title: The significance of pretreatment anemia in the era of R-IPI and NCCN-IPI prognostic risk assessment tools: a dual-center study in diffuse large B-cell lymphoma patients.
abstract: BACKGROUND
  Anemia is frequently identified at the time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL); however, studies addressing the prognostic significance of this important clinical parameter are lacking.
  
  
  METHODS
  In this dual-center study of patients with DLBCL (n = 556) treated with rituximab-containing regimens, we evaluated the prognostic relevance of anemia at diagnosis in a training set (n = 211) and validated our findings in a second independent patient cohort (n = 345). Using Kaplan-Meier curves as well as univariate and multivariate Cox regression models, we analyzed the impact of anemia on 5-year overall survival (OS) and 5-year disease-free survival (DFS) alongside established prognostic indicators including age, tumor stage, the revised International Prognostic Index (R-IPI), and the recently published NCCN-IPI. The influence of anemia on the predictive accuracy of IPI, R-IPI, and NCCN-IPI prognosis scores was subsequently determined using the Harrell's concordance index.
  
  
  RESULTS
  Anemia was an independent predictor of impaired OS and DFS at 5 years in both DLBCL patient cohorts (P < 0.001, log-rank test). In multivariate analysis, hemoglobin level was also a strong and independent prognostic indicator in patients stratified according to R-IPI or NCCN-IPI score. In survival analysis, the estimated concordance index, using IPI, R-IPI, and NCCN-IPI stratification measures (0.69, 0.64, and 0.70, respectively), improved to 0.70, 0.68, and 0.73, respectively, when anemia was also considered.
  
  
  CONCLUSIONS
  In this study, we have demonstrated that anemia at the time of diagnosis is an independent predictor of impaired clinical outcome in DLBCL. Furthermore, consideration of hemoglobin levels may improve the accuracy of recently established prognostic tools in lymphoma. Our data encourage further evaluation of the prognostic utility of this readily accessible biological parameter in prospective clinical trials.
authors: Division of Hematology, Medical University of Graz (MUG), Graz, Austria.
authors: Katharina T
authors: KT
authors: Troppan
authors: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors: Thomas
authors: T
authors: Melchardt
authors: Division of Hematology, Medical University of Graz (MUG), Graz, Austria.
authors: Alexander
authors: A
authors: Deutsch
authors: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors: Konstantin
authors: K
authors: Schlick
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz (MUG), Graz, Austria.
authors: Tatjana
authors: T
authors: Stojakovic
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Marc D
authors: MD
authors: Bullock
authors: Division of Oncology, Medical University of Graz (MUG), Graz, Austria.
authors: Daniel
authors: D
authors: Reitz
authors: Institute of Pathology, Medical University of Graz (MUG), Graz, Austria.
authors: Christine
authors: C
authors: Beham-Schmid
authors: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors: Lukas
authors: L
authors: Weiss
authors: Institute of Pathology, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors: Daniel
authors: D
authors: Neureiter
authors: Division of Hematology, Medical University of Graz (MUG), Graz, Austria.
authors: Kerstin
authors: K
authors: Wenzl
authors: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors: Richard
authors: R
authors: Greil
authors: Division of Hematology, Medical University of Graz (MUG), Graz, Austria.
authors: Peter
authors: P
authors: Neumeister
authors: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors: Alexander
authors: A
authors: Egle
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Division of Oncology, Medical University of Graz (MUG), Graz, Austria.
authors: Martin
authors: M
authors: Pichler
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000401:mortality*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004909:Erythrocyte Indices; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D016016:Proportional Hazards Models
keywords: diffuse large B-cell lymphoma; hemoglobin; prognostic factors