18.2 Tumor Lysis Syndrome

CPHON TCO V.C.3 is tumor lysis syndrome (TLS): the metabolic crash when a large mass of cancer cells dies at once and dumps intracellular contents into blood. It is a preventable emergency if hydration and uric-acid control start before or with the first cytoreductive doses, and it is a dialysis emergency if potassium and the kidney get ahead of you.

Who is at risk

Highest pediatric risk is high-burden acute lymphoblastic leukemia (ALL), Burkitt lymphoma, and other high-grade non-Hodgkin lymphomas (NHL) with bulky nodes or a large abdomen. Acute myeloid leukemia (AML) can cause TLS, especially with a high white-cell count, but Burkitt and T-ALL or B-ALL with a packed marrow or mediastinum are the classic CPHON pictures. Spontaneous TLS can start before chemotherapy when cells are already turning over. Induction steroids, hydroxyurea, the first chemotherapy block, and even the fall in uric acid after rasburicase as remaining cells lyse can accelerate the dump.

A 6-year-old with a rock-hard abdomen from Burkitt lymphoma, uric acid already high, lactate dehydrogenase (LDH) sky-high, and a white-cell count in the six figures is a TLS admission before the first vincristine or cyclophosphamide bag. A “well-looking” preschooler with newly diagnosed ALL and a potassium of 5.8 mEq/L on the diagnostic chemistry panel is not “fine to wait until Monday.” Risk climbs with high LDH, high baseline uric acid, bulky disease, preexisting dehydration or renal impairment, acidic urine, and oliguria. The nurse does not need a research-score calculator to start precautions; the diagnosis plus a high burden is enough to open the TLS order set.

The laboratory four and the kidney

Dying cells release potassium, phosphate, and purines that become uric acid. Phosphate binds calcium, so secondary hypocalcemia follows hyperphosphatemia. Uric acid precipitates in renal tubules; the calcium-phosphate product can do the same. The organ that fails is the kidney: oliguria, rising creatinine, and then a potassium that no longer has an exit.

Remember the direction, not a trivia museum:

• Hyperkalemia — arrhythmia, peaked T waves, widened QRS, sine-wave risk.
• Hyperphosphatemia
• Hypocalcemia (secondary) — tetany, Chvostek or Trousseau signs in older children, seizures, prolonged QT, arrhythmia.
• Hyperuricemia
• Acute kidney injury (AKI)

Cairo-Bishop is a widely used laboratory versus clinical TLS framework in oncology (two or more laboratory shifts in a defined peri-therapy window for laboratory TLS; clinical TLS adds creatinine rise, arrhythmia, seizure, or death). You may name that framework. Do not treat every numeric cutoff as if ONCC published it. CPHON items test whether you recognize the pattern and act, not whether you can recite an adult paper’s milligram-per-deciliter table from memory.

Prevention: water first, then the uric-acid drug

Hydration is the intervention that actually protects tubules. Typical pediatric orders run two to four times maintenance (often about 2–3 L/m²/day on cooperative-group pathways) with no potassium in the initial fluids. Adding potassium to “make the bag complete” is how you help a lysing child fibrillate. Alkalinization of urine was used historically with allopurinol to keep uric acid soluble; many contemporary rasburicase-based pathways omit routine bicarbonate because alkaline urine can worsen calcium-phosphate precipitation. Follow the protocol in front of you; do not invent bicarbonate as a CPHON default.

Two uric-acid strategies, different jobs:

• Allopurinol inhibits xanthine oxidase so the child makes less new uric acid. It does not destroy uric acid already in plasma. It is prevention and slower control.
• Rasburicase is recombinant urate oxidase. It converts existing uric acid to allantoin, which is far more soluble, and the uric acid falls within hours. It is the drug for established hyperuricemia and for the highest-burden Burkitt and ALL pictures.

Rasburicase is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficiency because the hydrogen peroxide generated can cause hemolysis and methemoglobinemia. Screen when time allows, especially in populations with higher G6PD prevalence, and never give rasburicase to a child with known G6PD deficiency. After rasburicase, uric acid samples must be placed on ice and assayed immediately; the enzyme keeps working in a warm tube and produces a falsely low uric acid. Treating a “normal” room-temperature uric acid after rasburicase as proof that TLS has resolved is a lab-handling error.

Hyperkalemia, calcium, and dialysis

Put the child on telemetry once TLS is in play or potassium is rising. Stop potassium in fluids, diet, and additives. Protocol potassium treatments, used as ordered:

• Sodium polystyrene sulfonate (kayexalate) binds potassium in the gut—slower, not a code drug.
• Insulin plus glucose drives potassium intracellularly—faster temporizing.
• Calcium (gluconate or chloride per setting) protects the myocardium when electrocardiogram (ECG) changes are present; it does not lower serum potassium.
• Beta-agonists and loop diuretics appear on some pathways if the child still makes urine and can tolerate volume shifts.
• Dialysis for refractory hyperkalemia, volume overload, uremia, or a calcium-phosphate crisis the kidney cannot clear.

Hypocalcemia: treat tetany, seizures, and arrhythmia. If phosphate is still extremely high and the child is asymptomatic, many teams hold aggressive calcium replacement to avoid precipitating more calcium-phosphate in tissues and kidneys. That caution is the CPHON trap. A child with a calcium of 6.2 mg/dL who is seizing still gets calcium; a quiet child with the same number and a phosphate of 12 mg/dL is a nephrology conversation, not a reflex calcium-gluconate race.

A 6-year-old Burkitt patient on hour 8 of induction who develops peaked T waves, oliguria, phosphate 11 mg/dL, calcium 6.4 mg/dL, and uric acid falling after rasburicase is still a TLS emergency: telemetry, insulin-glucose and cardioprotective calcium as ordered, hold extra calcium once tetany is absent if phosphate remains extreme, and call for dialysis rather than stacking oral binders at the bedside while the QRS widens. A 15-year-old with T-ALL and a mediastinal mass needs the same chemistry clock even if the airway crisis stole the first hour of attention.

That is TCO V.C.3: name high-burden ALL, Burkitt, and NHL, watch the four labs plus the kidney, hydrate without potassium, choose allopurinol versus rasburicase with the G6PD and ice-tube rules, and treat potassium and symptomatic hypocalcemia as cardiac emergencies.