Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) constitutes the most frequent oncologic emergency.

It is developed by lysis of tumor cells, during or within 7 days of chemotherapy.

The output of large amounts of potassium, phosphate, and nucleic acid, can result in characteristic electrolyte disturbances and cause the

characteristic life-threatening arrhythmias (from electrolyte imbalances) and AKI (from hyperuricemia or hyperphosphatemia).

TLS can occur spontaneously in any tumor type with a high proliferative rate, large tumor burden, or high sensitivity to cytotoxic agents especially

clinically aggressive and highly aggressive lymphomas (the Burkitt subtype) and T-cell acute lymphoblastic leukemia (ALL).

The increase in frequency and severity of TLS in hematologic cancers is associated with the emergence of effective targeted anticancer drugs.

Hyperkalemia

Happens in initial stages, 12-24 hours post chemotherapy

The most dangerous electrolyte abnormality and usually requires urgent and aggressive treatment as it can quickly develop into an arrhythmia

Standardized treatment consists of short infusion of calcium gluconate or chloride with continuous cardiac monitoring, IV infusion of insulin and

glucose, and nebulized beta-2 agonist (albuterol) +/- loop diuretic to promote excretion of potassium and calcium gluconate; start dialysis in

refractory cases

Hypocalcemia

Secondary to hyperphosphatemia caused by the release from lysed cells

Can lead to fatal cardiac arrhythmia, tetany, and seizures

Treat symptomatic hypocalcemia with lowest dose of IV calcium gluconate or chloride to relief symptoms, or by correcting serum phosphorus

levels; Reserve IV calcium replacement for patients with EKG changes, tetany, and convulsions

Hyperuricemia

Develops 48-72 hours post chemotherapy

Influx of nucleic acids from lysed cells is released into the blood and converted to uric acid by xanthine oxidase. Renal failure happens due to an

increase of uric acid passage and secretions by the renal tubule normally recycled by purine salvage pathways.

Urine alkalinization use is controversial but may be considered in cases of no rasburicase and severe hyperuricemia

Hyperphosphatemia

Typically develops 24-48 hours post chemo when level exceeds renal excretion capacity

Can lead to hypocalcemia

To reduce the risk of hyperkalemia and hyperphosphatemia, continuous modes of renal replacement function are preferred over intermittent

hemodialysis

IV Hydration

Avoid calcium and potassium containing fluids due to the risk of hyperkalemia and hyperphosphatemia with calcium phosphate precipitation from

tumor breakdown2

(Amir Haddad & [email protected]

Hypouricemic Agents

Allopurinol

Rasburicase

Febuxostat

Author,

year

Design/ sample

size

Intervention & Comparison

Outcome

Goldman,

2001

Multicenter RCT

(n=52)

Pediatric patients with leukemia or lymphoma

and at high risk for TLS received allopurinol (300

mg/m2 or 10 mg/kg PO q8h) vs rasburicase (0.2

mg/kg IV daily) for 5-7 days

mean uric acid AUC(0-96) was 128 +/- 70 mg/dL.hour for

the rasburicase group vs 329 +/- 129 mg/dL.hour for the

allopurinol group (P <.0001)

86% vs 12% reduction (P <.0001) in initial plasma uric acid

levels in the rasburicase vs allopurinol group shown 4 h

post 1st dose

The study demonstrated more rapid control and lower

levels of plasma uric acid in the rasburicase group

Cortes,

2010

RCT (n=275)

Rasburicase (0.20 mg/kg/d IV days 1-5) vs

rasburicase + allopurinol (rasburicase 0.20

mg/kg/d 1-3 followed by PO allopurinol 300

mg/d 3-5) vs allopurinol (300 mg/d PO d 1-5)

sUA response rate was significantly greater for rasburicase

than for allopurinol (P=.001) in the overall study

population, those at high risk for TLS (89% vs. 68%;

P=0.012), and in patients with baseline hyperuricemia

(90% vs. 53%; P=0.15)

Time to sUA control in hyperuricemic patients was 4 h for

rasburicase, 4 h for rasburicase + allopurinol, and 27 h for

allopurinol

Rasburicase was well tolerated and provided more rapid

uric acid control than allopurinol alone

Vadhan-

Raj, 2012

RCT (n=82)

The best management of TLS is prevention and is usually based on the following risk stratification:

Low risk: observe and monitor S&S, hydration, +/- allopurinol

Intermediate risk: monitoring, hydration, and allopurinol (does not acutely reduce uric acid)

High risk: monitoring, aggressive IV hydration* and rasburicase (CI in G6PD; use allopurinol)

*For severe-risk patients, use aggressive fluid hydration to achieve urine output of 80-100 mL/m2 per hour (without CI for volume

expansion) +/- loop diuretic (if no evidence of acute obstructive uropathy and/or hypovolemia)

Febuxostat is an alternative oral agent in patients who are at intermediate-high risk for TLS and cannot tolerate allopurinol and when rasburicase

is not available or is contraindicated.

Urine alkalinization with sodium bicarbonate has fallen out of favor and is only indicated in patients with metabolic acidosis.

The emergent treatment of TLS involves vigorous hydration and careful monitoring of fluid balance, correcting electrolyte abnormalities, and

possible renal replacement therapy.

Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved January 17, 2021, from

http://www.micromedexsolutions.com/

Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based

review. J Clin Oncol 2008; 26:2767.

Jones GL, Will A, Jackson GH, et al. Guidelines for the management of tumour lysis syndrome in adults and children with haematological

malignancies on behalf of the British Committee for Standards in Haematology. Br J Haematol 2015; 169:661.

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