Clinical Warburg effect in lymphoma patients admitted to intensive care unit

Anis Chaba; Sofiane Fodil; Virginie Lemiale; Eric Mariotte; Sandrine Valade; Elie Azoulay; Lara Zafrani

doi:10.1186/s13613-023-01192-z

Clinical Warburg effect in lymphoma patients admitted to intensive care unit

Ann Intensive Care. 2023 Oct 5;13(1):97. doi: 10.1186/s13613-023-01192-z.

Authors

Anis Chaba¹, Sofiane Fodil², Virginie Lemiale¹, Eric Mariotte¹, Sandrine Valade¹, Elie Azoulay^{1

3}, Lara Zafrani^{4

5

6}

Affiliations

¹ Medical Intensive Care Unit, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75010, Paris, France.
² Department of Hematology, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
³ University Paris Cité, Paris, France.
⁴ Medical Intensive Care Unit, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75010, Paris, France. lara.zafrani@aphp.fr.
⁵ University Paris Cité, Paris, France. lara.zafrani@aphp.fr.
⁶ INSERM, UMR 944, University Paris Cité, Paris, France. lara.zafrani@aphp.fr.

Abstract

Background: The Warburg effect, characterized by elevated lactate levels without tissue hypoxia or shock, has been described in patients with aggressive lymphoproliferative malignancies. However, the clinical characteristics and long-term outcomes in this population remain poorly understood.

Methods: We retrospectively analyzed 135 patients with aggressive lymphoproliferative malignancies admitted to the ICU between January 2017 and December 2022. Patients were classified into three groups: Clinical Warburg Effect (CWE), No Warburg with High Lactate level (NW-HL), and No Warburg with Normal Lactate level (NW-NL). Clinical characteristics and outcomes were compared between the groups and factors associated with 1-year mortality and CWE were identified using multivariable analyses.

Results: Of the 135 patients, 46 (34%) had a CWE. This group had a higher proportion of Burkitt and T cell lymphomas, greater tumor burden, and more frequent bone and cerebral involvement than the other groups. At 1 year, 72 patients (53%) died, with significantly higher mortality in the CWE and NW-HL groups (70% each) than in the NW-NL group (38%). Factors independently associated with 1-year mortality were age [HR = 1.02 CI 95% (1.00-1.04)], total SOFA score at admission [HR = 1.19 CI 95% (1.12-1.25)], and CWE [HR = 3.87 CI 95% (2.13-7.02)]. The main factors associated with the CWE were tumor lysis syndrome [OR = 2.84 CI 95% (1.14-7.42)], bone involvement of the underlying malignancy [OR = 3.58 CI 95% (1.02-12.91)], the total SOFA score at admission [OR = 0.81 CI 95% (0.69-0.91)] and hypoglycemia at admission [OR = 14.90 CI 95% (5.42-47.18)].

Conclusion: CWE is associated with a higher tumor burden and increased 1-year mortality compared to patients without this condition. Our findings underscore the importance of recognizing patients with CWE as a high-risk cohort, as their outcomes closely resemble those of individuals with lymphoma and shock, despite not requiring advanced organ support. Clinicians should recognize the urgency of managing these patients and consider early intervention to improve their prognosis.

Keywords: Intensive care unit; Lactate; Lymphoma; Warburg effect.