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.

Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma

“…However, until now no data are available to support escalation or de‐escalation of treatment based on IPI score alone. Furthermore, the IPI is unable to predict the response to novel agents and fails to clearly identify or distinguish high and very high‐risk groups 15,16 . Thus, there is a real need to improve its prognostic capabilities.…”

Decreased Serum Bilirubin Levels and Increased Uric Acid Levels are Associated with Ulcerative Colitis

“…UA was once thought to be an intracellular free radical scavenger [ 30 ] which possessed antioxidative properties [ 31 , 32 ]. However, increasing epidemiological evidence suggests that a role for hyperuricemia in the occurrence and progression of cardiovascular diseases [ 12 , 13 ], chronic kidney disease [ 10 , 33 ], diabetes mellitus [ 34 ], metabolic syndrome [ 35 ], malignant neoplasms [ 36 , 37 ] and even IBD [ 38 ]. The association of UA with the risk of suffering the aforementioned diseases could be partly explained by its pro-oxidant and proinflammatory properties.…”

Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

“…A high SUA level was associated with a poor prognosis in acute myelocytic leukemia patients [29]. It was demonstrated that diffuse, large B-cell lymphoma patients having elevated SUA levels showed consistently worse conditional survival outcomes when compared with patients with lower uric acid levels, with their conditional outcomes only approaching those of the lower uric acid patients approximately 5 years after diagnosis [30]. As for respiratory organs, it has been found that among the non-small cell lung cancer patients who had higher SUA levels; there was a higher percentage of brain metastasis, and a shorter time until brain metastasis and lower overall survival [31].…”