Katharina T Troppan1, Thomas Melchardt2, Alexander Deutsch1, Konstantin Schlick2, Tatjana Stojakovic3, Marc D Bullock4, Daniel Reitz5, Christine Beham-Schmid6, Lukas Weiss2, Daniel Neureiter7, Kerstin Wenzl1, Richard Greil2, Peter Neumeister1, Alexander Egle2, Martin Pichler4,5. 1. Division of Hematology, Medical University of Graz (MUG), Graz, Austria. 2. 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. 3. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz (MUG), Graz, Austria. 4. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 5. Division of Oncology, Medical University of Graz (MUG), Graz, Austria. 6. Institute of Pathology, Medical University of Graz (MUG), Graz, Austria. 7. Institute of Pathology, Paracelsus Medical University Salzburg, Salzburg, Austria.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Michael R Clausen; Matthew J Maurer; Sinna Pilgaard Ulrichsen; Thomas S Larsen; Bodil Himmelstrup; Dorthe Rønnov-Jessen; Brian K Link; Andrew L Feldman; Susan L Slager; Grzegorz S Nowakowski; Carrie A Thompson; Per Trøllund Pedersen; Jakob Madsen; Robert S Pedersen; Jette Sønderskov Gørløv; James R Cerhan; Mette Nørgaard; Francesco D'Amore Journal: Clin Epidemiol Date: 2019-11-14 Impact factor: 4.790