# Student Handout: Tumor Lysis Syndrome

> **Learning objective:** Recognize tumor lysis syndrome (TLS) as an oncologic emergency, apply Cairo-Bishop risk stratification, implement prevention protocols, and manage each metabolic derangement

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## What is Tumor Lysis Syndrome?

**Definition:** Syndrome of severe metabolic derangements resulting from massive, rapid release of intracellular contents when malignant cells die. It can follow chemotherapy or targeted therapy, and can also occur spontaneously before treatment; risk depends on tumor, treatment, and patient factors.

**Why it matters:** TLS is **life-threatening** if not recognized and managed promptly. Hyperkalemia can cause fatal arrhythmias; hyperphosphatemia causes secondary hypocalcemia → tetany, seizures, cardiac dysfunction.

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## Epidemiology & Risk

### Who Is at High Risk?

**Tumor context:** Acute leukemias and aggressive lymphomas can carry substantial risk, especially with high cell count, bulk or treatment sensitivity. Some bulky, rapidly responding solid tumors can also cause TLS. A cancer label alone does not assign every patient to the same risk category.

**High-risk patient factors:** - Large tumor burden / High LDH (\>1,500 IU/L indicates high cell turnover) - Rapidly proliferating disease - Pre-existing renal impairment (↓ ability to excrete K+, urate, phosphate) - Dehydration - Acidosis (↑ extracellular K+)

### Timing

- **Peak risk:** 12–48 hours after start of chemotherapy
- **Can occur:** Up to 7 days post-initiation
- **Rapid onset:** Metabolic derangements develop quickly; clinical deterioration can be fulminant

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## Cairo-Bishop Diagnostic Criteria (2004)

TLS is classified as **Laboratory TLS** or **Clinical TLS** based on objective lab parameters:

### Laboratory TLS (≥2 of the following):

| Parameter | Criterion |
|----|----|
| **Uric acid** | ≥8.0 mg/dL (or 25% ↑ from baseline) |
| **Potassium** | ≥6.0 mEq/L (or 25% ↑ from baseline) |
| **Phosphate** | ≥4.5 mg/dL in adults or ≥6.5 mg/dL in children (or 25%↑from baseline in the original definition) |
| **Calcium** | ≤7.0 mg/dL (corrected) (or 25% ↓ from baseline) |

**Note:** Calcium is one of the four laboratory criteria even though hypocalcemia is often secondary to phosphate release. The original Cairo–Bishop window is 3 days before to 7 days after treatment. Interpret concurrent abnormalities clinically; a 25% change alone may be unimportant when the value remains normal.

### Clinical TLS (≥1 of the following):

| Finding | Details |
|----|----|
| **Seizures** | Secondary to hypocalcemia, hypomagnesemia, or osmotic shifts |
| **Arrhythmias** | From severe hyperkalemia, hypocalcemia, QT prolongation |
| **Cardiac arrest** | Sudden death from electrolyte derangements |
| **AKI** | Original Cairo–Bishop clinical criterion uses creatinine≥1.5 times the age-adjusted upper limit of normal; also assess dynamic AKI by modern creatinine/urine-output criteria. AKI may have multiple mechanisms. |

**Clinical TLS = Laboratory TLS + ≥1 clinical sign → Oncologic emergency**

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## Pathophysiology: The Metabolic Cascade

### Step 1: Tumor Cell Lysis

- Chemotherapy kills cancer cells rapidly
- Intracellular contents flood into bloodstream: K+, phosphate, nucleic acids

### Step 2: Hyperkalemia

- Intracellular K+ (~150 mEq/L) vastly exceeds serum (~5 mEq/L)
- Massive release → ↑ serum K+ to 6–8+ mEq/L
- **Effect on heart:** Peaked T waves → Widened QRS → Ventricular fibrillation → Cardiac arrest
- **Timeline to danger:** Can occur within hours

### Step 3: Hyperuricemia

- Nucleic acids from dead cells → Purine metabolism
- ADA and XO convert purines → **Uric acid**
- Uric acid crystallizes in renal tubules → **Urate nephropathy**
- ↓ GFR → Inability to excrete K+, phosphate, uric acid → Vicious cycle
- **Interpretation:** Elevated urate supports TLS risk; crystal injury depends on burden, urine conditions and clearance, not one diagnostic urate cutoff.

### Step 4: Hyperphosphatemia

- Nucleotide breakdown → ↑ serum phosphate (5–10+ mg/dL possible)
- Phosphate binds calcium → **Hypocalcemia**
- Severe hypocalcemia → Seizures, tetany, arrhythmias
- **Clinical consequence:** Calcium–phosphate precipitation can worsen kidney injury; PTH response does not provide a TLS potassium-treatment rule.

### Step 5: Acute Kidney Injury

- **Urate crystallization** (especially if acidic urine or dehydrated)
- **Phosphate precipitation** in renal tubules
- **Myoglobin deposition** (if rhabdomyolysis from lysis)
- Result: Oliguria, ↑ Cr rapidly (often within 24–48 h)

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## Clinical Presentation (Timeline)

| Time | Finding |
|----|----|
| **6–12 h post-chemo** | Asymptomatic labs: ↑ K+, ↑ uric acid, ↑ phosphate |
| **12–24 h** | Patient may note weakness, palpitations; labs worsening |
| **24–48 h** | **Fulminant phase:** Severe hyperkalemia, arrhythmias, AKI oliguric; seizures if hypocalcemic |
| **\>72 h** | If managed: Gradual recovery; if unmanaged: Cardiac arrest, renal failure |

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## Risk Stratification & Prevention Protocol

### Step 1: Identify Risk at Baseline

**Assess before starting chemotherapy:** - Baseline uric acid, electrolytes (especially K+, PO4), creatinine - Assess tumor burden (size, LDH level) - Screen for pre-existing renal disease

### Step 2: Stratify Risk & Implement Prevention

| Risk Level | Example Tumors | Prevention Protocol |
|----|----|----|
| **Low** | Low-grade lymphomas, solid tumors | Standard hydration, monitor labs q 24 h |
| **Intermediate** | Selected hematologic malignancies after tumor burden, laboratory and treatment assessment | Aggressive hydration, allopurinol, q12h labs |
| **High** | Burkitt lymphoma, blast crisis, bulky AML | **Rasburicase first-line**, aggressive hydration, often q4–6h labs, ICU monitoring |

### Prevention Measures

#### Hydration

- **Hydration goal:** Use indicated isotonic hydration with close urine-output, perfusion, weight, and congestion review. Follow an age/body-size-appropriate oncology protocol; do not force urine targets with more fluid in an anuric or overloaded patient.
- **Fluid:** Use an appropriate isotonic crystalloid for indicated resuscitation; tailor ongoing fluid composition to sodium, losses and volume status. Do not routinely add potassium or phosphate during the high-risk period.
- **Avoid:** Loop diuretics (↑ risk of volume depletion); some protocols use cautious loops if fluid-overloaded

#### Uric Acid Management

| Agent | Mechanism | Use |
|----|----|----|
| **Allopurinol** | Xanthine oxidase inhibitor; reduces new uric acid production but does not remove existing urate | Used for risk-adapted prevention; select with oncology rather than only when rasburicase is unavailable |
| **Rasburicase** | Fungal uricase; degrades uric acid → allantoin | Select for appropriate high-risk or established TLS; contraindicated in G6PD deficiency |
| **Febuxostat** | XO inhibitor; faster than allopurinol | Emerging option; less data in TLS |

**Rasburicase safety:** Use a risk- and protocol-based regimen. G6PD deficiency is a contraindication because of hemolysis/methemoglobinemia risk; follow screening guidance. After dosing, collect and transport uric-acid samples chilled according to the label to prevent falsely low results. [Prescribing information](https://products.sanofi.us/elitek/elitek.html).

#### Electrolyte Monitoring

- **Low risk:** Baseline + q 24 h × 5 days
- **Intermediate:** Baseline + q 12–24 h × 5–7 days
- **High risk or established TLS:** Frequent chemistry, often every 4–6 hours, and appropriate cardiac/clinical monitoring; adjust to the rate of tumor breakdown and metabolic change.

#### Phosphate & Calcium Management

- **Avoid:** Prophylactic calcium (can precipitate in vasculature)
- **Manage:** If hypocalcemic AND symptomatic, then give calcium gluconate IV slowly with continuous cardiac monitoring
- **Phosphate binders:** An oral phosphate binder may be an adjunct, but does not reliably control rapid intracellular phosphate release; reassess for dialysis with severe/refractory complications. Avoid routine aluminum exposure in impaired kidney function.

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## Management of Active TLS

### Hyperkalemia Management

**Urgency:** Severe or rapidly rising hyperkalemia requires immediate assessment and treatment even if the ECG is initially normal. Use ECG findings and clinical risk to guide membrane stabilization while shifting and removing potassium.

| Intervention | Mechanism | Dose |
|----|----|----|
| **Calcium gluconate** | Cardiac membrane stabilization (not K+-lowering) | 1 amp (1 g) IV slowly; repeat q 5 min if peaked T waves |
| **Insulin + Dextrose** | Shift K+ intracellularly | 10 units regular insulin IV + 25 g dextrose (D50W 50 mL) |
| **Albuterol** | β-2 agonist; shift K+ into cells | 10–20 mg nebulized |
| **Sodium bicarb** | Alkalinization; shift K+ intracellularly | Use selectively for clinically important acidemia; bicarbonate is not routine stand-alone hyperkalemia therapy |
| **Loop diuretic** | ↑ K+ excretion (if euvolemic/hypervolemic) | Furosemide 40–80 mg IV q 4–6 h |
| **Potassium binders** | K+-binding resin (slow; not for acute) | Agent-specific dosing and precautions; not a substitute for immediate emergency stabilization, shifting, or dialysis when required |
| **Dialysis** | Definitive removal | For severe/refractory potassium burden or other established indications; do not wait for K above 7 or dialyze solely because of anuria |

**ECG warning signs:** Peaked T waves, conduction slowing, loss of P waves, QRS widening or a sine-wave pattern can occur, but ECG appearance does not reliably map to a potassium concentration. A normal ECG does not exclude dangerous hyperkalemia.

### Hyperuricemia Management

- **Rasburicase:** Select using TLS risk, G 6 PD status, prior doses and oncology protocol; follow the product label rather than automatically dosing every patient.
- **Hydration:** Use only the fluid indicated by perfusion, losses and volume tolerance; reassess frequently in AKI, heart failure or anuria.
- **Monitor:** High-risk/established TLS often needs chemistry every 4–6 hours. After rasburicase, use a prechilled heparinized tube, ice-water transport and assay within 4 hours to avoid falsely low urate.

### Hyperphosphatemia Management

- **Hydration** (dilution)
- **Phosphate binders:** Select any oral binder with the treating team; it is adjunctive and cannot replace timely dialysis for severe phosphate-related complications. Avoid routine aluminum-containing treatment in AKI.
- **Monitor:** Repeat labs in 4–6 hours
- **Avoid calcium** unless symptomatic hypocalcemia (risk of calcification)

### Hypocalcemia Management

- **Monitor:** Assess symptoms, ECG and calcium; use ionized calcium when clinically important, particularly with changing pH or albumin. Check magnesium.
- **Symptomatic only:** If seizures, tetany, or severe arrhythmias
  - Calcium gluconate 1 amp IV in 50 mL D5W or NS over 10 minutes
  - Continuous cardiac monitoring
  - Target: Relieve dangerous symptoms/ECG effects with the minimum calcium needed; do not chase a fixed corrected-calcium threshold in hyperphosphatemia.
- **Magnesium:** Correct a measured clinically important deficit with a renal-function-aware plan; avoid routine replacement to a universal target.

### Acute Kidney Injury Management

- **Oliguria:** Reassess perfusion, obstruction, congestion, and metabolic burden. Urgent KRT may be required for refractory hyperkalemia, acidemia, pulmonary edema, or severe phosphate-related complications; no isolated urate cutoff mandates dialysis.
- **Nonoliguric AKI:** Continue only indicated hydration, with frequent chemistry and volume review. Preserved urine output does not exclude severe metabolic complications.
- **Course:** Recovery varies with cancer burden, treatment response, kidney reserve, and complications; do not promise a fixed 3–7-day recovery.
- **Dialysis indications:**
  - Severe or refractory hyperkalemia despite appropriate stabilization/shifting; do not wait for an arbitrary potassium threshold
  - Severe ongoing metabolic complications despite appropriate treatment; urate above 8 mg/dL alone does not establish a dialysis indication
  - [x] Pulmonary edema, hypervolemia
  - [x] Symptomatic hypocalcemia unresponsive to calcium

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## Prevention of Recurrence

**While tumor lysis continues:** Reassess fluid need, potassium/phosphate/calcium/urate trends and urine output. Established TLS may require tests every 4–6 hours. Redosing urate therapy and changes to anticancer treatment are oncology decisions based on response, risk and the product label, not automatic continuation.

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## Monitoring Checklist

**At baseline (before chemo):** - ☐ Uric acid, BMP (K, PO4, Cr, Ca), LDH - ☐ Assess tumor burden & risk - ☐ Ensure IV access for hydration & drug administration

**During the TLS risk window:** Track potassium, phosphate, calcium, urate, creatinine, urine output, weight, perfusion, and symptoms. High-risk/established disease often requires chemistry every 4–6 hours and cardiac monitoring; reduce frequency only as risk and metabolic trends settle.

**After stabilization:** Reduce monitoring only as the lysis risk and metabolic trend settle. Reassess ongoing hydration and urate therapy with oncology; do not automatically continue rasburicase into days 7–14.

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## Key Clinical Pearls

✓ **TLS risk can often be reduced** — Identify high risk, give rasburicase, hydrate aggressively ✓ **Risk-adapted urate therapy** — Consider indication, G6PD status, and protocol ✓ **Hyperkalemia kills fast** — Peaked T waves = oncologic emergency; stabilize with calcium + shift K+ intracellularly ✓ **Dialysis is your friend** — Don’t hesitate; TLS patients often need RRT ✓ **Hypocalcemia is secondary** — Don’t give prophylactic calcium; avoid calcification ✓ **Peak risk: 24–48 hours** — Most intensive monitoring needed first 2–3 days

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## Clinical Decision Tree

    Patient starting chemo for high-risk malignancy?

    │
    ├─→ YES → Stratify risk (low/intermediate/high)
    │         │
    │         ├─ LOW: Hydration/monitoring plan; urate therapy if indicated by protocol
    │         ├─ INTERMEDIATE: Indicated hydration, usually allopurinol prophylaxis; monitoring by risk
    │         └─ HIGH: Rasburicase, aggressive hydration, often q4–6h labs, ICU monitoring
    │
    └─→ NO → Routine monitoring

    During chemo (48–72 h window):
    │
    ├─ Lab TLS (↑ K, ↑ uric acid, ↑ PO4, ↓ Ca) → Reassess volume; risk-adapted urate therapy and frequent monitoring
    ├─ K+ >6.5 or EKG changes → STAT calcium gluconate + insulin + dextrose + dialysis if refractory
    ├─ Oliguria + AKI → Consider CRRT/hemodialysis
    └─ Seizures/arrhythmias → ICU admission, continuous monitoring

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## Related Content

**Onconephrology Hub:** - Tumor Lysis Syndrome Comprehensive Review — Detailed pathophysiology and advanced management - Cancer Electrolyte Emergencies — Related metabolic complications

**Student Resources:** - Student Handout: AKI Staging — Framework for acute kidney injury assessment - Hyperkalemia Management Guide — Detailed electrolyte management

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## References

- Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004;127(1):3. [PubMed](https://pubmed.ncbi.nlm.nih.gov/15384972/)
- McBride A, Trifilio S, Baxter N, et al. Managing Tumor Lysis Syndrome in the Era of Novel Cancer Therapies. J Adv Pract Oncol. 2017;8(7):705-720. [PubMed](https://pubmed.ncbi.nlm.nih.gov/30333933/)
- Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med. 2011;364(19):1844. [PubMed](https://pubmed.ncbi.nlm.nih.gov/21561350/)
- Perissinotti AJ, Bishop MR, Bubalo J, et al. Expert consensus guidelines for the prophylaxis and management of tumor lysis syndrome in the United States: Results of a modified Delphi panel. Cancer Treat Rev. 2023;120:102603. [PubMed](https://pubmed.ncbi.nlm.nih.gov/37579533/)

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**Study Tips:** - **Memorize Cairo-Bishop criteria** — 2 of 4 labs = Lab TLS - **Know the EKG progression** — Peaked T waves → Widened QRS → Sine wave - **Rasburicase is your drug** — Reliable, fast onset, reliably reduces uric acid - **Calcium + Insulin first** — Stabilize heart, then shift K+ into cells - **Dialysis:** Use refractory clinical/metabolic complications and trajectory; do not wait for K above 7

*Created: 2026-02-28*

### Also on this topic

The same subject at other levels of depth.

- **Lecture:** [🚨 Tumor Lysis Syndrome (TLS)](https://urinenephrology.org/2025_UDPA_Lectures_Live/aki/TLS.html)
- **Interactive case:** [Tumor Lysis Syndrome](https://urinenephrology.org/2025_UDPA_Lectures_Live/cases/case12_enhanced.html)
- **Clinical Mastery deep dive:** [Tumor Lysis Syndrome in Small Cell Lung Cancer](https://urinenephrology.org/mastery/onconephrology/tls-small-cell-lung-cancer.html)


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