In a 50-year-old man with bulky diffuse large B-cell lymphoma who develops nausea, vomiting, oliguria, hyperkalemia, hypocalcemia and markedly elevated uric acid after the first R-CHOP cycle, which drug should be given prophylactically to prevent tumor‑lysis syndrome?

Rasburicase is the Drug to Prevent Tumor Lysis Syndrome in High-Risk DLBCL

For a patient with bulky DLBCL receiving R-CHOP, rasburicase should be administered prophylactically to prevent tumor lysis syndrome (TLS), as this patient meets high-risk criteria based on bulky disease and the presentation described represents established TLS. 1

Risk Stratification: Why This Patient is High-Risk

This patient has multiple high-risk features for TLS:

• Bulky disease (explicitly stated in the presentation) is a disease-related factor that places patients at high risk 1
• High-grade lymphoma (DLBCL) with expected rapid response to chemotherapy 1
• The clinical presentation (hyperkalemia K=6, hyperphosphatemia PO4=3, hypocalcemia Ca=1.2, markedly elevated uric acid UA=570, oliguria) represents established clinical TLS that has already occurred after the first cycle 1

Prophylactic Drug Selection Algorithm

High-Risk Patients (This Case)

Rasburicase plus hydration should be administered to all high-risk patients in an inpatient setting. 1

• Rasburicase is recommended at 0.20 mg/kg/day infused over 30 minutes 1
• The first dose should be given at least 4 hours before starting chemotherapy and continued for 3-5 days 1
• After completing rasburicase, transition to oral allopurinol 1
• Never administer allopurinol concurrently with rasburicase, as this causes xanthine accumulation and removes substrate for rasburicase 1

Low-Risk Patients (Not This Case)

Low-risk patients should receive oral allopurinol (100 mg/m² three times daily, maximum 800 mg/day) plus hydration and urine alkalinization 1

Why Rasburicase Over Allopurinol in High-Risk Patients

The mechanism of action explains the superiority:

• Rasburicase is a recombinant urate-oxidase enzyme that converts existing uric acid to allantoin, which is 5-10 times more soluble than uric acid 1, 2
• Allopurinol only blocks xanthine oxidase, preventing new uric acid formation but does not address pre-existing hyperuricemia 1
• In high-risk patients with bulky disease and rapid tumor lysis, the ability to rapidly degrade existing uric acid is critical 1, 3

Why the Other Options Are Incorrect

Thiazide Diuretics

• Thiazides are never used in TLS management
• They can worsen hyperuricemia and hypercalcemia
• No role in TLS prophylaxis

Furosemide

• Loop diuretics may be used to maintain urine output (≥100 mL/hour in adults) but only as an adjunct to hydration 1, 4
• Absolute contraindications include obstructive uropathy or hypovolemia 1, 4
• Furosemide does not prevent TLS; it only helps maintain adequate uresis after aggressive hydration is established 4
• This is a supportive measure, not prophylaxis against the metabolic derangements of TLS

Allopurinol

• Appropriate only for low-risk patients 1
• Insufficient for bulky DLBCL, which is explicitly categorized as high-risk 1
• Does not address pre-existing hyperuricemia 1

Essential Supportive Measures

Beyond rasburicase, high-risk patients require:

• Aggressive hydration starting 48 hours before chemotherapy when possible (≥2 L/m²/day) 1, 4
• Target urine output ≥100 mL/hour in adults 1, 4
• Do NOT alkalinize urine when using rasburicase, as this increases calcium phosphate precipitation risk 1, 4
• Consider steroid pre-phase (prednisone 100 mg for several days) before R-CHOP in patients with high tumor burden to reduce TLS risk 1

Critical Contraindications to Rasburicase

Rasburicase is absolutely contraindicated in: 2

• G6PD deficiency (causes severe hemolytic anemia)
• Methemoglobinemia
• Other metabolic disorders causing hemolytic anemia

These patients must receive allopurinol, hydration, and urine alkalinization instead 1

Common Pitfalls

• Never combine allopurinol with rasburicase during the active rasburicase treatment period 1
• Rasburicase causes enzymatic degradation of uric acid in blood samples at room temperature, leading to falsely low readings—samples must be immediately placed on ice 2
• The mortality rate for untreated TLS in solid tumors and lymphomas approaches 30% 3
• This patient's presentation after the first cycle indicates inadequate prophylaxis was given; future cycles require rasburicase 1