title: NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients.
abstract: BACKGROUND
  Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL.
  
  
  METHODS
  The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival.
  
  
  RESULTS
  Five-year OS and PFS were 50.4% (95% CI: 39.2-60.6) and 44.0% (33.4-54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl-1), and 66.2% (60.4-71.5) and 59.6% (53.7-65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10-1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16-2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17-9.23, P<0.0001).
  
  
  CONCLUSIONS
  We demonstrate that elevated uric acid levels predict poor long-term outcomes in DLBCL patients beyond the NCCN-IPI risk index.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz (MUG), Graz 8036, Austria.
authors.forename: Katharina T
authors.initials: KT
authors.lastname: Prochazka
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Melchardt
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz 8036, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Posch
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Schlick
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz (MUG), Graz 8036, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Deutsch
authors.affiliation: Institute of Pathology, Medical University of Graz (MUG), Graz 8036, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Beham-Schmid
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Weiss
authors.affiliation: Division of Angiology, Department of Internal Medicine, Medical University of Graz (MUG), Graz 8036, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gary
authors.affiliation: Institute of Pathology, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.affiliation: Institute of Pathology, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Klieser
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz (MUG), Graz 8036, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Neumeister
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Paracelsus Medical University Salzburg, Salzburg 5020, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Egle
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz 8036, Austria.|Research Unit for non-coding RNAs and genome editing in cancer, Graz 8036, Austria.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001317:Austria; D014408:Biomarkers, Tumor / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use*; D014527:Uric Acid / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D014527:Uric Acid; D000069283:Rituximab