Tumor lysis syndrome: Difference between revisions

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==Definition==
==Background==
*Typically occurs within 1 to 5 days of initiation of chemotherapy
*Associated with treatment of acute [[leukemia]], Burkitt [[lymphoma]], NHL
**Rarely observed in solid tumors or without prior therapy
*Rapid turnover of tumor cells (spontaneously or after treatment) leading to release of:
**Potassium
**Phosphate
***Binds Ca causing [[hypocalcemia]]
**Uric acid (converted from nucleic acids)


===Risk Factors===
*High cell proliferation rate
*Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
*Extensive BM involvement
*Tumor infiltration of the kidney


Massive release of intracellular products from malignant cells after antitumor rx or spontaneously, resulting in constellation of metabolic and subsequent clinical derangements (see Cairo-Bishop below):
===Cairo-Bishop Definition<ref>Cairo MS and Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br. J. Haematol. 2004; 127(1):3–11.</ref>===
'''Laboratory Tumor Lysis Syndrome'''
*Abnormality in 2 or more of the following, occurring within 3d before or 7d after chemo:
**Uric acid ≥ 8mg/dL or 25% increase from baseline
**Potassium ≥ 6mEq/L or 25% increase from baseline
**Phosphate ≥ 4.5mg/dL or 25% increase from baseline (≥ 6.5 for children)
**Calcium ≤ 7mg/dL or 25% decrease from baseline
'''Clinical Tumor Lysis Syndrome'''
*Laboratory tumor lysis syndrome plus 1 or more of the following:
**Creatinine > 1.5 times upper limit of age-adjusted reference range
**Cardiac dysrhythmia or sudden death
**Seizure


-Hyperuricemia
==Clinical Features==
*Hyperuricemia
**[[Nausea/vomiting]], [[lethargy]], [[renal failure]]
*[[Hyperkalemia]]
**Most immediate life-threatening element (due to [[dysrhythmias]])
*[[Hyperphosphatemia]]
**May combine with Ca to precipiate in renal tubules
*[[Hypocalcemia]]
**Anorexia, cramping, tetany, [[confusion]], [[seizures]], [[V-tach]]/[[torsades]]
*[[Acute Renal Failure]]
**Most common cause of morbidity
**Usually results from uric acid precipitation within renal tubules


-Hyperkalemia
==Differential Diagnosis==
{{Oncologic emergencies DDX}}


-Hyperphosphatemia
==Evaluation==
 
===Work Up===
-Hypocalcemia
*CBC
 
*Chemistry
== ==
**Elevated Cr
 
*Calcium, phosphate
 
*Uric Acid
==Etiology==
*LDH - >2-3 fold increase stratifies into higher TLS risk<ref>Held-Warmkessel J. Preventing & Managing Tumor Lysis Syndrome. Oncology Times: 25 April 2010 - Volume 32 - Issue 8 - pp 1-7</ref>
 
*[[Urinalysis]]
 
*[[ECG]]
* Usually occurs within 1-5 days of starting chemotherapy or radiation for rapidly growing tumors (esp leukemia/lymphoma)
**[[Hyperkalemia]], [[hypocalcemia]]
* Can present spontaneously in certain lymphoproliferative malignancies before they are diagnosed
;Avoid IV contrast
* Categorized according to tumor classification (heme v. solid tumor) and relationship to antitumor rx (spontaneous v. treatment-associated)
 
==Epidemiology==
 
 
-Most common among non-Hodgkin lymphoma (esp. Burkitt lymphoma), acute and chronic leukemia
 
-Solid tumors (rare): metastatic breast CA, small cell and NSC lung CA, seminoma, invasive thymoma, metastatic medulloblastoma, Merkel cell CA, ovarian CA, rhabdomyosarcoma, metastatic melanoma, vulvar CA
 
 
==Pathophysiology==
 
 
-Lysed tumor cells release nucleic acid metabolites, phosphorus and potassium into circulation
 
-Nucleic acids degrade into purine metabolites which are then processed by xanthine oxidase into uric acid (excreted in urine)
 
-Phosphorus binds calcium leading to hypocalcemia
 
 
==Risk Factors==
 
 
-High cell proliferation rate
 
-Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
 
-Extensive BM involvement
 
-Tumor infiltration of the kidney
 
== ==
 
 
==Signs/Symptoms==
 
 
* -Hyperuricemia (nausea, vomiting, lethargy, renal failure)
* -Hyperkalemia (arrythmias)
* -Hyperphosphatemia (renal failure)
* -Hypocalcemia (anorexia, cramping, tetany, confusion, seizures, V tach/torsades)
* Acute renal failure
== ==
 
 
==Work Up==
 
 
* CBC, Chem (including phos, ionized Ca)
* Uric Acid, LDH
* UA
* Lactate
* ECG (hyperK, hypoCa)
 
==Imaging==
 
 
* Avoid IV contrast


==Management==
==Management==
Aggressive hydration - Goal urine output is 3L in 24hr


===[[Hypocalcemia]] Treatment===
*≤7 or 25% decrease in baseline
**Treat only if symptomatic (increased Ca leads to increased Ca/phos deposition), such as widened QRS or ventricular arrhythmias
**[[Calcium gluconate]] 50-200mg IV


* Hypocalcemia (≤ 7mg/dL or 25% dec in baseline)
{{Hyperphosphatemia treatment}}
* Calcium gluconate 50-200mg IV (only if symptomatic)
*Consider sevelamer 800-1600mg PO tid to avoid side effects of aluminum toxicity and hypercalcemia from aluminum hydroxide treatment
* Hyperphosphatemia (≥4.5 mg/dL or 25% increase; ≥ 6.5mg/dL in children)
* Aluminum hydroxide (50-150mg/kg PO q4-6h)
* Dialysis if refractory
* Hyperuricemia (≥8mg/dL or 25% increase)
*  Allopurinol 10mg/kg/d PO q8 OR 200-400 mg/m2 IV q12; renally dosed
* Inhibition of xanthine oxidase can last 18-30h
* Acts slowly and only against FUTURE production of uric acid
* Urate Oxidase Rx (eg Rasburicase 0.05-0.2mg/kg IV)
* uric acid final product of purine metabolism in humans; in mammals urate oxidase converts uric acid to allantoin (5-10x more soluble)
* Can be used for BOTH prevention and treatment
* Expensive
* Hyperkalemia (see Hyperkalemia)
 
Diuretics (only if euvolemic)
 
Urine Alkalinization
 
-NaHCO3 to urine pH >= 7.0
 
-uric acid solubility increases in alkaline environment
 
-no better than NS hydration
 
-not currently recommended
 
 
Acute Kidney Injury (Cr > 1.5):
 
-Hydration with NS: goal UO 3L/24h
 
--decreases uric acid concentration in serum and renal tubules and  reduces uric acid precipitation
 
--if vol overload-->dialysis


===Hyperuricemia Treatment===
*≥8 or 25% increase
**[[Allopurinol]]
***Acts slowly; only helpful for preventing future production of uric acid
***10mg/kg/d PO q8 '''OR''' 200-400mg/m2 IV q12; renally dosed
***Inhibition of xanthine oxidase can last 18-30h
**Urate Oxidase
***[[Rasburicase]] 0.05-0.2mg/kg IV
***Can be used for BOTH prevention and treatment
***Uric acid final product of purine metabolism
****Urate oxidase converts uric acid to allantoin (5-10x more soluble)


Dialysis (criteria)
===[[Hyperkalemia]] Treatment===
*Only give Ca for cardiovascular instability (e.g.ventricular arrhythmias, widened QRS)
**Giving Ca leads to increased Ca/phos deposition which leads to renal failure
*See [[Hyperkalemia]] for treatment options


K > 6mEq/L
===[[Dialysis]] Criteria===
 
*Potassium >6
Significant renal insufficiency
*Significant renal insufficiency (Creatinine >10)
 
*Uric Acid >10
Uric Acid > 10 mg/dl
*Symptomatic [[hypocalcemia]]
 
*Serum phosphorus >10
Symptomatic hypocalcemia
*Volume overload
 
Serum phosphorus > 10mg/dl
 


==Disposition==
==Disposition==
*Admit (often to ICU)


==References==
<references/>


Admission
[[Category:Heme/Onc]]
 
==Medication Dosing==
== ==
===Hyperuricemia===
 
*{{MedicationDose|drug=Rasburicase|dose=0.05-0.2 mg/kg|route=IV|context=Urate oxidase (prevention and treatment)|indication=Tumor lysis syndrome|population=Adult|notes=Converts uric acid to allantoin; contraindicated in G6PD deficiency}}
 
*{{MedicationDose|drug=Allopurinol|dose=200-400 mg/m2 q12hr (or 10 mg/kg/day PO divided q8hr)|route=IV/PO|context=Xanthine oxidase inhibitor (prevention only)|indication=Tumor lysis syndrome|population=Adult|notes=Renally dosed; only prevents future uric acid production}}
==*Cairo-Bishop Definitions==
 
 
Laboratory Tumor Lysis SyndromeUric acid level: ≥ 8 mg/dL or 25% increase from baseline
 
Potassium level: ≥ 6.0 mEq/L or 25% increase from baseline
 
Phosphorus: ≥ 6.5 mg/dL for children Phosphorus concentration: ≥ 4.5 mg/dL for adults or 25% increase from baseline
 
Calcium level: ≤ 7 mg/dL or 25% decrease from baseline
 
 
Clinical Tumor Lysis SyndromeLaboratory tumor lysis syndrome plus 1 or more of the following criteria:
 
Creatinine > 1.5 times upper limit of age-adjusted reference range
 
Cardiac dysrhythmia or sudden death Seizure


===Symptomatic Hypocalcemia===
 
*{{MedicationDose|drug=Calcium gluconate|dose=50-200 mg|route=IV|context=Symptomatic hypocalcemia|indication=Tumor lysis syndrome|population=Adult|notes=Treat only if symptomatic; avoid overcorrection (increases Ca-phos deposition)}}
==Source==
 
 
EM Practice March '10
 
 
 
 
[[Category:Heme/Onc]]

Latest revision as of 17:57, 20 March 2026

Background

  • Typically occurs within 1 to 5 days of initiation of chemotherapy
  • Associated with treatment of acute leukemia, Burkitt lymphoma, NHL
    • Rarely observed in solid tumors or without prior therapy
  • Rapid turnover of tumor cells (spontaneously or after treatment) leading to release of:
    • Potassium
    • Phosphate
    • Uric acid (converted from nucleic acids)

Risk Factors

  • High cell proliferation rate
  • Large tumor burden (LDH) > 1500 IU/L, WBC ≥ 50 x 103 cells/L
  • Extensive BM involvement
  • Tumor infiltration of the kidney

Cairo-Bishop Definition[1]

Laboratory Tumor Lysis Syndrome

  • Abnormality in 2 or more of the following, occurring within 3d before or 7d after chemo:
    • Uric acid ≥ 8mg/dL or 25% increase from baseline
    • Potassium ≥ 6mEq/L or 25% increase from baseline
    • Phosphate ≥ 4.5mg/dL or 25% increase from baseline (≥ 6.5 for children)
    • Calcium ≤ 7mg/dL or 25% decrease from baseline

Clinical Tumor Lysis Syndrome

  • Laboratory tumor lysis syndrome plus 1 or more of the following:
    • Creatinine > 1.5 times upper limit of age-adjusted reference range
    • Cardiac dysrhythmia or sudden death
    • Seizure

Clinical Features

Differential Diagnosis

Oncologic Emergencies

Related to Local Tumor Effects

Related to Biochemical Derangement

Related to Hematologic Derangement

Related to Therapy

Evaluation

Work Up

Avoid IV contrast

Management

Aggressive hydration - Goal urine output is 3L in 24hr

Hypocalcemia Treatment

  • ≤7 or 25% decrease in baseline
    • Treat only if symptomatic (increased Ca leads to increased Ca/phos deposition), such as widened QRS or ventricular arrhythmias
    • Calcium gluconate 50-200mg IV

Hyperphosphatemia treatment

  • Treat the underlying cause
  • Restrict calcium phosphate intake
  • IV Normal Saline (if normal renal fx)
  • Acetazolamide (500mg IV q6hr) - if normal renal function
  • Phosphate Binder - Aluminum hydroxide (50-150mg/kg PO q4-6h) - limited effect
  • Dialysis if refractory
  • Consider sevelamer 800-1600mg PO tid to avoid side effects of aluminum toxicity and hypercalcemia from aluminum hydroxide treatment

Hyperuricemia Treatment

  • ≥8 or 25% increase
    • Allopurinol
      • Acts slowly; only helpful for preventing future production of uric acid
      • 10mg/kg/d PO q8 OR 200-400mg/m2 IV q12; renally dosed
      • Inhibition of xanthine oxidase can last 18-30h
    • Urate Oxidase
      • Rasburicase 0.05-0.2mg/kg IV
      • Can be used for BOTH prevention and treatment
      • Uric acid final product of purine metabolism
        • Urate oxidase converts uric acid to allantoin (5-10x more soluble)

Hyperkalemia Treatment

  • Only give Ca for cardiovascular instability (e.g.ventricular arrhythmias, widened QRS)
    • Giving Ca leads to increased Ca/phos deposition which leads to renal failure
  • See Hyperkalemia for treatment options

Dialysis Criteria

  • Potassium >6
  • Significant renal insufficiency (Creatinine >10)
  • Uric Acid >10
  • Symptomatic hypocalcemia
  • Serum phosphorus >10
  • Volume overload

Disposition

  • Admit (often to ICU)

References

  1. ↑ Cairo MS and Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br. J. Haematol. 2004; 127(1):3–11.
  2. ↑ Held-Warmkessel J. Preventing & Managing Tumor Lysis Syndrome. Oncology Times: 25 April 2010 - Volume 32 - Issue 8 - pp 1-7

Medication Dosing

Hyperuricemia

  • Rasburicase 0.05-0.2 mg/kg IV — Converts uric acid to allantoin; contraindicated in G6PD deficiency
  • Allopurinol 200-400 mg/m2 q12hr (or 10 mg/kg/day PO divided q8hr) IV/PO — Renally dosed; only prevents future uric acid production

Symptomatic Hypocalcemia

  • Calcium gluconate 50-200 mg IV — Treat only if symptomatic; avoid overcorrection (increases Ca-phos deposition)
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