Prognostic Factors And Nomogram For Survival Prediction In Patients With ALK-positive Anaplastic Large Cell Lymphoma

ObjectiveAnaplastic large cell lymphoma,anaplastic lymphoma kinase positive(ALK+ALCL)is classified as a non-Hodgkin lymphoma of T-cell origin by the World Health Organization(WHO)with strong expression of CD30,but it has superior prognosis than other peripheral T cell lymphomas.This study is designed to investigate prognostic factors associated with ALK+ALCL,and to establish a reliable nomogram for predicting the overall survival(OS)rates of ALK+ALCL.MethodsA total of 1602 patients diagnosed with ALK+ALCL from January 2004 to December 2015 in the Surveillance,Epidemiology,and End Results(SEER)database were included.They were randomly divided into a training cohort(n=1122)and a validation cohort(n=480)by simple randomization.Kaplan-Meier(K-M)method was used to analyze the survival of the population and subgroups divided by the clinical characteristics and treatment regimens.In the training cohort,univariate and multivariate analyses of the Cox proportional hazards regression were performed on the clinical characteristics including gender,age,Ann Arbor stage,systemic symptoms,primary site,and race that might potentially impact OS.Based on the Cox proportional hazards regression analysis,independent prognostic factors were selected to establish 3-year,5-year,and 10-year OS Nomogram of ALK+ALCL.The discrimination and calibration of nomogram were evaluated using the Concordance index(C index),Receiver operating characteristic(ROC)analysis and calibration curves.Its accuracy and benefits were assessed by comparing it to Ann Arbor stage using net reclassification improvement(NRI),integrated discrimination improvement(IDI),and decision curve analysis(DCA).ResultsThe K-M analysis showed that the overall median survival of the whole cohort was not reached,and the 3-year,5-year,and 10-year OS rates were 63.7%,60.9%and 54.6%,respectively.Older age,male,race of black,systemic symptoms and advanced stage made ALK+ALCL patients live shorter,but primary cutaneous ALK+ALCL patients with limited stage(stage I accounting for about 74.2%)had better prognosis with 5-year OS of 82.7%.Multivariate Cox proportional hazards regression analysis suggested that age,gender,systematic symptoms,Ann Arbor stage and primary site were significantly independent factors.Compared with Ann Arbor stage,the C index(training cohort:0.726 vs.0.597,validation cohort:0.777 vs.0.639),the area under the receiver operating characteristic curve(AUC)of the training cohort(3-year AUC:0.758 vs.0.620,5-year AUC:0.761 vs.0.614,10-year AUC:0.798vs.0.585),the validation cohort(3-year AUC:0.819 vs,0.672,5-year AUC:0.832 vs.0.656,10-year AUC:0.838 vs.0.645)and the calibration plots all indicated that the nomogram had better predicted ability.Additionally,the NRI and IDI confirmed so.In addition,the 3-,5-,and 10-year DCA indicated that the nomogram won larger net benefits than Ann Arbor stage.ConclusionAge,sex,systemic symptoms,Ann Arbor stage,and primary site were independent prognostic factors significantly affecting OS on ALK+ALCL patients.Primary cutaneous ALK+ALCL patients were mainly in the limited stage with a better prognosis.We have successfully established an effective nomogram to predict OS of individuals diagnosed with ALK+ALCL,which can be used to evaluate the prognosis of patients before treatment,so as to further guide clinical practice.