Cancer's Metabolic Hijack: The Under-Recognized Hematologic Emergency Related to the Warburg Effect.

The Warburg effect, also referred to as aerobic glycolysis, describes the dysregulated energy metabolism in cancer cells with rewired energy generation, which is the hallmark of metabolic shift in cancer. It is a sign of "acute cancer" and is correlated with high malignancy burden and potential aggressive leukemia transformation in lymphoma. We present a case of T-cell lymphoma that developed into life-threatening clinical syndrome driven by the Warburg effect manifesting as severe type B lactic acidosis and refractory hypoglycemia. A 39-year-old female with a history of NK T-cell lymphoma and airway narrowing secondary to bulky cervical lymphadenopathy presented with fever after recent chemotherapy. She had developed a high fever on day eight of her second cycle of chemotherapy. On presentation, she reported neck pain and generalized fatigue; her peak temperature was 38.9 °C (101.5 °F), but she was hemodynamically stable. Physical examination revealed bulky axillary lymphadenopathy. Laboratory findings revealed pancytopenia, lactic acid of 4.9 mmol/L, and glucose of 57 mg/dL. She received a blood transfusion and empiric antibiotics. Interestingly, she developed refractory hypoglycemia that did not respond to standard treatment. Despite being on an infusion of dextrose 10% at the rate of 100 ml/hour and repeat pushes of dextrose 50%, she continued to experience drops in blood glucose levels into the 40s six times. Extensive workup ruled out active infection, insulinoma, and factitious use of anti-diabetic drugs. She was transferred to the ICU due to worsening lactic acidosis and refractory hypoglycemia; her lactic acid peaked at 14.40 mmol/L. At first glance, it was puzzling as to why she was hypoglycemic despite being switched to dextrose 20% infusion at 150 ml/hour in the ICU. Her blood glucose dropped below 70 mg/dL multiple times and required repeated pushes of dextrose 50%, but her blood glucose still kept dropping. Our review of the literature revealed that this classic clinical syndrome is driven by the Warburg effect - an ominous sign of aggressive leukemia transformation and high tumor burden. The patient's clinical status rapidly deteriorated and she was intubated for impending respiratory distress, complicated by life-threatening bleeding due to disseminated intravascular coagulation (DIC) and malignant high fever. In light of the extremely poor prognosis, her family decided to withdraw aggressive care, and the patient expired the same night after the withdrawal of care. The classic clinical syndrome driven by the Warburg effect can be an early sign of impending clinical decompensation, and early recognition enables clinicians to appreciate the grim nature of the illness and initiate prompt chemotherapy to improve outcomes. As a hallmark of tumor cells, the Warburg effect has also become a promising therapeutic target in cancer treatment.