An explorative analysis of the 3060 patients for whom ISS, CA and LDH data were simultaneously available was conducted. The K-adaptive partitioning,25 dedicated to censored survival data (minimax-based partitioning rule by log-rank test), was used for ISS/CA/LDH grouping: this routine gave an optimal number of three subgroups: the R-ISS I, II and III. The OS and PFS curves were estimated by the Kaplan-Meier method and compared by the log-rank test. OS and PFS were then analyzed through the Cox proportional hazards model, comparing the following risk factors by the Wald test: age at diagnosis (≤65 vs >65 years), gender (male vs female), iFISH (high-risk vs standard-risk CA), LDH (high vs normal), ISS (II vs I and III vs I) and R-ISS grouping as defined by the recursive partitioning procedure. The effects of the baseline features (age, gender and R-ISS) were also assessed by the multivariate Cox model; as in the univariate analysis, the R-ISS stage was treated as time-dependent variable. Subgroup analyses of PFS and OS were performed to confirm the effect of R-ISS in different subgroups of patients, that is in patients older and younger than 65 years of age, and in patients receiving ASCT or not, those receiving PI or not and those receiving IMIDs or not. Patients characteristics were tested using the Fisher’ exact test for categorical variables and the Mann-Whitney test for continuous ones. All reported p-values were two-sided, at the conventional 5% significance level. Data were analyzed as of December 2014 by R 3.0.1 package kaps and IBM SPSS 21.0.0.