What is the recommended monitoring protocol for tumor‑lysis syndrome in children with acute lymphoblastic leukaemia receiving induction chemotherapy?

Tumor Lysis Syndrome Monitoring in Pediatric Acute Lymphoblastic Leukemia

Pediatric patients at high risk for tumor lysis syndrome should have laboratory parameters monitored every 4 to 6 hours after initiating chemotherapy, measuring uric acid, phosphate, potassium, creatinine, calcium, and LDH, along with strict fluid input and urine output tracking. 1

Risk Stratification Before Monitoring

Children with ALL are at high risk for TLS when they present with:

• White blood cell count ≥50,000/mm³ (associated with 2.6-fold increased TLS risk) 2
• T-cell ALL subtype (4.7-fold increased risk compared to B-ALL) 2
• Age <6 months with any WBC or age <3 months regardless of count 1
• LDH >2× upper limit of normal 3
• Pre-existing renal impairment, dehydration, or obstructive uropathy 1, 3

The incidence of TLS increases dramatically with higher WBC counts: 26% when WBC <100,000/mm³, 50% when WBC 100,000-200,000/mm³, and approaches 100% when WBC >300,000/mm³ 4.

Specific Laboratory Monitoring Protocol

Initial Monitoring Window (First 24 Hours)

For high-risk patients, measure the following parameters every 4 to 6 hours after the first chemotherapy dose: 1

• Uric acid – Target <8 mg/dL (476 μmol/L); if rasburicase is administered, recheck 4 hours post-dose, then every 6-8 hours 1
• Potassium – Verify elevated values immediately with a second sample to exclude pseudohyperkalemia from hemolysis during phlebotomy 1
• Phosphate – Hyperphosphatemia occurs in 80% of hyperleukocytic ALL cases 4
• Calcium – Hypocalcemia develops in 26% of cases and is more severe with hyperleukocytosis 4, 2
• Creatinine and BUN – Rising creatinine indicates clinical TLS and requires immediate nephrology consultation 1, 3
• LDH – Continue monitoring until normalization, which signals TLS resolution 1

Extended Monitoring (Beyond 24 Hours)

After the first 24 hours, continue monitoring every 12 hours for the next 3 days, then daily until all parameters normalize. 3 If TLS has not occurred within 48 hours of chemotherapy completion, the likelihood of developing TLS becomes essentially zero 1.

Critical Sample Handling

Blood samples for uric acid measurement must be placed immediately on ice to prevent ex vivo enzymatic degradation by rasburicase, which falsely lowers measured levels 3, 5. This is a common pitfall that can mask persistent hyperuricemia.

Clinical Monitoring Parameters

Beyond laboratory values, track these clinical indicators every 4-6 hours: 1

• Fluid input – Target 2-3 L/m²/day IV hydration 3
• Urine output – Maintain ≥80-100 mL/m²/hour in children (or 3-4 mL/kg/hour for children <10 kg) 3, 5
• Urine specific gravity – Keep at approximately 1.010 5
• Cardiac monitoring – Continuous ECG for patients with potassium >6 mEq/L to detect QRS widening 1

Facility Requirements for High-Risk Patients

Chemotherapy should only be administered in facilities with immediate access to dialysis and intensive care units. 1 Notify nephrology in advance for all high-risk patients, as 1.5% of pediatric patients still require dialysis despite rasburicase availability 1.

Common Monitoring Pitfalls to Avoid

• Failing to verify hyperkalemia – Always obtain a second sample before aggressive intervention, as hemolysis during blood draw causes fictitious elevation 1
• Inadequate monitoring frequency – Checking labs only every 12-24 hours in high-risk patients misses the rapid metabolic changes that occur in the first 6 hours 1, 3
• Ignoring fluid balance – TLS parameters worsen rapidly when urine output falls below target; loop diuretics may be needed to maintain output 3, 5
• Premature discontinuation – Continue monitoring until LDH normalizes, not just until electrolytes stabilize 1

Special Considerations for Hyperleukocytosis

In children presenting with WBC >100,000/mm³, hyperphosphatemia and hypocalcemia are significantly more severe (2.6-fold and 5.4-fold increased odds, respectively) 2. These patients require the most intensive monitoring schedule and should be considered for L-asparaginase administration, which reduces WBC count by 42% at 24 hours and 76% at 48 hours, effectively preventing TLS 6.