At risk of tumour lysis syndrome (TLS)
Starting cancer therapy (chemotherapy, targeted, immune or radiotherapy), or TLS present before therapy.
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Hematology & OncologyEmergency
Tumor Lysis Syndrome (TLS) Prevention & Management
Tumor Lysis Syndrome (TLS) Prevention & Management: At risk of tumour lysis syndrome (TLS) → Child, or venetoclax: use the specific TLS protocol → Class...
Pathway Overview
19 steps
Algorithm Steps
19 total
01Start 02Warning Child, or venetoclax: use the specific TLS protocol
Drug doses in this pathway are for adults. The rasburicase 0.2 mg/kg dose also applies to children.
- Child: use the paediatric oncology TLS protocol
- Venetoclax ramp-up (CLL or AML): use the venetoclax TLS protocol; risk depends on node size and lymphocyte count
- Other new targeted or cell therapies: check the drug-specific TLS advice
03Action Classify TLS risk before therapy
Use cancer type, WCC, LDH, bulk (10 cm or more) and kidney function. Reassess before each new treatment.
- High: Burkitt or lymphoblastic lymphoma stage III-IV or LDH 2 x ULN or more; ALL with WCC above 100 x 10^9/L or LDH 2 x ULN or more; AML with WCC above 100 x 10^9/L; high-grade NHL (e.g. DLBCL) with LDH above ULN and bulky disease
- Intermediate: AML with WCC 25-100 x 10^9/L or LDH 2 x ULN or more; ALL with WCC below 100 x 10^9/L and LDH below 2 x ULN; stage I-II Burkitt or lymphoblastic lymphoma with LDH below 2 x ULN; high-grade NHL with LDH above ULN, not bulky; CLL on monoclonal antibodies; fast-responding solid tumours (neuroblastoma, germ cell, small-cell lung)
- Low: most solid tumours, myeloma, CML, indolent NHL, Hodgkin lymphoma, CLL on alkylating agents or BTK inhibitors, AML with WCC below 25 x 10^9/L and LDH below 2 x ULN, high-grade NHL with normal LDH
- Move up one level: low risk with kidney dysfunction or renal involvement (not myeloma); intermediate risk with kidney dysfunction, renal involvement, or uric acid, K+ or phosphate above ULN
04Action Start prophylaxis by risk level
Start 24-48 h before cancer therapy. High risk: consider delaying therapy until prophylaxis has started; if it cannot wait, treat in ICU or a haematology unit.
- High risk: IV hydration plus rasburicase (if G6PD normal); frequent monitoring
- Intermediate risk: IV hydration plus allopurinol; rasburicase if kidney impairment, cannot take high fluid volumes, or allopurinol not tolerated
- Low risk: monitoring and normal hydration; add allopurinol if bulky or advanced disease, high proliferation or early metabolic changes
- Uric acid above 0.45 mmol/L, or TLS already present before therapy: rasburicase preferred (if G6PD normal)
05Action Intermediate or high risk: IV hydration
Heart failure, oliguria or AKI: high fluid volumes can cause fluid overload; set the volume with nephrology or ICU.
- IV fluid 3 L/m2/day unless contraindicated
- Target urine output 100 mL/m2/h or more
- No K+, calcium or phosphate in the fluids at first
- Weigh twice daily; strict fluid balance chart
- Diuretic only if needed to keep urine output; not if hypovolaemic or urinary obstruction
- No urinary alkalinisation; IV sodium bicarbonate only for metabolic acidosis
06Warning Before rasburicase: test G6PD. Deficient: do not give
Rasburicase in G6PD deficiency causes haemolysis and methaemoglobinaemia. Also contraindicated after hypersensitivity to rasburicase or other uricases.
- Test G6PD before the first dose
- G6PD deficient: no rasburicase. Use hydration and allopurinol; get haematology advice
- Result not back and rasburicase is urgent: senior haematologist decides
07Action G6PD normal and rasburicase indicated: rasburicase
Indicated: high risk, uric acid above 0.45 mmol/L, TLS present, or intermediate risk as in the step above. Do not give allopurinol with rasburicase.
- Rasburicase 0.2 mg/kg IV once daily over 30 min in 50 mL sodium chloride 0.9%, for up to 5-7 days (adult and child; the PI sets no maximum dose)
- Adult alternative: one fixed dose, 6 mg IV (high risk) or 3 mg IV (intermediate risk); repeat only if uric acid stays high
- Round weight-based doses to the nearest 1.5 mg vial
- Uric acid samples: pre-chilled heparin tube in an ice-water bath, test within 4 h (else falsely low)
- Watch for anaphylaxis, haemolysis and methaemoglobinaemia
08Action Intermediate risk, or no rasburicase: allopurinol
Mercaptopurine or azathioprine: avoid; if needed, cut the thiopurine dose to one quarter. Kidney impairment: reduce allopurinol by 50% or more. Check interactions with cyclophosphamide and high-dose methotrexate.
- Adult: allopurinol 100 mg/m2 orally every 8 h (max 800 mg/day); 300 mg daily is common practice
- Start 24-48 h before therapy; continue 3-7 days after it ends, or until uric acid and LDH are normal
- Does not lower uric acid that is already high: uric acid high or rising, change to rasburicase (if G6PD normal)
- HLA-B*58:01 carriers (common in Han Chinese, Thai, Korean): high risk of SJS/TEN; consider testing first
- Allopurinol allergy: hydration with close monitoring; consider rasburicase
09Action Monitor for TLS through the risk period
TLS is most common 12-72 h after therapy starts. Keep monitoring for the whole risk period of the regimen.
- K+, phosphate, calcium, uric acid, creatinine, LDH; urine output and fluid balance
- High risk: labs every 4-6 h after therapy starts; continuous cardiac monitoring
- Intermediate risk: labs every 8-12 h
- Low risk: labs daily
10Decision TLS, or one dangerous abnormality?
Laboratory TLS: 2 or more of these in the same 24 h, from 3 days before to 7 days after therapy starts. Clinical TLS adds creatinine 1.5 x ULN or more, arrhythmia or seizure. Answer Yes also for one abnormality alone: K+ 6.0 mmol/L or more, AKI or oliguria, arrhythmia, seizure or symptomatic low calcium.
- Uric acid 0.476 mmol/L or more, or a 25% rise from baseline
- K+ 6.0 mmol/L or more, or a 25% rise
- Phosphate 1.45 mmol/L or more (child 2.1 mmol/L), or a 25% rise
- Corrected calcium 1.75 mmol/L or less, or a 25% fall
- If Yes
11Action TLS or dangerous abnormality: escalate now
Senior haematology review now. Call nephrology early. Clinical TLS or rising K+: ICU, HDU or haematology unit with cardiac monitoring.
- Continuous cardiac monitoring; K+, phosphate, calcium, uric acid and creatinine every 4-6 h, sooner if K+ high
- Urine output hourly; strict fluid balance
- Stop K+ and phosphate intake; review nephrotoxic drugs
- Treat each abnormality in the next steps; several may need treatment at the same time
12Action K+ 6.0 mmol/L or more or ECG changes: treat hyperkalaemia
K+ can rise fast in TLS: call the renal or ICU team early. Give IV calcium for ECG changes even if phosphate is high or the patient takes digoxin.
- ECG changes: calcium gluconate 10% 30 mL IV over 10 min; repeat if changes persist
- Insulin (soluble) 10 units with glucose 25 g (50 mL of 50%) IV; glucose below 7.0 mmol/L before: then glucose 10% 50 mL/h for 5 h; check glucose for 6 h
- K+ 6.5 mmol/L or more: add salbutamol 10-20 mg nebulised (never alone; heart disease: lower dose with cardiac monitoring)
- Sodium zirconium cyclosilicate 10 g orally three times daily, up to 72 h
- K+ rising or not controlled, mainly with oliguria: dialysis
13Action Phosphate high: limit intake, give a binder
High phosphate is hard to correct and lowers calcium. Severe or rising phosphate with AKI or low calcium: dialysis.
- Stop phosphate in food, fluids and drugs
- Oral phosphate binder with meals (for example sevelamer); evidence in TLS is limited
- Do not give calcium to treat high phosphate or low calcium without symptoms
14Action Low calcium with symptoms: IV calcium, lowest dose
Symptoms: tetany, seizures, arrhythmia, long QT. No symptoms: do not treat; extra calcium increases calcium-phosphate precipitation.
- Adult: calcium gluconate 10% 10-20 mL in 50-100 mL glucose 5% IV over 10 min with ECG monitoring
- Give the lowest dose that stops symptoms; repeat only if symptoms return
- Symptomatic low calcium from high phosphate: consider dialysis
- On digoxin: continuous ECG monitoring during IV calcium
15Action Uric acid high or AKI: rasburicase if G6PD normal
Give rasburicase when TLS develops, also after allopurinol, unless contraindicated. G6PD deficient: no rasburicase.
- Rasburicase dose as in the prophylaxis step; stop allopurinol
- Continue IV fluids unless oliguric or fluid overloaded
- Low urine output after good hydration: loop diuretic (e.g. furosemide); not if hypovolaemic or urinary obstruction
- No urinary alkalinisation
16Decision Dialysis needed?
Use lower thresholds than in other AKI, because K+ can rise fast in TLS. Decide with nephrology.
- K+ high and not controlled by medical treatment
- Oliguria, anuria or fluid overload not responding to treatment
- Severe or rising phosphate, or symptomatic low calcium from high phosphate
- Severe metabolic acidosis or uraemic complications
- If Yes
17Action Dialysis needed: start renal replacement therapy
With nephrology and ICU.
- Continuous therapy (CVVH, CVVHD or CVVHDF) removes more phosphate; preferred if unstable
- Intermittent haemodialysis if stable; removes K+ fast
- K+ and phosphate can rise again after a session: recheck often
- Allopurinol is removed by dialysis: dose after each session
18Action Continue monitoring until the risk period ends
No TLS: keep the schedule for the risk level. After TLS: labs every 4-6 h until stable. Any new abnormality: go back to the TLS check and treat.
- One abnormal value only: uric acid high or rising, give rasburicase (if G6PD normal); phosphate high, stop phosphate intake and recheck sooner
- Keep IV fluids for urine output 100 mL/m2/h or more, unless oliguric or fluid overloaded
- Allopurinol: continue 3-7 days after therapy ends, or until uric acid and LDH are normal
- Restart or continue cancer therapy only after the treating team reviews TLS
- Reassess TLS risk before each new cycle or new drug
19Outcome Risk period over, labs stable: continue cancer care
K+, phosphate, calcium, uric acid and creatinine stable, and urine output normal.
If No- Path rejoins step 18Shared downstream outcome
If No- Path rejoins step 18Shared downstream outcome
Guideline Source
eviQ (Cancer Institute NSW) Prevention of tumour lysis syndrome, ID 108 v6 (2025); risk model from Cairo et al., Br J Haematol 2010
Clinical Safety Information
Clinical Decision Support — Not a Substitute for Clinical Judgment
Individual patient factors may require deviation from these recommendations.
Known Limitations
- Drug doses are for adults (rasburicase dose applies to adults and children); children: use the paediatric oncology TLS protocol
- CLL on venetoclax and other new targeted agents: use the drug-specific TLS protocol
- Dialysis thresholds vary by unit; decide with nephrology
- Does not cover changes to specific chemotherapy regimens
Contraindicated Populations
G6PD_deficiency_for_rasburicasehypersensitivity to rasburicase or other uricases (rasburicase)mercaptopurine or azathioprine at full dose with allopurinol (avoid; if needed, cut the thiopurine dose to one quarter)
Applicable Regions
AUNZUKEUUS
AU: eviQ ID 108 is the Australian reference. Rasburicase (Fasturtec), allopurinol (Zyloprim), sodium zirconium cyclosilicate (Lokelma) and sodium polystyrene sulfonate (Resonium A) are on the ARTG. Lab units are mmol/L.
UK: BSH 2015 TLS guideline (Jones et al.) gives similar risk-based prophylaxis.
US: Rasburicase is sold as Elitek. Uric acid 0.476 mmol/L = 8 mg/dL; phosphate 1.45 mmol/L = 4.5 mg/dL; corrected calcium 1.75 mmol/L = 7 mg/dL; K+ mmol/L = mEq/L.
Version 2Next review: 2027-09-30
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Frequently Asked Questions
What is the Tumor Lysis Syndrome (TLS) Prevention & Management?
The Tumor Lysis Syndrome (TLS) Prevention & Management is a emergency clinical algorithm for Hematology & Oncology. It provides a structured decision tree to guide clinical decision-making, based on eviQ (Cancer Institute NSW) Prevention of tumour lysis syndrome, ID 108 v6 (2025); risk model from Cairo et al., Br J Haematol 2010.
What guideline is the Tumor Lysis Syndrome (TLS) Prevention & Management based on?
This algorithm is based on eviQ (Cancer Institute NSW) Prevention of tumour lysis syndrome, ID 108 v6 (2025); risk model from Cairo et al., Br J Haematol 2010.
What are the limitations of the Tumor Lysis Syndrome (TLS) Prevention & Management?
Known limitations include: Drug doses are for adults (rasburicase dose applies to adults and children); children: use the paediatric oncology TLS protocol; CLL on venetoclax and other new targeted agents: use the drug-specific TLS protocol; Dialysis thresholds vary by unit; decide with nephrology; Does not cover changes to specific chemotherapy regimens. Individual patient factors may require deviation from these recommendations.
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