Tumor lysis syndrome resident survival guide: Difference between revisions
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==Do's and Dont's== | ==Do's and Dont's== | ||
===Risk stratification=== | ===Risk stratification=== | ||
* | * Consider additional risk factors that place the patient in a higher risk group: | ||
*:* Bulky disease ( > 10 cm) | *:* Bulky disease ( > 10 cm) | ||
*:* [[LDH]] > 2x upper limit of normal | *:* [[LDH]] > 2x upper limit of normal | ||
Line 164: | Line 164: | ||
*:* High proliferation rate of tumor and rapid response to therapy | *:* High proliferation rate of tumor and rapid response to therapy | ||
*:* Baseline plasma [[uric acid]] > 7.5 mg/dl | *:* Baseline plasma [[uric acid]] > 7.5 mg/dl | ||
===Prevention and Management of TLS=== | ===Prevention and Management of TLS=== | ||
* [[Calcium]], [[phosphate]] and [[potassium]] should not be administered with initial hydration fluids. | * [[Calcium]], [[phosphate]] and [[potassium]] should not be administered with initial hydration fluids. |
Revision as of 21:46, 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
- Acute lymphoblastic leukemia
- Acute myeloid leukemia
- Burkitt's lymphoma
- Chronic lymphocytic leukemia
- Chronic myeloid leukemia
- Multiple myeloma
- Non-Hodgkin's lymphoma
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 | 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 | High Risk Disease (HRD): ❑ AML with WBC count > 100,000 cells/μL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑ 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 | ❑ 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 | |||||||||||||||||||||||
Does the patient have the criteria for the diagnosis of tumor lysis syndrome? | |||||||||||||||||||||||
No | Yes | ||||||||||||||||||||||
❑ Stratify the patient by the risk of developing TLS ❑ Initiate the appropriate preventive measures (see the algorithm above) | ❑ 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
Severe ❑ Hemodialysis ❑ Peritoneal dialysis ❑ Continuous venovenous hemofiltration | Asymptomatic ❑ No treatment required ❑ Calcium gluconate 50-100 mg/kg IV, given slowly with EKG monitoring
| Asymptomatic ( ≥ 6.0 mmol/L) ❑ Avoid IV or oral potassium intake 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
| ||||||||||||||||||||||||||||||||
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 and Dont's
Risk stratification
- Consider additional risk factors that place the patient in a higher risk group:
- Bulky disease ( > 10 cm)
- LDH > 2x upper limit of normal
- Oliguria
- Dehydration
- Pre-existing renal failure
- High proliferation rate of tumor and rapid response to therapy
- Baseline plasma uric acid > 7.5 mg/dl
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:
- Rasburicase is contraindicated in G6PD deficiency, pregnant women, lactating women or in the case of a 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
- ↑ 1.0 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.
- ↑ 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
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