Tumour Lysis Syndrome

OVERVIEW

• oncological emergency due to turnover of high cell mass malignancies resulting in severe metabolic derangement

HISTORY

• lymphoproliferative malignancy + chemotherapy, radiotherapy or corticosteroids
• can occur spontaneously
• normally 12-72h hours post chemo

• GI upset
• oedema
• fluid overload
• haematuria
• symptoms of metabolic derangements (see below)

RISK FACTORS

• large tumour burden
• LDH > 1500 IU
• extensive marrow involvement
• high tumour sensitivity to chemotherapeutic agents
• ALL
• Burkitt lymphoma
• chemotherapy – cisplatin, etoposide, fludarabine, intrathecal methotrexate, paclitaxel, ritiuximab, radiation, interferon, corticosteroids, tamoxifen

Tumours that cause TLS include:

• poorly differentiated lymphomas, e.g. Burkitt 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

Usually occurs 12-72 hours after chemotherapy but can occur spontaneously (usually less hyperphosphatemia in this case, presumably due to recycling of phosphate)

EXAMINATION

• arrhythmias -> haemodynamically unstable
• weakness
• paraesthesia
• tetany
• renal failure

INVESTIGATIONS

Metabolic derangement

• Hyperkalaemia
• Hyperphosphataemia
• Hypocalcaemia
• Hyperuricaemia
• High creatinine and urea consistent with renal impairment
• Low HCO3 consistent with metabolic acidosis +/- hyperlactemia
• High lactate dehydrogenase (LDH)

MANAGEMENT

Prevention

• identify those at risk
• hydration (pre chemotherapy)
• monitoring of electrolytes
• allopurinol

General Management of TLS

Establish severity using the Cairo-Bishop classification

1. hydration – aggressive +/- diuretics
2. metabolic correction
3. support of renal failure

Hyperuricemia

• > 476 micromol/L or 25% increase from baseline
• cell lysis -> increased purine nucleic acids into the circulation -> metabolized to uric acid -> renal failure

(1) inhibit the formation of uric acid -> hydration, xanthine oxidase inhibitors (allopurinol – up to 800mg/day), urate oxidase/rasburicase (catalyzes oxidation of uric acid to allantoin), no evidence for alkalinisation of urine
(2) increasing renal clearance -> dialysis

Hyperkalaemia

• >6.0 mmol/L or increase in 25% from baseline
• rapid expulsion of intracellular K+ into circulation -> ventricular arrhythmias, weakness, paraesthesia, GI upset

(1) membrane stabilisation -> calcium gluconate
(2) shift of K+ intracellularly -> insulin/glucose, sodium bicarbonate, beta-agonists
(3) reduction of K+ load -> resonium, diuretics, dialysis

Hyperphosphataemia

• >1.45mmol/L or 25% increase
• release of intracellular PO4- due to cell lysis
• tumour cells can have up to 4x the normal levels
• tubular transport mechanisms become overloaded

-> phosphate binders
-> dialysis

Hypocalcaemia

• precipitation of calcium phosphate due to rapid increase in PO4
  -> muscle cramps, tetany, arrhythmias, seizures, renal failure from nephrocalcinosis

-> calcium gluconate only in symptomatic patients as there is a risk of precipitation with PO4-

Renal Failure

• multi-factorial
• volume depletion
• cytokine mediated reduction in renal perfusion
• ischaemic ATN
• precipitation of uric acid crystals
• calcium phosphate nephropathy

References and Links

LITFL

• ICU Mind Map — Tumour Lysis Syndrome
• Oncology Quandary 005 — Troubling Lab Strife

Journal articles and textbooks

• Cammalleri L, Malaguarnera M. Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout. Int J Med Sci. 2007 Mar 2;4(2):83-93. PMC1838823.
• McCurdy MT, Shanholtz CB. Oncologic emergencies. Crit Care Med 2012;40:2212-2222. PMID: 22584756

Social media and other web resources

• Emedicine. Tumour Lysis Syndrome
• PulmCCM.org — Cancer-Related Medical Emergencies: Tumor Lysis Syndrome