Tumor lysis syndrome resident survival guide

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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

Prevention

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.[2][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

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose
❑ Monitor urine output (80-100 ml/m²/hr)
❑ Record the fluid balance
❑ Monitor electrolytes and creatinine daily
 
 
 
❑ Monitoring for laboratory or clinical TLS criteria for 24-72 hrs

❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose
❑ Monitor urine output (80-100 ml/m²/hr)
❑ Record the fluid balance
❑ Monitor electrolytes and creatinine eevry 8-12 hours
❑ Administer allopurinol*
❑ Add 0.15 mg/kg rasburicase in pediatric patients with uric acid level ≥ 7.5 mg/dl for 1-7 days (average 3 days)

 
 
 
❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose
❑ Monitor urine output (80-100 ml/m²/hr)
❑ Record the fluid balance
❑ Monitor electrolytes and creatinine every 4-6 hours
❑ Ensure continuous cardiac monitoring
❑ Consult nephrology
❑ Delay tumor therapy (individual clinical judgement)
❑ Administer 0.20 mg/kg rasburicase in pediatric patients with uric acid level > 7.5 mg/dl for 1-7 days (average 3 days)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

* Allopurinol administration:

  • In pediatric patients:
    • 50-100 mg/m2 every 8 hours, orally, maximum dose of 300 mg/m2/d, OR
    • 10 mg/kg/day divided every 8 hours, orally, maximum dose of 800 mg/d
  • In adults:
    • 100 mg/m2/dose every 8 hours (10 mg/kg/d divided every 8 hours), orally, maximum dose of 800 mg/d, OR
    • 200-400 mg/m2/d, 1 to 3 IV doses, maximum dose 600 mg/d (when oral allopurinol can not be administered)[1]

Initial Approach

 
 
 
 
Characterize the symptoms:

Nausea
Vomiting
Anorexia
Lethargy
Diarrhea
Hematuria
Seizures
❑ Muscle cramps
Syncope
Flank pain
Heart failure
Tetany
Arrhythmia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order tests:

Uric acid
Potassium
Calcium
Phosphate
LDH
Creatinine


❑ Order an EKG
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient have the criteria for the diagnosis of tumor lysis syndrome?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
Laboratory TLS
 
Laboratory TLS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Stratify the patient by the risk of developing TLS
❑ Initiate the appropriate preventive measures (see the algorithm above)
 
❑ Continuous cardiac monitoring
❑ Renal consult
❑ Above mentioned laboratory tests every 4-6 hours
❑ Normalize electrolyte abnormalities
Rasburicase 0.2 mg/kg
❑ Hydration ± loop diuretic
 
❑ 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
 

Management of the Complications

 
 
 
 
 
 
 
Complications of TLS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperphosphatemia
 
Hypocalcemia
 
Hyperkalemia
 
Hyperuricemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate ( ≥2.1 mmol/L)

❑ Avoid phosphate in IV solutions
❑ Provide adequate hydration
❑ Administer phosphate binders:

Aluminium hydroxide: 50-150 mg/kg/day every 6 hrs, orally or by NG tube
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
❑ Adjust the dose of drugs excreted by the kidneys
 
 
 
 
 
 
 
 
 
 

Do's

  • Consider additional risk factors that place the patient in a higher risk group:
  • Consider the following during the administration of allopurinol:
    • 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.
  • Administered IV rasburicase over 30 min.
    • Note that rasburicase is not approved for adults and geriatric population in United States.
  • Immediately initiate hyperkalemia management in case of severe (>7 mg/dl) hyperkalemia, or if the EKG shows widening of QRS complex.
  • Ensure that dialysis should be accessible to all high risk disease patients before cytotoxic chemotherapy is started.
  • Request a renal consult for all high risk disease patients.

Dont's

  • Do not administer calcium, phosphate and potassium with the initial hydration fluids.
  • Alkalinization is currently not recommended for prevention or treatment of TLS.
  • Do not administer rasburicase in patients with G6PD deficiency, pregnant women, lactating women or in the case of a history of anaphylactic reaction.
  • Do not treat with allopurinol treatment after a course of rasburicase.
  • Do not administer sodium bicarbonate and calcium through the same IV line.

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. 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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