Pocket Oncology (Pocket Notebook Series), 1st Ed.

TUMOR LYSIS SYNDROME

Jarett L. Feldman and Matthew J. Matasar

Definition

TLS is the metabolic abnormalities a/w spontaneous &/or tx-induced cell death that can be potentially fatal in certain situations.

4 key electrolyte abnormalities are:

• Hyperkalemia

• Hyperphosphatemia

• Hypocalcemia

• Hyperuricemia

Cairo and Bishop Classification System for TLS (Br J Haematol 2004;127:3)

Lab TLS: (Abnormality in ≥2 of the following when assessed w/in 3 d before or 7 d after the initiation of cytotoxic Rx)

• UA >8 mg/dL or 25% increase from baseline

• Potassium >6 mEq/L or 25% increase from baseline

• Phosphate >4.5 mg/dL or 25% increase from baseline

• Ca <7 mg/dL or 25% decrease from baseline

Clinical TLS: (Lab TLS + 1 or more of the following clinical abnormalities)

• Increased serum Cr (1.5× the ULN)

• Cardiac arrhythmia or sudden death

• Seizure

Common Malignancies Associated with a High Risk of Developing TLS in Adult Patients

• Acute leukemias (eg, AML & ALL)

• High-grade lymphomas such as Burkitt lymphoma & DLBCL. (Of note, indolent lymphomas rarely cause TLS)

Risk Factors: (Br J Haematol 2010;149:578; N Engl J Med 2011;364:1844)

Common factors a/w TLS are:

• High burden of disease (such as a bulky tumor, extensive met or BM involvement)

• Impaired renal function & nephrotoxins

• High proliferation rate of the CA cells

• Sn of the CA cells to tx & intensity of initial anticancer Rx

• Volume depletion, acidic urine, HoTN

Monitoring

• Monitoring UOP is key along w/maintaining an appropriate fluid balance

• Telemetry is routinely used in certain situations

• Common labs include: UA, phosphate, potassium, Cr, Ca & LDH

• High-risk pts could be monitored in ICU w/frequent measurements of electrolytes, Cr & UA levels

• Intermediate- or low-risk pts require lab monitoring ever 8–12 h & daily respectively

Prophylaxis (DeVita, Hellman, and Rosenberg’s cancer: Principles & practice of oncology 9th ed. Lippincott Williams & Wilkins, 2011; Br J Haematol 2011;154:3)

Ppx is key:

Ppx tx options include the following.

• IV hydration: Usually w/NS, rate depends on clinical situation but for high-risk pts recommended 2500–3000 mL/m2/d or obtain a UOP of 2 mL/kg/h

• Urinary alkalinization (controversial)

• Allopurinol &/or rasburicase Rx (rasburicase in high-risk pts only)

Management (J Clin Oncol 2008;28:16)

Hyperkalemia:

• Clinical s/s:

Asx, cardiac dysrhythmia or ECG changes, muscle cramps, paresthesias, nausea, vomiting, diarrhea & sudden death

• Tx Options:

Mod. & asx, >6 mmol/L:

Sodium polystyrene sulfonate & avoid IV & oral potassium

Sev. (>7 mmol/L) &/or symptomatic:

Sodium polystyrene sulfonate, avoid IV & oral potassium, Ca gluconate (100–200 mg/kg) IV for life-threatening arrhythmias, regular insulin (0.1 Unit/kg IV) + D25 (2 mL/kg) IV, Na bicarbonate (1–2 mEq/kg IV push), loop diuretics, inh β-agonists & in sev. cases dialysis.

Hyperphosphatemia:

• Clinical s/s:

Asx, acute renal failure, 2° hypocalcemia

• Tx Options:

Sevelamer hydroxide, Ca carbonate (should not be used in pts w/elevated Ca), lanthanum carbonate & aluminum hydroxide p.o. 15 mL (50–150 mg/kg/24 h) q6h & sev. cases might require dialysis (Avoid IV phosphate administration during TLS)

Hypocalcemia:

• Clinical s/s:

Asx, NM irritability (including tetany, paresthesias, muscle twitching or cramping, laryngospasm or bronchospasm), cardiac dysfunction (including dysrhythmia, HF), mental status changes (including confusion, delirium, & hallucinations), seizure & sudden death

• Tx Options:

Correct hyperphosphatemia & in symptomatic cases Ca gluconate 50–100 mg/kg IV administered slowly w/ECG monitoring

Hyperuricemia:

• Clinical s/s:

Asx, acute renal failure

• Tx Options:

Allopurinol vs. Rasburicase & in sev. cases HD

Allopurinol vs. Rasburicase: