Tumor lysis syndrome resident survival guide: Difference between revisions

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{{familytree | | | | | B01 | | | | B02 | | | | B03 | | | B01= <div style="float: left; text-align: left; height: 25em; width: 20em; padding:1em;"> '''Low Risk Disease (LRD):'''<br>
{{familytree | | | | | B01 | | | | B02 | | | | B03 | | | B01= <div style="float: left; text-align: left; height: 25em; width: 20em; padding:1em;"> '''Low Risk Disease (LRD):'''<br>
----
----
❑ Solid tumors <br> ❑ [[Multiple myeloma]] <br> ❑ Indolent [[Non-Hodgkin's lymphoma]] <br>❑[[Hodgkin's lymphoma]]<br> ❑ [[AML]] with WBC count ≤25,000 cells/μL and LDH < 2× ULN <br> ❑ [[CLL]] with WBC count < 50,000 cells/μL, treated only with [[alkylating agents]] <br> ❑ [[CML]]<br>
❑ Solid tumors <br> ❑ [[Multiple myeloma]] <br> ❑ Indolent [[Non-Hodgkin's lymphoma]] <br>❑ [[Hodgkin's lymphoma]]<br> ❑ [[AML]] with WBC count ≤25,000 cells/μL and LDH < 2× ULN <br> ❑ [[CLL]] with WBC count < 50,000 cells/μL, treated only with [[alkylating agents]] <br> ❑ [[CML]]<br>
</div>|B02=<div style="float: left; text-align: left; height: 27em; width: 20em; padding:1em;"> '''Intermediate Risk Disease (IRD):'''<br>
</div>|B02=<div style="float: left; text-align: left; height: 27em; width: 20em; padding:1em;"> '''Intermediate Risk Disease (IRD):'''<br>
----❑ Bulky or advanced stage solid tumors <br> ❑ [[Plasma cell leukemia]] <br> ❑ Stage III/IV [[Non-Hodgkin's lymphoma]] with LDH > 2xULN <br> ❑[[AML]] with WBC count ≤25,000 cells/μL and LDH > 2× ULN OR [[AML]] with WBC count 25,000-100,000 cells/μL <br> ❑ [[CLL]] treated with [[fludarabine]] or [[rituximab]] or CML with WBC count > 50,000 cells/μL <br> ❑ [[ALL]] with WBC < 100,000 cells/μL and LDH > 2xULN<br>❑ [[Burkitt's lymphoma]] stage I/II with LDH < 2x ULN<br>
----❑ Bulky or advanced stage solid tumors <br> ❑ [[Plasma cell leukemia]] <br> ❑ Stage III/IV [[Non-Hodgkin's lymphoma]] with LDH > 2xULN <br> ❑[[AML]] with WBC count ≤25,000 cells/μL and LDH > 2× ULN OR [[AML]] with WBC count 25,000-100,000 cells/μL <br> ❑ [[CLL]] treated with [[fludarabine]] or [[rituximab]] or CML with WBC count > 50,000 cells/μL <br> ❑ [[ALL]] with WBC < 100,000 cells/μL and LDH > 2xULN<br>❑ [[Burkitt's lymphoma]] stage I/II with LDH < 2x ULN<br>
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❑ [[Diffuse large B cell lymphoma]]</div>|B03=<div style="float: left; text-align: left; height: 25em; width: 20em; padding:1em;">'''High Risk Disease (HRD):'''<br>
❑ [[Diffuse large B cell lymphoma]]</div>|B03=<div style="float: left; text-align: left; height: 25em; width: 20em; padding:1em;">'''High Risk Disease (HRD):'''<br>
----
----
❑ [[AML]] with WBC count > 100,000 cells/μL <br> ❑ [[ALL]] with WBC >100,000 cells/μL AND/OR LDH > 2xULN <br> ❑[[Burkitt's lymphoma]] stage III/IV with LDH ≥ 2x ULN <br> ❑ [[Lymphoblastic lymphoma]] stage III/IV with LDH ≥ 2x ULN <br>❑ IRD with renal dysfunction<br>❑ IRD with uric acid, potassium or phosphate above ULN<br>
❑ [[AML]] with WBC count > 100,000 cells/μL <br> ❑ [[ALL]] with WBC >100,000 cells/μL AND/OR LDH > 2xULN <br> ❑ [[Burkitt's lymphoma]] stage III/IV with LDH ≥ 2x ULN <br> ❑ [[Lymphoblastic lymphoma]] stage III/IV with LDH ≥ 2x ULN <br>❑ IRD with renal dysfunction<br>❑ IRD with uric acid, potassium or phosphate above ULN<br>
</div>}}
</div>}}



Revision as of 17:24, 20 January 2014


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Twinkle Singh, M.B.B.S. [2]

Definition

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities resulting from rapid lysis of malignant cells and massive release of cell breakdown products into the blood among patients with hematologic malignancies treated with chemotherapy. Metabolic complications include hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia and hyperuricosuria.[1]

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Tumor lysis syndrome is a life-threatening condition and must be treated as such irrespective of the causes.

Common Causes

Classification

Cairo and Bishop classified and graded TLS as laboratory tumor lysis syndrome (LTLS) and clinical tumor lysis syndrome (CTLS).

Cairo and Bishop Definition for Laboratory Tumor Lysis Syndrome (LTLS)[1]

LTLS is considered to be present if 2 or more of the following serum abnormalities are present within 3 days before or 7 days after cytotoxic therapy.

Element Value Change from baseline
Uric acid ≥476 μmol/L or 8 mg/dL 25 % increase
Potassium ≥6 mmol/L or 6mg/L 25 % increase
Phosphorus ≥2.1 mmol/L for children
≥1.45 mmol/L for adults
25 % increase
Calcium ≤1.75 mmol/L 25% decrease

Cairo and Bishop Definition and Grading for Clinical Tumor Lysis Syndrome (CTLS)[1]

Clinical tumor lysis syndrome is said to be present if LTLS is present plus 1 or more of the following clinical correlations:

Complication Grade
0 1 2 3 4 5
Creatinine ≤1.5×ULN 1.5×ULN >1.5-3.0×ULN >3-6×ULN >6×ULN Death
Cardiac arrhythmia None Intervention not indicated Medical intervention indicated,
but not urgently
Controlled with a device or
symptomatically and incompletely
controlled medically
Life threatening Death
Seizure None - One well controlled generalized seizure OR
infrequent multiple focal motor seizures
not affecting activities of daily living
poorly controlled seizure disorder,
seizure with altered consciousness
Status epilepticus,
intractable epilepsy
Death

ULN: Upper limit of normal

Modified LTLS and CTLS criteria by Howard et al[2]

  • CTLS is considered to be present in cases of any cardiac dysrhythmia, symptomatic hypocalcemia or acute kidney injury is present along with LTLS.
  • LTLS is considered to be present if 2 or more of the following serum abnormalities are present during the same 24 hour period within 3 days or 7 days after cytotoxic therapy.
Element Value
Uric acid ≥ 476 μmol/L or 8 mg/dL, > ULN for age in children
Potassium ≥ 6 mmol/L or 6mg/L
Phosphorus ≥ 2.1 mmol/L for children, ≥ 1.45 mmol/L for adults
Calcium Corrected calcium ≤ 1.75 mmol/L or, ionized calcium < 0.3 mmol/L

Prevention of TLS

Shown below is an algorithm summarizing the approach to tumor lysis syndrome according to the guidelines by American Society of Clinical oncology and an expert TLS panel consensus.[3][1]

 
 
 
 
 
 
 
 
 
 
Risk assessment of patients for TLS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low Risk Disease (LRD):

❑ Solid tumors
Multiple myeloma
❑ Indolent Non-Hodgkin's lymphoma
Hodgkin's lymphoma
AML with WBC count ≤25,000 cells/μL and LDH < 2× ULN
CLL with WBC count < 50,000 cells/μL, treated only with alkylating agents
CML

 
 
 
Intermediate Risk Disease (IRD):

❑ Bulky or advanced stage solid tumors
Plasma cell leukemia
❑ Stage III/IV Non-Hodgkin's lymphoma with LDH > 2xULN
AML with WBC count ≤25,000 cells/μL and LDH > 2× ULN OR AML with WBC count 25,000-100,000 cells/μL
CLL treated with fludarabine or rituximab or CML with WBC count > 50,000 cells/μL
ALL with WBC < 100,000 cells/μL and LDH > 2xULN
Burkitt's lymphoma stage I/II with LDH < 2x ULN

Lymphoblastic lymphoma stage I/II with LDH < 2x ULN

Diffuse large B cell lymphoma
 
 
 
High Risk Disease (HRD):

AML with WBC count > 100,000 cells/μL
ALL with WBC >100,000 cells/μL AND/OR LDH > 2xULN
Burkitt's lymphoma stage III/IV with LDH ≥ 2x ULN
Lymphoblastic lymphoma stage III/IV with LDH ≥ 2x ULN
❑ IRD with renal dysfunction
❑ IRD with uric acid, potassium or phosphate above ULN

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Wait and watch approach with close monitoring
❑ Hydration
 
 
 
❑ Monitoring for laboratory or clinical TLS criteria for 24-72 hrs

❑ Hydration

♦ 2-3 L/m²/day IV of a one quarter NS/5%dextrose
♦ Urine out maintained up to 80-100 ml/m²/hr

Allopurinol administration†
❑ ±Single dose of rasburicase in pediatric patients

♦ In intermediate risk patients with uric acid level < 7.5 mg/dl: 0.15 mg/kg for 1-7 days (average 3 days)
 
 
 
ICU admission
Nephrology consult
❑ Monitoring for development of laboratory or clinical TLS every 4-6 hours after initiation of chemotherapy
❑ Hydration
❑ Delay tumor therapy (individual clinical judgement)
❑ Cardiac monitoring

Rasburicase in pediatric patients

♦ In high risk patients with uric acid level > 7.5 mg/dl: 0.20 mg/kg for 1-7 days (average 3 days)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Allopurinol administration:

  • In pediatric patients: 50-100 mg/m2 every 8 hours orally (maximum dose-300 mg/m2/d) or 10 mg/kg/day divided every 8 hours (maximum dose-800 mg/d)
  • In adults: 100 mg/m2/dose every 8 hours (10 mg/kg/d divided every 8 hours) given orally (maximum dose-800 mg/d) or 200-400 mg/m2/day in 1-3 divided doses given IV (maximum, 600 mg/d)[1]

Management of Established TLS

 
 
 
 
 
 
 
 
 
 
 
 
Patient diagnosed with a hematologic malignancy
or a solid tumor (rarely)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Characterize the symptoms:

Nausea
Vomiting
Anorexia
Lethargy
Diarrhea
Hematuria
Seizures
❑ Muscle cramps
Syncope
❑ Flank pain
Heart failure
Tetany
❑ Cardiac dysrhythmias
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order TLS screen

Uric acid
Potassium
Calcium
Phosphate
LDH
❑ Creatinine
❑ Cardiac monitoring (EKG)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient positive for TLS screen ?
(See criteria for LTLS and CTLS above)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Risk stratify as above and manage accordingly
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Intensive care in ICU
❑ Continuous cardiac monitoring
❑ Renal consult
❑ Above mentioned laboratory tests every 4-6 hours
❑ Normalize electrolyte abnormalities
Rasburicase 0.2 mg/kg
❑ Hydration ± loop diuretic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperphosphatemia
 
 
 
Hypocalcemia
 
 
Hyperkalemia
 
 
 
 
Hyperuricemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate ( ≥2.1 mmol/L)

❑ Avoid IV phosphate
❑ Adequate hydration
Phosphate binders

Aluminium hydroxide: 50-150 mg/kg/day every 6 hrs
Calcium carbonate: 30-40 mg/kg with each meal
Lanthanum carbonate: 500-1000 mg with each meal
Sevelamer

Severe


Hemodialysis
Peritoneal dialysis
❑ Continuous venovenous hemofiltration
 
 
 
Asymptomatic

❑ No treatment required
Symptomatic


Calcium gluconate 50-100 mg/kg IV, given slowly with EKG monitoring
❑ If phosphate levels are high

♦ Renal consult
 
 
Asymptomatic ( ≥ 6.0 mmol/L)

❑ Avoid IV or oral potassium intake
Sodium polystyrene sulfonate 1 g/kg with 50 % sorbitol
❑ Cardiac monitoring


Severe ( > 7 mmol/L)/ Symptomatic:


❑ Above mentioned actions plus:
❑ Rapid acting insulin 0.1 U/kg IV plus glucose infusion (25 % dextrose 2 ml/kg)
❑ Calcium gluconate 100-200 mg/kg/dose slow infusion with ECG monitoring for arrhythmias.
Sodium bicarbonate 1-2 mEq/kg IV push
Albuterol inhalation
Hemodialysis
 
 
 
 
Established hyperuricemia

❑ Hydration

♦ 2-3 L/m²/day IV of a one quarter NS/5%dextrose
♦ Urine out maintained up to 80-100 ml/m²/hr
Allopurinol administration
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient responds?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Renal dysfunction (Uremia)
 
 
 
 
 
 
 
 
 
❑ Continue treatment
❑ Continue laboratory monitoring
❑ Continue cardiac monitoring
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Fluid and electrolyte management
❑ Uric acid and phosphate management
Hemodialysis
Peritoneal dialysis
Hemofiltration
♦ Continuous venovenous hemofiltration
♦ Continuous arterial-venous hemodialysis
♦ Continuous arterial-venous hemodialysis
♦ Continuous veno-venous hemodialysis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Do's and Dont's

Risk stratification

  • Additional risk factors that place a patient in a higher risk group:

Prevention and Management of TLS

  • Calcium, phosphate and potassium should not be administered with initial hydration fluids.
  • Loop diuretics are recommended in case urine output is not maintained adequately, but contraindicated in hypovolemia, dehydration and obstructive nephropathy.
  • Alkalinization is currently not recommended for prevention or treatment of TLS.
  • Allopurinol administration :
    • Start treatment 1-2 days before induction therapy and continue till 3-7 after the chemotherapy or until the serum values are normalized.
    • Reduce dose by 50 % in cases of renal insufficiency.
    • Reduce doses of 6-mercaptopurine and azathioprine by 65-75% if administered with allopurinol.
    • Also adjust doses of dicumarol, uricosuric drugs, cytotoxic drugs and thiazide diuretics if they are administered with allopurinol.
  • Rasburicase administration:
    • Contraindicated in G6PD deficiency or history of anaphylactic reaction.
    • Administered IV over 30 min.
    • Indicated in patients with pre-existing hyperuricemia instead of allopurinol.
    • Indicated if hyperuricemia persists in intermediate risk disease despite use of allopurinol.
    • Not approved for adults and geriatric population in United States.
    • Allopurinol treatment after rasburicase is not required.
  • Hyperkalemia management
    • Immediate management is recommended in case of severe (>7 mg/dl) hyperkalemia, or if EKG shows widening of QRS complex.
    • Sodium bicarbonate and calcium should not be administered through the same IV line.
    • Cardiac monitoring should be done continuously.

Monitoring Guidelines

  • In pediatrics high risk patients, TLS screen should be done every 4-6 hrs after induction chemotherapy.
  • TLS screen include following serum lab values:
  • Uric acid should be monitored in all patients every 6-8 hrs after chemotherapy until normalization of LDH value.
  • All adult intermediate risk disease patients should be monitored up to 24 hours after chemotherapy.
  • Likelihood of developing TLS is minimal if it does not occur after 2 days of chemotherapy.
  • Dialysis should be accessible to all high risk disease patients before cytotoxic chemotherapy is started.
  • Renal consult should be placed for all high risk disease patients.

References

  1. 1.0 1.1 1.2 1.3 1.4 Coiffier B, Altman A, Pui CH, Younes A, Cairo MS (2008). "Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review". J Clin Oncol. 26 (16): 2767–78. doi:10.1200/JCO.2007.15.0177. PMID 18509186.
  2. Howard SC, Jones DP, Pui CH (2011). "The tumor lysis syndrome". N Engl J Med. 364 (19): 1844–54. doi:10.1056/NEJMra0904569. PMC 3437249. PMID 21561350.
  3. Cairo, MS.; Coiffier, B.; Reiter, A.; Younes, A.; Cairo, MS.; Coiffier, B.; Reiter, A.; Younes, A.; Baruchel, A. (2010). "Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus". Br J Haematol. 149 (4): 578–86. doi:10.1111/j.1365-2141.2010.08143.x. PMID 20331465. Unknown parameter |month= ignored (help)


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