor influencing relapse.MRD on treatment for 12 weeks was an independent prognostic factor influencing relapse.(2)The treatment delay due to the suppression of bone marrow was an independent prognostic factor influencing relapse.