Tumor-Associated Lactic Acidosis and Early Death in Patients With Lymphoma

Abstract

Background: Cancer is characterized by accelerated glycolysis with enhanced glucose uptake and lactate production, a phenomenon termed Warburg effect (WE). We studied the incidence and clinical impact of Warburg-driven lactic acidosis in lymphoma.

Methods: Patients admitted with newly diagnosed or relapsed/refractory lymphoma and documented lactate levels during the first week of admission were included. Patients with lactatemia were classified as secondary (with a recognizable cause for elevated lactate) or none (WE group).

Results: WE and secondary lactatemia were documented in 58 and 44 patients (15% and 12% of evaluable patients, respectively). Both WE and secondary lactatemia were associated with poor short-term survival. WE at presentation correlated with tumor burden, with most patients having aggressive disease, advanced stage, and extranodal involvement. WE was associated with high rates of early death (26% and 43% at 30- and 60-days, respectively). Higher lactate levels correlated with worse survival. Earlier initiation of chemotherapy was associated with a (nonsignificant) trend toward better outcomes, whereas steroid and/or thiamine therapy did not alter patient outcomes. Glucose administration was associated with worse survival.

Conclusion: WE-driven lactatemia is associated with high tumor burden and increased short-term mortality in lymphoma. Prompt initiation of anti-lymphoma therapy may improve outcomes.

Keywords: Warburg effect; early death; lactatemia; lymphoma.