What is the relationship between splenic lymphoma and lactic acidosis?

From the Guidelines

Splenic lymphoma with lactic acidosis is a medical emergency that requires immediate intervention with chemotherapy and management of the metabolic disturbances, as evidenced by the high incidence of tumor lysis syndrome in patients with hematologic malignancies, including non-Hodgkin's lymphoma (NHL) 1.

Clinical Presentation and Risk Factors

The presentation of splenic lymphoma with lactic acidosis can be complex, involving both the direct effects of the lymphoma on the spleen and the systemic effects of lactic acidosis. The risk factors for tumor lysis syndrome (TLS), which can include lactic acidosis, are well-documented in patients with high-grade NHL, with rates as high as 42% in some studies 1. The development of TLS is particularly concerning, as it can lead to life-threatening complications, including renal failure and cardiac arrhythmias.

Management and Treatment

The management of splenic lymphoma with lactic acidosis should focus on:

• Rapid initiation of chemotherapy appropriate for the lymphoma subtype, such as R-CHOP for B-cell lymphomas.
• Concurrent management of lactic acidosis through IV fluid resuscitation, correction of electrolyte abnormalities, and possible bicarbonate administration for severe acidosis.
• Tumor lysis prophylaxis with allopurinol or rasburicase, especially in patients with high tumor burden.
• Close monitoring in an ICU setting with serial lactate measurements, comprehensive metabolic panels, and complete blood counts.

Pathophysiology and Prognosis

The connection between splenic lymphoma and lactic acidosis is thought to be related to the Warburg effect, where rapidly proliferating lymphoma cells preferentially use glycolysis, producing excess lactate 1. Additionally, liver infiltration by lymphoma may impair lactate clearance, contributing to the development of lactic acidosis. The prognosis depends on rapid diagnosis and treatment initiation, as untreated cases have high mortality rates. In select cases, splenectomy may be considered for both diagnostic and therapeutic purposes if the patient is stable enough for surgery.

Key Considerations

• The incidence of hyperuricemia and TLS in patients with acute leukemia or NHL is significant, with rates of 18.9% and 5.0%, respectively 1.
• The rates of TLS are higher in certain subgroups, such as patients with Burkitt’s lymphoma or Burkitt’s ALL, highlighting the need for prompt recognition and management of TLS in these patients.
• The use of prophylactic measures, such as IV hydration and allopurinol, can help reduce the risk of TLS in patients undergoing initial induction chemotherapy for AML 1.

From the Research

Splenic Lymphoma and Lactic Acidosis

• Splenic lymphoma has been associated with lactic acidosis, particularly type B lactic acidosis, which occurs in the absence of tissue hypoxia or hypoperfusion 2, 3, 4, 5.
• The mechanism behind this association is thought to be related to the "Warburg effect," where cancer cells switch their glucose metabolism to increasingly anaerobic glycolytic phenotypes, leading to increased lactic acid production 3, 5.
• Studies have reported cases of patients with splenic lymphoma or other hematologic malignancies presenting with type B lactic acidosis, which is often refractory to treatment with bicarbonate or other alkali therapies 2, 3, 4, 5.
• Treatment of the underlying malignancy with chemotherapy, such as rituximab, is often necessary to resolve the lactic acidosis 2, 3, 6, 5.
• The prognosis for patients with malignancy-related type B lactic acidosis is generally poor, highlighting the importance of early diagnosis and treatment 3, 4, 5.

Clinical Presentation

• Patients with splenic lymphoma and lactic acidosis may present with nonspecific symptoms, such as tachypnea, pancytopenia, and elevation of IgM levels 2.
• Laboratory tests may show metabolic acidosis, high lactic acid levels, and anion gap metabolic acidosis 2, 3, 4.
• Imaging studies, such as abdominal CT scans, may reveal splenic lesions or other signs of lymphoma 4, 6.

Treatment

• Chemotherapy, such as rituximab, is often effective in treating the underlying malignancy and resolving the lactic acidosis 2, 3, 6, 5.
• Alkali therapy, such as bicarbonate, may be used to treat severe acidemia, but its role is controversial and may have limited benefit 5.
• Early diagnosis and treatment of the underlying malignancy are crucial to improve outcomes in patients with splenic lymphoma and lactic acidosis 3, 4, 5.