What is Tumor Lysis Syndrome?
Tumor lysis syndrome is a collection of metabolic abnormalities due to the tumor cell lysis in patients with treatment for malignancies.
Treatment of the cancer causes lysis of tumor cells which results in the release of the intracellular contents like electrolytes, nucleic acids and proteins. It leads to an increase in the levels of potassium, phosphate, uric acid and decrease in the calcium levels in the blood.
Tumor lysis syndrome is a complication in patients with treatment for cancer. The manifestation of the tumor lysis syndrome depends on various factors like the size of the tumor, the potential for tumor cell lysis, tumor chemosensitivity, supportive care and the patient health condition.
The cancers where the potential for cell lysis is more are
- High-grade lymphomas
- Acute leukemia
- Rapidly proliferating tumors
The patients with high risk to develop the tumor lysis syndrome are those with
- Pre-existing renal insufficiency
- Acidic urine
The signs and symptoms of tumor lysis syndrome are due to the release of intracellular contents.
- Hyperkalemia: It can cause cardiac arrhythmias and severe muscle weakness.
- Hyperphosphatemia: It causes renal failure due to deposition of calcium phosphate crystals.
- Hypocalcemia: Hypocalcemia can manifest with tetany, myopathy, dysrhythmias and seizures.
- Hyperuricemia: The cell lysis causes the release of the nucleic acids which are later converted to uric acid. The uric acid can cause acute renal failure due to acute uric acid nephropathy.
- Cytokines: The cytokines released during tumor lysis cause systemic inflammatory response syndrome and multi-organ failure.
Acute renal failure with increased serum uric acid and phosphorus in patients with cancer treatment suggests tumor lysis syndrome. Tumor lysis syndrome is classified based on laboratory findings and its clinical presentation.
Laboratory tumor lysis syndrome:
- Uric acid greater than 8mg/dl or 25% increase
- Potassium greater than 6meq/l or 25% increase
- Phosphate greater than 4.5mg/dl or 25% increase
- Calcium less than 7mg/dl or 25% decrease
Clinical tumor lysis syndrome:
- Creatinine greater than 1.5 times normal
- Cardiac arrhythmia/sudden death
This is a refinement of the standard Cairo-Bishop definition of TLS accounting for 2 limitations.
Two or more electrolyte abnormalities should be present at the same time so as to confirm that the variations are solely due to TLS.
The 25% change from baseline should not be considered as a criterion.
Recognizing the patients at risk of developing tumor lysis syndrome is important because it helps to take precautions before initiating the chemotherapy. Management of the tumor lysis syndrome includes preservation of renal function, prevention of arrhythmias and neuromuscular irritability. Early management of the tumor lysis syndrome is essential since the delay in the treatment can lead to the development of life-threatening complications.
Monitoring the blood levels of creatinine, potassium, uric acid, phosphorus, calcium, uric acid, sodium and LDH before and after the cancer therapy is essential. Monitoring the EKGs and heart during the therapy is essential. Adequate intravenous hydration for 1-2 days before the initiation of the therapy is important.
Fluids and Hydration: Adequate hydration is necessary to prevent and treat tumor lysis syndrome. The amount of IV fluids to hydrate is about 3L/m2/day.
Allopurinol: It is a hypouricemic agent which decreases the conversion of nucleic to uric acid. It should be given even before the initiation of the therapy.
Rasburicase: It promotes the degradation of the uric acid. It converts the uric acid to allantoin thereby decreasing the uric acid levels.
Renal Replacement Therapy: Dialysis is necessary for patients with acute kidney injury, severe electrolyte abnormalities and uremia due to tumor lysis syndrome.
Hypocalcemia: Administration of intravenous calcium gluconate if there is a significant decrease in calcium.
- Howard, S. C., Jones, D. P., & Pui, C.-H. (2011). The tumor Lysis Syndrome. The New England Journal of Medicine, 364(19), 1844–1854. http://doi.org/10.1056/NEJMra0904569
- Tumor Lysis Syndrome - (http://www.haematologica.org/content/93/1/9)
- Tumor lysis syndrome: current perspective - (https://www.asn-online.org/education/distancelearning/curricula/onco/Chapter4.pdf)
Latest Publications and Research on Tumor Lysis Syndrome
- Tumour lysis syndrome in patients with chronic lymphocytic leukaemia treated with BCL-2 inhibitors: risk factors, prophylaxis, and treatment recommendations. - Published by PubMed
- Co-existence of follicular lymphoma in the lymph node with High-grade B cell lymphoma in the bone marrow of a patient presenting with spontaneous tumor lysis syndrome. - Published by PubMed
- Anti-rasburicase antibodies induce clinical refractoriness by inhibiting the enzyme catalytic activity. - Published by PubMed
- Cytogenetics and mutations could predict outcome in relapsed and refractory acute myeloid leukemia patients receiving BCL-2 inhibitor venetoclax. - Published by PubMed
- Acute Liver Failure as the Leading Manifestation of Spontaneous Tumour Lysis Syndrome in a Patient with NonHodgkin Lymphoma: Do Current Diagnostic Criteria of Tumour Lysis Syndrome Need Re-Evaluation? - Published by PubMed
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