TLS is a life-threatening condition that occurs when cancer cells are destroyed rapidly, releasing their contents into the bloodstream and thereby overwhelming the body’s normal control systems.1 TLS is characterized by increased levels of uric acid, potassium, and phosphorus, and decreased levels of calcium in the blood. These electrolyte imbalances can lead to kidney damage, heart problems, seizures, and even death.1 Patients with blood cancers are at the highest risk for developing TLS, although TLS has been reported with some solid tumors. The risk for TLS is highest within the first hours and days after starting anticancer therapy.1 TLS can also occur spontaneously, especially with aggressive cancers that have a naturally high rate of cell turnover.1

This handout is specifically designed for patients and caregivers with hematologic malignancies starting anticancer therapies and might be at risk for developing tumor lysis syndrome (TLS).

Educational Handout for PatientsTLS Educational Handout for PatientsTLS

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↑ Uric Acid ↑ Phosphorus ↑ Potassium

Rapid Destruction of Cancer Cells

Cancer Treatment

↓ Calcium

Tumor Lysis Syndrome (TLS)

GI TractKidneysMuscles

HeartNervous System

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What causes TLS?

How can TLS be prevented?

Although TLS can occur spontaneously, it is most commonly associated with blood cancers and, occasionally, solid tumors. Aggressive cancers with high cell turnover (such as Burkitt lymphoma) and high tumor burden are particularly vulnerable.1 The development of new monoclonal antibodies and targeted therapies has increased concern for development of TLS in slower growing cancers, like chronic lymphocytic leukemia (CLL).2 Some of these new cancer treatments are so effective in destroying cancer cells that the body is overwhelmed, increasing the risk for TLS.1 When cancer cells are destroyed rapidly, the kidneys can have difficulty clearing the excess minerals such as phosphorus, potassium, and uric acid from the body. Existing kidney disease or increased age can make this even more difficult; therefore, it is important to discuss your particular risk factors with your doctor before starting cancer treatment.

If you are at risk for TLS, your doctor may recommend starting intravenous (IV) fluids and medication, such as allopurinol or rasburicase, before starting a new cancer treatment to decrease build-up of kidney-damaging uric acid crystals that can form after cancer cells are destroyed.1 Both allopurinol and rasburicase reduce uric acid levels; the decision on which medication to use for TLS prevention is based on level of risk and specific considerations, such as an allergy or presence of a genetic condition known as glucose-6-phosphate dehydrogenase (G6PD) deficiency.1 You should discuss with your doctor which medication is right for you.

In addition, if your cancer therapy is highly potent, your treatment may be started at a low dose and increased gradually to reduce the risk of TLS.3,4 This strategy has been successful in reducing the occurence of TLS with several cancer therapies, including ABT-199 for patients who failed other therapies for CLL.3-5

In some cases, your doctor may suggest hospitalization during cancer treatment to allow for more intense monitoring and fluid management to prevent TLS.1 Your doctor will measure the electrolyte levels in your blood and may administer IV fluids to correct electrolyte imbalances. Continuous heart monitoring may be implemented. Your urine output will be monitored closely to ensure it remains sufficient to keep the kidneys clear and functioning properly.1 If necessary, a diuretic may be used to increase urine output.6

In addition, you should talk with your doctor and healthcare team to see if you need to decrease your intake of foods containing high levels of potassium and/or phosphorus.7 The use of substances that increase uric acid levels also should be avoided, including caffeine, alcohol, vitamin C, vitamin B3, and certain medications (Table 1).1

Table 1. Factors Associated with Increased Risk of Developing TLS1

� Blood cancers (eg, leukemias, lymphomas, myelomas)

� Solid tumors (less common)

� High tumor burden

� Aggressive tumors with rapid cell turnover

� Treatment with highly potent anticancer agents

� Pre-existing kidney disease/kidney involvement by tumor

� Increasing patient age

� Use of certain medications including aspirin, cisplatin, diazoxide, thiazide diuretics, epinephrine, ethambutol, levodopa, methyldopa, pyrazinamide, phenothiazines, and theophylline

� Use of alcohol, vitamin C, vitamin B3 (niacin), and caffeine

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What signs and symptoms should I watch out for?

How is TLS treated?

Table 2 summarizes signs and symptoms that have been associated with TLS. This condition can progress rapidly; therefore, take any warning signs seriously and do not wait too long to seek treatment.2 Talk with your doctor and healthcare team, discuss the warning signs and symptoms, and identify the specific steps you should take if you suspect TLS. Locate your nearest emergency room and know whom to contact and when. Verify key contact information and keep important phone numbers with you.

If you develop TLS, you will need to be treated in a hospital. IV fluids and, in some cases, a diuretic will be given to increase hydration and urine output to quickly eliminate the damaging effects of the tumor cells from your body. Medication will be provided to reduce uric acid build-up. Once TLS has developed, rasburicase is the recommended medical therapy because it acts quickly and can break down uric acid that has already formed. However, allopurinol may be used if you have an allergy to rasburicase or G6PD deficiency.1

Throughout treatment, your electrolytes will be measured frequently and adjustments may be made to the IV fluids to restore electrolyte balance and prevent kidney damage/improve kidney function. In advanced cases, kidney dialysis may be required.1 Abnormal levels of potassium, phosphorus, and calcium also can affect the heart and nervous systems; therefore, you will be observed closely and may be put on a heart monitor.

Table 2. Warning Signs and Symptoms of TLS6,8

� Nausea

� Vomiting

� Diarrhea

� Shortness of breath

� Irregular heart beat

� Cloudy urine

� Decreased urine output

� Fatigue

� Joint discomfort

� Muscle weakness

� Muscle spasms/cramps

� Seizures

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ConclusionTLS is a rare, but serious condition. If you are preparing to start a new cancer treatment, you should discuss your particular risk for TLS with your doctor and heatlhcare team. With appropriate prevention strategies, use of medications to prevent accumulation of uric acid, and quick response to warning signs/symptoms, TLS is highly preventable and treatable.

Additional Resources:Leukemia & Lymphoma Society. Resources for patients with blood cancers, including the guide, “Understanding Side Effects of Drug Therapy.” Retreived from www.lls.org. Accessed 11/25/15.

References1. Jones GL, Will A, Jackson GH, et al. Guidelines for the management of TLS in

adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology. Br J Haematol. 2015;169(5):661-671.

2. Cairo MS, Coiffier B, Reiter A, Younes A. Recommendations for the evaluation of risk and prophylaxis of TLS in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578-586.

3. Seymour J, Roberts A, Stilgenbauer S, et al. Reduction of TLS risk in CLL patients treated with ABT-199 (GDC-0199): results of modifications to dosing schedule and TLS prophylaxis. European Hematology Association Congress; June 12-15, 2014; Milan, Italy.

4. Blumel S, Broadway-Duren J. Approaches to managing safety with lenalidomide in hematologic malignancies. J Adv Pract Oncol. 2014;5(4):269-279.

5. Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med. 2011;364(19):1844-1854.

6. Sarno J. Prevention and management of TLS in adults with malignancy. J Adv Pract Oncol. 2013;4(2):101-106.

7. Mirrakhimov AE, Voore P, Khan M, Ali AM. TLS: a clinical review. World J Crit Care Med. 2015;4(2):130-138.

8. Zelenetz AD, Gordon LI, Wierda WG, et al. Non-Hodgkin’s lymphomas, v4.2014. JNCCN. 2014;12(9):1282-1303.

What questions should I ask my doctor about TLS?

1. How common is TLS with the type of cancer I have and the therapy I am receiving?

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2. What steps can be taken to prevent TLS?

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3. Do I need to be aware of any dietary considerations to reduce my risk for TLS?

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4. Are there particular medications I should avoid to decrease my risk for TLS?

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5. What signs and symptoms should I watch out for?

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6. What signs and symptoms should I call you about?

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7. For which signs and symptoms should I go to an emergency room?

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8. If I do develop TLS, how will you treat it?

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9. What are the risks if I develop TLS and it does not get treated?

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10. Will I need to be hospitalized at the beginning of my cancer treatment so I can be monitored for TLS?

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11. (If you have existing kidney disease) What additional steps can be taken to address my kidney disease before starting cancer therapy to reduce the risk for TLS?

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12. What is the best way to contact you if I have questions?

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Print this page and take it with you when you meet your doctor.

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