A 30 year-old woman presents with abdominal pain , vomiting and paraesthesiae. She was diagnosed with CML 2 months previously, and was started on chemotherapy 4 weeks ago. Her last chemo was 3 days ago. Her lab results are as followed:

Answers: 1

1. Mild hyponatremia
2. Moderate Hyperkalaemia
3. Hyperphosphataemia
4. Hypocalcaemia
5. Hyperuricaemia
6. High creatinine and urea consistent with renal impairment, with a high urea-to-creatinine ratio
7. Low HCO3 consistent with metabolic acidosis (lactate is normal)
8. High lactate dehydrogenase (LDH)

2:

• This constellation of laboratory abnormalities, in a patient receiving chemotherapy for a hematological malignancy, is characteristic of Tumour Lysis Syndrome (TLS)

Pathophysiology:

• Hyperkalaemia is due to rapid expulsion of potassium into the circulation due to cell lysis, and may result in lethal dysrhythmias
• Hyperphosphataemia is due to release of intracellular phosphate due to lysis of tumour cells
• Hypocalcaemia results from a rapid increase in phosphate concentration leading to precipitation of calcium, and may cause tetany and neuromuscular irritability
• Hyperuricaemia is due to increased levels of purine nucleotides into the circulation that are metabolized to uric acid
• Renal failure is multi factorial and is thought to results from a combination of dehydration, uric acid nephropathy and calcium phosphate nephropathy

Lactic acidosis can also be seen in TLS, but is not present in this case.

Tumour lysis syndrome is most commonly associated with:

• poorly differentiated lymphomas, e.g. Burkitt’s lymphoma and high-grade non-Hodgkin lymphomas
• leukemia, e.g. acute myeloid leukemia (AML), transformed chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL)
• some fast-growing solid tumours such as hepatocellular carcinoma, hepatoblastoma, testicular cancer, small cell lung cancer, breast cancer and neuroblastoma.

TLS typically occurs about 48-72 hours after chemotherapy is commenced, but spontaneous TLS can also occur (e.g. aggressive lymphomas and leukemias such as Burkitt lymphoma, acute lymphocytic leukemia, large T-cell lymphoma) or it may occur after other cancer treatments (e.g. corticosteroids or radiotherapy).

Hyperphosphatemia tends not to occur in spontaneous TLS, presumably because the phosphate is recycled in the synthesis of new tumour cells (which does not occur when chemotherapy is used).

Pre-existing renal failure may also be a predisposing factor.

3.  Main stay of treatment is good supportive care.

• Medical treatment of hyperkalaemia proceeds according to normal guidelines.
• Aggressive rehydration is required (e.g. continue at twice the maintenance rate)
• Urinary alkalinisation can be used to decrease uric acid precipitation;
• phosphate and xanthine crystals.
• Phosphate binders can be given.
• Renal replacement therapy is required for refractory cases.
• Administration of calcium can worsen calcium phosphate precipitation. Hypocalcaemia should not treated unless symptomatic, in which administer 10% calcium gluconate.