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ABSTRACT Introduction: The diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) and, despite all the progress in this field, central nervous system infiltration (CNSi) still occurs at an incidence of 2-10%. The objective of the present study was to evaluate the Central Nervous System International Prognostic Index (CNS-IPI) score in daily practice regarding the reproducibility in a heterogeneous cohort apart from a clinical trial. Methods: Primary DLBCL patients were eligible for this study, between January 2007 and January 2017. All patients were treated with rituximab-based chemotherapy, mostly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). The CNSi was diagnosed by liquor (positive cytology and/or immunophenotype), computerized tomography, magnetic resonance image and/or fluorodeoxy-glucose-positron emission tomography, requested only in symptomatic patients when the CNSi was clinically suspected. The CNS-IPI was assessed by graphical comparison and calibration. Results: After applying the inclusion/exclusion criteria, 322 patients were available for the analysis. The median follow-up was 60 months and the median age was 58 years. Seven patients experienced CNSi, characterizing an incidence of 2.17% (7/322). Comparing groups of patients with and without CNSi, we observed that the lactate dehydrogenase (LDH), number of extranodal sites, IPI, kidney/adrenal and absence of complete response were statistically different. The CNS-IPI model stratified patients in a three-risk group model as low-, intermediate- and high-risk. In our cohort, using the same stratification, we obtained an equivalent the 2-year rate of CNS relapse of 0.0%, 0.8% and 13.8%, respectively. Conclusion: Our study reinforces the reproducibility of the CNS-IPI, specifically apart from clinical trials, and suggests the CNS-IPI score as a tool to guide therapy. Introduction Bcell B cell (DLBCL nonHodgkin non Hodgkin NHL (NHL field (CNSi 210%. 210 2 10%. 10 2-10% CNSIPI IPI (CNS-IPI trial Methods 200 2017 rituximabbased rituximab based chemotherapy RCHOP R CHOP rituximab, (rituximab cyclophosphamide doxorubicin prednisone. prednisone . prednisone) positive andor or immunophenotype, immunophenotype , immunophenotype) tomography fluorodeoxyglucosepositron fluorodeoxy glucose positron suspected calibration Results inclusionexclusion inclusion exclusion criteria 32 analysis followup follow up 6 5 years 217 17 2.17 7/322. 7322 7/322 7 (7/322) LDH, LDH (LDH) sites kidneyadrenal kidney adrenal different threerisk three risk low, low low- intermediate highrisk. highrisk high risk. high-risk stratification 2year year 00 0 0.0% 08 8 0.8 138 13 13.8% respectively Conclusion CNSIPI, trials therapy 210% 21 10% 1 2-10 20 201 3 2.1 732 7/32 (7/322 (LDH 0.0 0. 13.8 2-1 2. 73 7/3 (7/32 13. 2- 7/ (7/3 (7/ (7 (