Tumour lysis syndrome in Burkitt lymphoma: rasburicase, G6PD status and limited stock
A 24-year-old man is diagnosed with Burkitt lymphoma; staging shows a bulky abdominal mass, white cell count 45 x 10^9/L and LDH 2100 U/L (about 5 times the upper limit of normal). On admission, potassium is 5.4 mmol/L, phosphate 1.8 mmol/L, corrected calcium 2.1 mmol/L, uric acid 640 umol/L (10.8 mg/dL), creatinine 1.3 mg/dL, and urine output is 60 mL/h with no obstruction on ultrasound. The plan is to start intensive chemotherapy within 24 hours and to give rasburicase 0.2 mg/kg as a single dose plus intravenous hydration. The hospital laboratory can measure G6PD activity but the result will not be available for 24 hours. Rasburicase stock is limited to three vials and the pharmacy cannot obtain more this week. The patient comes from a region where G6PD deficiency is common in men (estimated 6-10%). He has no known previous haemolytic episodes and has never had a transfusion.
1. Classify his tumour lysis syndrome risk and justify why rasburicase is being considered rather than allopurinol. What single test must be checked before administration, and why?
Read the worked answer
High risk for tumour lysis syndrome. Criteria met: bulky abdominal Burkitt lymphoma (the highest-risk histology), LDH about 5 times the upper limit of normal, white cell count 45 x 10^9/L, and pre-treatment uric acid 640 umol/L with already raised phosphate and potassium. Burkitt lymphoma can lyse spontaneously before chemotherapy starts.
Why rasburicase rather than allopurinol: allopurinol blocks formation of new uric acid but has no effect on uric acid already present. Rasburicase is a urate oxidase that degrades circulating uric acid within hours. For high-risk disease with established hyperuricaemia (uric acid above about 450 umol/L or 8 mg/dL, or any elevation with high-risk features), guidelines recommend rasburicase; allopurinol is adequate for prophylaxis in low or intermediate risk.
Test before giving: G6PD activity. Rasburicase generates hydrogen peroxide and is absolutely contraindicated in G6PD deficiency, where it causes severe haemolysis and methaemoglobinaemia. In a man from a high-prevalence region with no prior testing, the result must be known, or the drug withheld, even though treatment is urgent. Baseline haemoglobin and methaemoglobin should also be documented.
2. Construct a management plan that is safe if G6PD status is unknown when chemotherapy starts and rasburicase supply is limited. Include drug doses, monitoring frequency and sample handling.
Read the worked answer
Because rasburicase cannot be given before G6PD status is known, and stock is limited, bridge safely and keep the option open:
- Allopurinol 300 mg orally once daily, started immediately. No renal dose reduction is needed at creatinine 1.3 mg/dL. If G6PD returns normal and uric acid is still high, switch to rasburicase 0.2 mg/kg once.
- Vigorous hydration: 2.5-3 L/m2/day IV, aiming for urine output 80-100 mL/m2/h, watching for fluid overload.
- Do not alkalinise the urine routinely - it does not improve outcomes and promotes calcium phosphate deposition.
- Monitor every 6-8 hours: potassium, phosphate, calcium, creatinine, uric acid, LDH and urine output. Treat hyperkalaemia, use phosphate binders for hyperphosphataemia, and treat hypocalcaemia only if symptomatic.
- Uric acid sample handling if rasburicase is given: collect in a pre-chilled tube and transport on ice; otherwise the drug continues to degrade uric acid ex vivo and gives a falsely low result.
- Reserve the three vials for the highest-risk moment (for example uric acid above 600 umol/L despite allopurinol, or falling renal function) rather than using them prophylactically in a patient of unknown G6PD status.
3. If G6PD deficiency is later confirmed and uric acid rises to 800 umol/L despite allopurinol, what are the options and the risks?
Read the worked answer
If G6PD deficiency is confirmed, rasburicase is permanently contraindicated - do not give it even at a reduced dose; haemolysis can be fatal.
Options:
- Continue allopurinol, or switch to febuxostat 80 mg daily (not dependent on the same pathway, though evidence in tumour lysis syndrome is limited and G6PD caution still applies).
- Intensify hydration and correct electrolytes.
- Renal replacement therapy is the definitive option for refractory hyperuricaemia with oliguria or worsening renal function; it clears uric acid and phosphate and corrects potassium.
- Monitor haemoglobin, reticulocytes, bilirubin and methaemoglobin; avoid other oxidant drugs such as dapsone, nitrofurantoin, primaquine and high-dose sulfonamides.
- Recheck uric acid every 6 hours; the target is a falling trend with stable renal function, not a single normal value.
Risks to discuss with the team: allopurinol will not lower the existing uric acid load quickly, so the patient may need dialysis; and any delay in chemotherapy to await the G6PD result must be weighed against the risk of spontaneous lysis in bulky Burkitt lymphoma. In practice the allopurinol-plus-hydration bridge, with dialysis available, is the pragmatic answer.