Cancer Complications

TUMOR LYSIS SYNDROME

Jarett L. Feldman

Matthew J. Matasar

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

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:

	Allopurinol	Rasburicase
Mechanism of Action	Xanthine oxidase inhibitor	Urate oxidase (functional enzyme)
S/e	Allergic rxn (skin rash & urticaria), fever, Steven-Johnson	Skin rash, nausea, vomiting & hypersensitivity (rare cases of anaphylaxis)
Other	Does NOT lower pre-existing UA levels Requires dose adjustment per CrCl Can lead to elevated levels of hypoxanthine that can cause renal failure	Decreases the level of UA by 0.5 to 1 mg/dL w/in 4 h of administration Need to test for G6PD deficiency Used in cases of high-risk TLS 10% incidence of Ab formation