Overview
Definition:
Tumor Lysis Syndrome (TLS) is a life-threatening condition characterized by the rapid release of intracellular contents into the bloodstream due to the breakdown of malignant cells
This typically occurs spontaneously or, more commonly, following initiation of cytotoxic therapy for rapidly growing tumors, particularly hematologic malignancies like acute lymphoblastic leukemia (ALL) and Burkitt lymphoma
The massive release of intracellular ions and macromolecules leads to metabolic derangements, primarily hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia, which can result in acute kidney injury (AKI), cardiac arrhythmias, and seizures.
Epidemiology:
TLS is a significant complication in pediatric hematologic malignancies
Its incidence varies based on the specific malignancy, tumor burden, and treatment regimen
High-risk malignancies include Burkitt lymphoma, acute lymphoblastic leukemia (ALL), and T-cell acute lymphoblastic leukemia (T-ALL)
Patients with large tumor volumes, high white blood cell counts (WBC), and pre-existing renal impairment are at increased risk
Spontaneous TLS can occur in up to 20% of patients with Burkitt lymphoma, while chemotherapy-induced TLS is even more common, especially with intensive regimens.
Clinical Significance:
Tumor Lysis Syndrome is a medical emergency that requires prompt recognition and aggressive management to prevent severe morbidity and mortality
Untreated TLS can lead to irreversible kidney damage, life-threatening cardiac dysrhythmias, neurological complications, and death
Therefore, proactive prevention strategies are paramount for all patients initiating therapy for high-risk hematologic malignancies
Understanding the risk factors, monitoring parameters, and therapeutic interventions is crucial for pediatric residents preparing for DNB and NEET SS examinations and for providing optimal patient care.
Risk Stratification
Risk Factors:
High tumor burden
High WBC count (>50 x 10^9/L for ALL/lymphoma)
Rapidly proliferating tumors (Burkitt lymphoma, T-ALL)
Pre-existing renal insufficiency
Dehydration
Acidosis
Elevated LDH levels
Certain chemotherapy agents.
High Risk Conditions:
Burkitt lymphoma
T-cell acute lymphoblastic leukemia (T-ALL)
High-grade B-cell lymphoma
Patients with bulky disease and high WBC counts (>100 x 10^9/L) regardless of histology.
Intermediate Risk Conditions:
Standard acute lymphoblastic leukemia (ALL)
Diffuse large B-cell lymphoma
Patients with high WBC counts (<50 x 10^9/L) and moderate tumor burden.
Low Risk Conditions:
Other less aggressive lymphomas
Patients with low WBC counts and minimal tumor burden.
Prevention Strategies
Hydration:
Aggressive intravenous fluid hydration is the cornerstone of TLS prevention
Aim for a urine output of at least 2-3 mL/kg/hour using isotonic crystalloid solutions (e.g., 0.9% saline)
Fluid administration should commence at least 24-48 hours prior to chemotherapy and continue throughout treatment
Monitor fluid balance closely to avoid fluid overload, especially in patients with cardiac dysfunction.
Alkalinization:
Urine alkalinization with sodium bicarbonate can be considered to increase the solubility of uric acid, reducing the risk of urate nephropathy
However, this is controversial and should be used cautiously as it can exacerbate hyperphosphatemia and lead to calcium phosphate precipitation
The goal is a urine pH of 7.0-7.5
This is less effective for preventing xanthine or other metabolite precipitation.
Allopurinol:
Allopurinol is a xanthine oxidase inhibitor that reduces uric acid production by blocking the conversion of hypoxanthine and xanthine to uric acid
It is generally recommended for all patients at intermediate or high risk of TLS
The typical pediatric dose is 10 mg/kg/day orally, divided every 12-24 hours, starting 24-48 hours before chemotherapy.
Rasburicase:
Rasburicase (urate oxidase) is a recombinant enzyme that catalyzes the degradation of uric acid to allantoin, a highly water-soluble compound that is readily excreted by the kidneys
It is indicated for patients at very high risk of TLS, especially those with established hyperuricemia or renal dysfunction, or when allopurinol is insufficient
It provides a rapid and potent reduction in uric acid levels
The standard dose is 0.2 mg/kg once daily IV for up to 5 days
Contraindicated in G6PD deficiency
Monitor for hypersensitivity reactions.
Monitoring:
Close monitoring of serum electrolytes (potassium, phosphate, calcium, uric acid), renal function (BUN, creatinine), and urine output is essential
Daily or more frequent monitoring is required during the initial days of chemotherapy
Electrocardiogram (ECG) monitoring is crucial to detect arrhythmias associated with hyperkalemia.
Clinical Presentation And Monitoring
Laboratory Abnormalities:
Hyperkalemia (>5.5 mmol/L)
Hyperphosphatemia (>4.5 mg/dL in children)
Hypocalcemia (<7.0 mg/dL)
Hyperuricemia (>7.5 mg/dL)
Elevated LDH
Elevated BUN and creatinine.
Clinical Manifestations:
Neurological: Lethargy, weakness, seizures, altered mental status
Cardiovascular: Palpitations, arrhythmias, hypotension, cardiac arrest
Renal: Decreased urine output, oliguria, anuria, flank pain
Gastrointestinal: Nausea, vomiting, abdominal pain.
Monitoring Schedule:
Daily serum electrolytes, BUN, creatinine, and uric acid are essential
Urine output should be measured hourly
ECG monitoring is indicated for significant electrolyte abnormalities
In high-risk patients, baseline and daily monitoring of calcium, phosphate, and uric acid are critical
More frequent monitoring may be required during the first 72 hours post-chemotherapy.
Signs Of Acute Kidney Injury:
Decreased urine output
Elevated serum creatinine and BUN
Fluid overload (edema, pulmonary congestion)
Electrolyte imbalances that may persist despite correction attempts.
Management Of Established Tls
Initial Management:
Immediate cessation of chemotherapy if ongoing
Aggressive IV fluid resuscitation to maintain adequate urine output
Correction of hyperkalemia and hypocalcemia
Treatment of hyperphosphatemia.
Hyperkalemia Management:
Intravenous calcium gluconate to stabilize cardiac membranes
Insulin and glucose infusion to shift potassium intracellularly
Sodium bicarbonate for severe acidosis
Diuretics (furosemide) if renal function is adequate
Potassium binders (e.g., patiromer, sodium polystyrene sulfonate)
Hemodialysis for severe, refractory hyperkalemia or renal failure.
Hypocalcemia Management:
Intravenous calcium gluconate is indicated only if symptomatic or with significant ECG changes
Avoid rapid infusion, which can cause rebound hyperkalemia
Monitor ionized calcium levels.
Hyperphosphatemia Management:
Phosphate binders (e.g., calcium acetate, sevelamer) should be initiated orally or via nasogastric tube
Avoid calcium-containing phosphate binders if hypercalcemic
Hydration and diuretics may help promote phosphate excretion
Dialysis may be necessary for severe, refractory hyperphosphatemia.
Uric Acid Management:
If established hyperuricemia and renal involvement, rasburicase is the treatment of choice
Allopurinol is less effective in established TLS
Hydration is paramount
If hyperuricemia is severe and causing AKI, hemodialysis may be necessary.
Prognosis And Follow Up
Factors Affecting Prognosis:
Timeliness of diagnosis and initiation of management
Severity of metabolic derangements
Development of acute kidney injury
Underlying malignancy and its response to therapy
Comorbidities.
Outcomes:
With prompt and appropriate management, TLS is usually reversible
However, severe cases can lead to irreversible renal damage, cardiac complications, and death
Early identification and aggressive preventive measures significantly improve outcomes.
Follow Up:
Patients who have experienced TLS require close monitoring of renal function and electrolyte balance for several weeks
Long-term follow-up should include assessment for chronic kidney disease
Education of parents and caregivers regarding signs and symptoms of recurrence is vital.
Key Points
Exam Focus:
Identify high-risk pediatric malignancies for TLS
Understand the primary metabolic derangements and their immediate clinical consequences
Know the key preventive agents: hydration, allopurinol, rasburicase, and their indications/contraindications
Recognize the management steps for established TLS, especially hyperkalemia and hypocalcemia.
Clinical Pearls:
Always start aggressive hydration and consider allopurinol or rasburicase *before* chemotherapy in high-risk patients
Monitor electrolytes and renal function *very* closely during the first 72 hours after initiating therapy
Rasburicase is a powerful tool for rapid uric acid reduction but carries a risk of anaphylaxis and hemolytic anemia
screen for G6PD deficiency
Hypocalcemia is a consequence, not a cause, of hyperphosphatemia
treat the phosphate overload first.
Common Mistakes:
Delaying preventive measures until after chemotherapy has started
Inadequate fluid resuscitation
Over-reliance on allopurinol in very high-risk patients
Incorrect dosing or administration of rasburicase
Aggressive correction of hypocalcemia without addressing hyperphosphatemia
Failing to monitor ECG for hyperkalemia-related arrhythmias.