Pretreatment Hemoglobin as an Independent Prognostic Factor in Primary Central Nervous System Lymphomas

Abstract

Background Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma. Despite established clinical prognostic scoring such as that of the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Extranodal Lymphoma Study Group, outcome prediction needs to be improved. Several studies have indicated an association between changes in hematologic laboratory parameters with patient outcomes in PCNSL. We sought to assess the association between hematological parameters and overall survival (OS) in patients with PCNSL. Methods Pretreatment blood tests were analyzed in patients with newly diagnosed PCNSL (n = 182), and we divided the analysis into two cohorts (A and B, both n = 91). OS was evaluated using the Cox proportional hazards models and log‐rank test. Furthermore, the accuracy of the different multivariate models was assessed by Harrell's concordance index (C‐index). Results Using prechemotherapy blood tests, anemia was found in 38 patients (41.8%) in cohort A and 34 patients (37.4%) in cohort B. In univariate analysis, anemia (<12 g/dL in women and <13 g/dL in men) was significantly associated with OS. None of the other blood tests parameters (neutrophils, lymphocyte, or platelets counts) or their ratios (neutrophil‐to‐lymphocyte ratio and neutrophil‐to‐platelets ratio) were associated with OS. In multivariate analysis, after adjusting by MSKCC score, anemia remained an independent prognostic factor. Interestingly, the prediction accuracy of OS using Harrell's C‐index was similar using anemia or MSKCC (mean C‐index, 0.6) and was increased to 0.67 when combining anemia and MSKCC. Conclusion The presence of anemia was associated with poor prognosis in both cohorts of PCNSL. Validation of these results and biologic role of hemoglobin levels in PCNSL requires further investigation. Implications for Practice The prediction of the outcome of primary central nervous system lymphoma (PCNSL) using the most frequently used scores (i.e., Memorial Sloan Kettering Cancer Center [MSKCC] or International Extranodal Lymphoma Study Group) needs to be improved. We analyzed a large cohort of PCNSL to dissect the potential prognostic value of blood tests in this rare entity. We found anemia as an independent predictor for overall survival in PCNSL. Interestingly, the accuracy to predict PCNSL outcome was improved using hemoglobin level. This improvement was additional to the currently used clinical score (i.e., MSKCC). Finally, none of the other blood tests parameters or their ratios had a prognostic impact in this study.

Prognostic Role of Blood Markers in Primary Central Nervous System Lymphoma Patients Treated With High-Dose Methotrexate-Based Therapy

“…Taken together, we evaluated that cytokine alternations in PCNSL may play a role for anemia. In parallel with a PCNSL study based on European populations which found that pretreatment anemia ( defined as <12 g/dl in women and <13 g/dl in men) was robustly associated with poor prognosis ( 26 ), our study had a different cutoff value of ≤11.1 g/dl in all patients and found that patients with a low Hb level had an inferior outcome in PFS. But the cutoff for OS was 15 g/dl, which achieved maximum log-rank statistic and was not statistically significant in univariate analysis.…”

“…The negative prognostic role of a low Hb level has been widely investigated in the solid and hematologic malignancies including PCNSL ( 14 , 25 , 26 ). Cytokines including interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-10 (IL-10) have been demonstrated to inhibit the function of erythropoietin in vivo , and high IL-6 levels were thought to be the major factor for the development of anemia in DLBCL ( 27 , 28 ); likewise, an elevated CSF level of IL-10 in PCNSL was associated with a shorter PFS ( 29 ).…”

A new prognostic score for disease progression and mortality in patients with newly diagnosed primary CNS lymphoma

“…To evaluate the prognostic impact of other readily available parameters, we added hemoglobin, C‐reactive protein, and bilirubin levels into our analysis. Nevertheless, we did not detect significant correlation between these factors and clinical outcomes in this study.…”

<p>The Neutrophil to Lymphocyte and Lymphocyte to Monocyte Ratios as New Prognostic Factors in Hematological Malignancies – A Narrative Review</p>

“…73 In contrary to the studies mentioned above, Le at al. 74 reported that neither neutrophils, lymphocyte, or platelets counts nor their ratios (neutrophil-tolymphocyte ratio and neutrophil-to-platelets ratio) predicted OS. Interestingly, the only factor associated with OS was pretreatment hemoglobin.…”