Peculiarities of Tumor Lysis Syndrome in Cancer Therapeutics – Chibuike Okafor

“When cancer treatment causes malignant cells to break down quickly and release their intracellular contents into the bloodstream, a potentially fatal oncological emergency known as tumor lysis syndrome (TLS) results. This unexpected spike has the potential to overburden the body’s metabolic and excretory systems, leading to acute kidney injury, cardiac arrhythmias, seizures, severe electrolyte imbalances, and potentially fatalities. Effective management of cancer patients depends on an understanding of the mechanisms underlying TLS, the medications that can cause it, and the countermeasures. 

Reasons behind Tumor Lysis Syndrome 

Treatment for hematological malignancies such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and high-grade lymphomas like Burkitt lymphoma is most frequently linked to TLS. Therapies that cause rapid death of tumor cells carry a heightened risk, such as: 

1. Cytotoxicity Chemotherapy: Cyclophosphamide, doxorubicin, and methotrexate are powerful inducers of cell lysis due to their ability to damage the DNA of rapidly dividing cells.
2. Targeted Therapy: In non-Hodgkin lymphoma, drugs such as rituximab, which targets the CD20 antigen on B-cells, can cause massive cell death.
3. Corticosteroids: High-dose corticosteroids can also cause TLS because they have a cytolytic effect on certain lymphoid malignancies.
4. Immunotherapy: Agents like CAR T-cell therapy, which involves engineering a patient’s T-cells to attack cancer cells, can cause tumor cells to lyse quickly and thoroughly.

TLS Pathophysiology 

TLS distinguishes itself by the release of intracellular ions and metabolic byproducts such as potassium, phosphate, and nucleic acids. Hyperuricemia can result from the degradation of nucleic acids into uric acid, whereas hyperphosphatemia and hyperkalemia are caused by increased levels of phosphate and potassium, respectively. These biochemical imbalances may lead to: 

– Renal Complications: Uric acid and calcium phosphate crystals can form in the renal tubules, causing acute kidney injury. 

– Cardiac Complications: Hyperkalemia can cause potentially fatal cardiac arrhythmias. 

– Neurological Complications: Hypocalcemia caused by hyperphosphatemia can result in tetany, seizures, and other neurological disorders. 

Prevention and Treatment of TLS 

Prevention, early detection, and timely intervention are critical components of effective TLS management. The following strategies are essential for combating the severe adverse effects of TLS: 

1. Risk stratification: Knowing the patient’s risk based on tumor type, burden, and baseline renal function allows you to tailor the prevention strategy.
2. Hydration and Diuresis: Administering intravenous fluids (2-3 liters/m²/day) before, during, and after chemotherapy improves renal perfusion and uric acid and phosphate excretion.
3. Allopurinol: As a xanthine oxidase inhibitor, allopurinol reduces the production of uric acid. It is especially effective when given prophylactically prior to chemotherapy.
4. Rasburicase: This recombinant urate oxidase enzyme converts uric acid into allantoin, a more soluble and easily excreted compound. Rasburicase is especially useful in high-risk patients or those who already have hyperuricemia.
5. Electrolyte Management: It is critical to closely monitor and correct electrolyte levels. Hyperkalemia may necessitate interventions such as insulin-glucose infusion, sodium bicarbonate, or calcium gluconate to stabilize cardiac membranes. Phosphate binders and dietary restriction can help treat hyperphosphatemia.
6. Renal Support: In cases of acute kidney injury, renal replacement therapy, such as hemodialysis, may be required to correct severe electrolyte imbalances and remove toxins.

Conclusion 

The management of TLS is a multidimensional approach that requires the integration of prophylactic measures, vigilant monitoring, and timely therapeutic interventions. Drugs like allopurinol and rasburicase play pivotal roles in preventing and treating hyperuricemia, thereby mitigating the renal complications of TLS. By understanding the complexities of TLS and implementing robust management protocols, clinicians can significantly reduce the morbidity and mortality associated with this syndrome, ensuring that cancer treatments are not only effective but also safe.” 

Written by Chibuike Okafor
Research Assistant at Department of Pharmaceutical/Medicinal Chemistry University of Jos

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