15.1 Tumor Lysis Syndrome: Cairo-Bishop Criteria, Risk Stratification, Hydration & Rasburicase
Key Takeaways
Separate the original Cairo–Bishop classification from the Howard refinements. Use an age-adjusted upper limit for the Cairo–Bishop creatinine criterion.
Assess tumor and treatment factors alongside renal function and baseline chemistry. Adjust hydration and monitoring to the risk and the child’s fluid tolerance.
Allopurinol reduces new uric acid production. Rasburicase lowers existing uric acid rapidly. Follow product and oncology guidance for each.
Screen higher-risk children before rasburicase. Known G6PD deficiency is a contraindication. Use a prechilled heparin tube, an ice-water bath and a cooled centrifuge, and analyze plasma within four hours.
Treat cardiotoxic hyperkalemia immediately. Avoid giving calcium solely for asymptomatic hypocalcemia, and involve nephrology for refractory complications.
Tumor lysis syndrome in children
Recognize the pattern and classify it
Rapid malignant cell breakdown can occur spontaneously or after antineoplastic treatment. Potassium release can cause dysrhythmias. Phosphate release can lower ionized calcium and contribute to calcium phosphate deposition in the kidney. Purine breakdown raises uric acid, which can injure the kidney. Falling kidney clearance can amplify each abnormality. Check for simultaneous threats, including infection in a febrile child with shock.
The original Cairo–Bishop classification uses at least two abnormalities from 3 days before through 7 days after treatment starts. It includes the threshold values below or a 25% increase in uric acid, potassium or phosphorus, or a 25% decrease in calcium. Clinical TLS adds a qualifying complication such as creatinine at least 1.5 times the age-adjusted upper limit of normal, a dysrhythmia or sudden death, or a seizure attributable to TLS. A patient's earlier creatinine and the laboratory upper limit answer different questions.
| Analyte | Original Cairo–Bishop concentration criterion |
|---|---|
| Uric acid | At least 8 mg/dL |
| Potassium | At least 6 mEq/L |
| Phosphorus | At least 6.5 mg/dL in children. The adult cutoff is 4.5 mg/dL. |
| Corrected total calcium | At most 7 mg/dL |
Howard refinements require two abnormalities in the same 24 hours, drop the isolated 25% rule, and account for age-specific uric acid limits in children. The corrected publication gives an ionized calcium threshold below 1.12 mmol/L. It defines AKI as a creatinine rise of at least 0.3 mg/dL, a value above 1.5 times the age-adjusted upper limit when baseline is unavailable, or average urine output below 0.5 mL/kg/h over 6 hours. It also counts symptomatic hypocalcemia as a clinical complication. Specify which system you are applying. A 25% rise in potassium from 3.6 to 4.5 mEq/L illustrates why a relative change within range may not indicate clinically important lysis. Treat an evolving emergency before the patient fulfills a scoring definition. Original Cairo–Bishop classification · Howard criteria and published ionized calcium correction
Assess risk, hydrate and monitor
Assess tumor burden, proliferation and treatment sensitivity, plus baseline uric acid, electrolytes and renal function. Bulky Burkitt lymphoma and hyperleukocytic ALL can be high risk. In the MD Anderson pediatric pathway, Burkitt lymphoma and ALL with a white count above 100,000/µL are high-risk examples. ALL with 50,000–100,000/µL is an intermediate-risk example before other modifiers. Kidney dysfunction, elevated baseline uric acid and LDH, obstruction or extensive disease can raise concern. Use the diagnosis- and regimen-specific oncology pathway for category and prophylaxis. Original risk consensus · MD Anderson pediatric pathway
Start protocol-directed IV hydration before treatment when feasible. Use the oncology protocol's fluid composition and avoid routine potassium or phosphate additives while lysis is active. Reassess based on perfusion, urine output, weight, respiratory status and electrolytes. A high-risk MD Anderson example is 2–3 L/m²/day, with a separate weight-based plan for children at or below 10 kg. For a child above 10 kg with body surface area 0.80 m², that example corresponds to 1.6–2.4 L/day, about 67–100 mL/h before individual adjustment. Pulmonary edema, oligoanuria or cardiac dysfunction can limit fluid delivery. Assess volume and obstruction before considering a loop diuretic. Avoid routine urine alkalinization because it can favor calcium phosphate precipitation. Bicarbonate given for a separate indication, such as selected severe acidemia, is a different decision.
Track potassium, phosphate, calcium, creatinine and uric acid, and monitor urine output, weights and the ECG as indicated. Use more frequent testing in active or rapidly evolving TLS. The MD Anderson pathway uses 6–8-hour labs during treatment for its high-risk group. An unstable child or one receiving emergency electrolyte therapy needs earlier reassessment. Contact nephrology early for AKI or rapidly worsening electrolyte or fluid abnormalities. MD Anderson pediatric pathway · CHOP inpatient and ICU pathway
Select and monitor urate-lowering therapy
| Agent | Action and clinical application |
|---|---|
| Allopurinol | Inhibits xanthine oxidase and reduces new uric acid production. It cannot remove uric acid already present. Use for prophylaxis when appropriate, or when rasburicase is contraindicated, with specialist input for established TLS. Consider renal function, serious cutaneous reaction risk and interactions, including with mercaptopurine or azathioprine. |
| Rasburicase | Urate oxidase converts existing uric acid to more soluble allantoin and generates hydrogen peroxide. Use in eligible high-risk children or for established hyperuricemia according to the oncology pathway. The U.S. ELITEK label specifies 0.2 mg/kg IV over 30 minutes daily for up to 5 days as one treatment course. Some centers use a single dose with laboratory-directed reassessment. That is a center protocol rather than the labeled schedule. |
A pediatric randomized trial found an 86% reduction in initial plasma uric acid after 4 hours with rasburicase versus 12% with allopurinol. This supports faster urate reduction. Continue to monitor potassium, phosphate, calcium and kidney function regardless of uric acid response.
Before rasburicase, screen higher-risk patients for G6PD deficiency, including those of African or Mediterranean ancestry. A known deficiency is a contraindication. Other label contraindications are prior anaphylaxis or severe hypersensitivity to rasburicase, and prior rasburicase-associated hemolysis or methemoglobinemia. Stop immediately and permanently for serious hypersensitivity, hemolysis or methemoglobinemia on treatment. With suspected methemoglobinemia, obtain blood co-oximetry and urgently support oxygen delivery. Known G6PD deficiency also contraindicates methylene blue. Involve toxicology and transfusion specialists for severe deterioration.
Rasburicase can degrade uric acid after sampling. Collect blood for post-dose uric acid into a prechilled heparin tube and place it immediately in an ice-water bath. Prepare plasma in a precooled 4 °C centrifuge, keep it in an ice-water bath and analyze within 4 hours of collection. An unexpectedly low result from an improperly handled specimen warrants a correctly collected repeat. ELITEK U.S. label · Pediatric randomized comparison · Allopurinol label · Methylene blue label
Treat dangerous electrolyte abnormalities and escalate
- Hyperkalemia: For cardiotoxic ECG changes, give IV calcium using the pediatric emergency protocol for membrane stabilization. This remains indicated when hypocalcemia is asymptomatic if the separate indication is cardiotoxic hyperkalemia. Use insulin with glucose and consider inhaled albuterol to shift potassium. Monitor glucose and potassium serially and arrange definitive removal for refractory or recurrent elevation. Oral binders cannot substitute for emergency stabilization or dialysis.
- Hyperphosphatemia and hypocalcemia: Stop phosphate additives and monitor ionized calcium and ECG. Consider a non-calcium phosphate binder when enteral treatment is appropriate, recognizing the limited evidence in pediatric TLS. Avoid calcium solely to normalize an asymptomatic low result. For seizures, tetany or arrhythmia from hypocalcemia, use the minimum IV calcium needed for symptoms with monitoring while addressing the phosphate burden. Calcium-phosphate product is a risk marker in some protocols. A single value cannot establish tissue deposition.
- Kidney support: Escalate for persistent or rapidly recurrent hyperkalemia, severe or refractory hyperphosphatemia with symptoms or AKI, refractory fluid overload or acidemia, or symptomatic uremia. Rapid solute generation can require early KRT. Choose intermittent or continuous support based on urgency, hemodynamics and rebound risk. Children's Mercy pediatric TLS pathway · Pediatric phosphate binder cohort · KDIGO issued AKI guideline
A 7-year-old with T-cell ALL and a white count of 185,000/µL is due to start chemotherapy tomorrow. On the same draw, uric acid is 9.2 mg/dL, phosphorus 7.4 mg/dL, potassium 5.9 mEq/L, corrected calcium 8.5 mg/dL, and creatinine 1.8 mg/dL. Prior creatinine was 0.4 mg/dL and the age-adjusted upper limit is 0.6 mg/dL. There is no alternative cause of the AKI, G6PD activity is documented normal, and there is no prior rasburicase reaction. Which classification and plan fit?
Clinical TLS before chemotherapy. Give eligible rasburicase and closely monitored hydration with urgent oncology and nephrology input.
Laboratory TLS only because the child has no seizure or arrhythmia. Observe without intervention until after chemotherapy.
No TLS because potassium is below 6 mEq/L. Add potassium to routine hydration.
No TLS can occur before chemotherapy. Start routine urine alkalinization and defer reassessment.
A 12-year-old male of Mediterranean descent with stage IV Burkitt lymphoma is scheduled to begin emergent cytoreductive chemotherapy. His baseline serum uric acid is 10.8 mg/dL, and his LDH is 4,200 U/L. Before administering rasburicase, what critical biochemical deficiency must the acute care nurse practitioner evaluate, which serious adverse reactions can occur if rasburicase is given in this condition, and what laboratory specimen precaution is mandatory?
Thiopurine methyltransferase (TPMT) deficiency; rasburicase administration triggers acute hepatic sinusoidal obstruction syndrome; uric acid blood specimens must be shielded from light and analyzed within 12 hours.
G6PD deficiency with risk of oxidative hemolysis and methemoglobinemia. For post-dose uric acid, use a prechilled heparin tube, an immediate ice-water bath, a precooled centrifuge and plasma analysis within four hours.
Direct antiglobulin (Coombs) positivity; rasburicase induces acute autoimmune thrombocytopenic purpura; blood tubes must be pre-warmed to 37°C to prevent cold agglutinin cryoprecipitation.
Creatinine clearance <30 mL/min; rasburicase undergoes primary renal elimination causing acute cortical necrosis; blood tubes must be drawn in potassium-EDTA tubes without temperature regulation.
A 5-year-old with B-ALL has active TLS during induction. Potassium is 5.1 mEq/L, phosphorus 9.8 mg/dL, ionized calcium 1.02 mmol/L and creatinine 1.4 mg/dL, up from 0.4. Urine output is 2.8 mL/kg/h, with adequate perfusion and no pulmonary edema. The ECG is normal and there is no tetany or seizure. What should the team do now?
Give IV calcium immediately to normalize ionized calcium despite the absence of symptoms or ECG changes.
Add bicarbonate to alkalinize the urine and wait for the phosphate level to fall.
Avoid IV calcium for the asymptomatic low level. Address phosphate, reassess hydration and electrolytes closely, and consult nephrology early.
Stop monitoring because adequate urine output excludes clinically important kidney injury.
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