Systematic Review Of Prognostic Factors In Children And Adolescents With Anaplastic Large Cell Lymphoma

PurposeSystematical review method was applied for prognostic factors of anaplastic large cell lymphoma(ALCL)in children and adolecents,including age,St.Jude staging,morphologic and phenotypic features,whether there are group B symptoms,whether there are extranodal extension,involving mediastinal,skin,and bone marrow.whether serum LDH level elevates,Whether MDD is positive in bone marrow or peripheral blood,and whether there is high titer antibody against ALK gene in vivo,in order to accuratly evaluate the impact of these factors on survival of children and adolescents with anaplastic large cell lymphoma.MethodWe searched medical databases including CNKI,Wan Fang,VIP,Pubmed,EMBase,the Cochrane Library,and prognostic datas of anaplastic large cell lymphoma in children and adolecents were collected from clinical retrospective cohort analysis of correlation.The retrieval time was between databases established to Dec.31,2019.After that,two reviewers independently screened the literature,extracted datas and evaluated the quality of the researches,the extracted data were statistically analyzed using the Review Manager 5.3 software.Risk ratio(HR)and95% confidence interval(95% CI)were used for evaluation to determine the influence of each factor on Overall survival(OS)or event-free survival(EFS).Meanwhile,the literature was reviewed.ResultsA total of 13 retrospective cohort studies were included,with 1424 patients,with a male to female ratio of 1.78:1.All the patients were younger than 18 years old and distributed in 7 regions including Taiwan(China)Italy,Japan and so on.The researches were published from 2002 to 2019.The follow-up time was 5 years or more.Univariate analysis of the survival curve drawn by kaplan-metier method was combined with meta-analysis.The 5-year survival rate of patients with st.Jude stage III and IV [HR=1.38,95%CI(1.02,1.87),P=0.04],immunophenotypic expression ofCD3[HR=1.97,95%CI(1.33,2.93),P=0.0008],bone marrow invasion [HR=2.17,95%CI(1.35,3.49),P=0.001] and skin invol [HR=1.38,95%CI(1.12,1.71),P=0.0034]were statistically different,suggesting these were poor prognostic factors.A combined meta-analysis based on Cox proportional risk model multi-factor analysis of the included study showed that bone marrow involvement [HR=2.60,95%CI(1.21,5.61),P=0.01] was an independent adverse prognostic factor.In addition,pathological types other than the normal type [HR=1.99,95%CI(1.37,2.83),P=0.0003],and serum LDH elevation [HR=1.86,95%CI(1.03,3.36),P=0.04] were also adverse prognostic factors affecting the survival rate of patients.ConclusionThe prognosis of pediatric and adolescent anaplastic large cell lymphoma is affcted by a variety of factors including St.Jude stage,histopathological type,immunophenotype,level of serum LDH,whether there are external involvement of lymph nodes,including mediastinal involvement,skin involvement and bone marrow involvement.Whether MDD is positive in bone marrow or peripheral blood,and whether there is high titer antibody against ALK gene in vivo.Stage Ⅲ and Ⅳ based on st.Jude stages,expression of CD3 on tumor cells,serum LDH level significantly elevates,pathological type is non-normal,and skin and bone marrow involvement are unfavorable prognostic factors affecting the survival rate.The pathologic type,bone marrow involvement and elevated serum LDH are adverse independent prognostic factors.