This article could save your life even if you are NOT on treatment yet.

Did your doctor mention the possibility of TLS or high uric acid associated with your treatment? You need to know that TLS is an emergency.

Fortunately this is uncommon in patients who are not being treated. The more cancer cells you have in lymph nodes or blood the more likely this is to occur, especially during treatment. As explained below TLS can usually be prevented or treated with fluids and medicines like allopurinol.

Blood Cancer Uncensored is honoured to have been selected as a partner site to the CLL Pharmacist, and is delighted to welcome their founder Tom Henry as one of our authors.

Join him as he explains what we all should look out for to save a life in this abridged version of an article you can also read in full.

When I started on ibrutinib, my CLL specialist started me on allopurinol, to reduce the risk of TLS, and when I later started venetoclax I actually experienced mild TLS.

1. What is Tumor Lysis Syndrome?

Tumor lysis syndrome (TLS) is an emergency situation that can occur in patients with cancer. TLS happens when cancer cells die quickly, either as a result of treatment or in rare cases when the patient’s own immune system attacks the cancer, resulting in rapid cell death. 

When cancer cells die, they essentially rupture or “lyse”, which results in the release of large amounts of potassium, phosphate and uric acid into the blood.

When these chemicals are released into the bloodstream the body’s organs can become overwhelmed resulting in a variety of problems including renal dysfunction, cardiac arrhythmias, seizures, or other neurologic complications and even death.

TLS should never be taken lightly. A major concern for patients is that it can quickly sneak up on you and can become life-threatening, especially if it is not recognized, managed, or treated properly.

TLS occurs most commonly in patients with blood cancers, such as chronic lymphocytic leukemia (CLL), who are receiving cytotoxic (cell-killing) therapies that kill the rapidly dividing cancer cells. TLS can occur in as little as a few hours after treatment starts, but is usually seen in the first 2-3 days after treatment begins. 

Before starting any treatment you should ask your physician if TLS is a risk.

2. TLS an Emergency – Risks

TLS occurs most frequently in blood cancers such as leukemias (including CLL) and lymphomas (including small lymphocytic lymphoma or SLL).

Historically, TLS has been associated with cytotoxic treatments such as traditional chemotherapy (e.g. fludarabine, cyclophosphamide, and rituximab (FCR) or bendamustine and rituximab (BR). The most commonly used novel targeted agents for CLL can also cause TLS as a potential adverse effect including:

• Ibrutinib (Imbruvica®) 
• Acalabrutinib (Calquence®)
• Venetoclax (Venclexta®) [Very high potential]
• Lenalidomide (Revlimid®) 

This doesn’t mean other targeted CLL drugs cannot cause TLS, but it is less common.

Other treatments can also cause TLS in cancer patients including, traditional chemotherapy, steroids, hormonal therapy, and radiation therapy. The common factor regardless is rapid cell death.

3. TLS an Emergency –

There are two steps your physician will recommend to decrease and, hopefully eliminate the chance that TLS occurs.

A. The first step is hydration which is key to success! If we hydrate before treatment, we keep fluid moving through the kidneys, so they can filter the increased electrolytes (potassium, phosphorus, and uric acid), we mentioned earlier. Hydration also helps keep the blood from becoming acidic (acidosis) which reduces the risk of uric acid crystals forming in the blood that can lead to kidney damage and painful gout-like symptoms of pain and inflammation in joints, particularly the joints of the hands and feet.

Typical hydration orders for inpatients are 4750-5700mL/day for a man or 4000-4800mL per day for a woman. Just to put these numbers in perspective, for a man that is 20-24 glasses of water.

Most of the current CLL oral therapies are usually started in the outpatient setting, (with the possible exception of venetoclax) and the recommendation is 60 to 70 ounces of water a day or 1,800 to 2400mL a day.

Some physicians start venetoclax patients on an inpatient basis, especially if the patient has a high tumor burden (lots of swollen lymph nodes and possibly spleen or liver enlargement) so that they can push the higher volumes used in the inpatient setting.

The goal of hydration is to increase urine output, and dilute the electrolytes released by TLS.

Key Verses

Observations

What it first meant

What it means to us

First Step. The second prevention step is drug prophylaxis (prevention). Three drugs are commonly used allopurinol, febuxostat, and rasburicase to minimize hyperuricemia (high uric acid in the blood) and prevent the formation of uric acid crystals.

Rasburicase is rarely used to prevent hyperuricemia because it is extremely expensive but it works really well for patients with pre-existing high uric acid levels or renal dysfunction prior to starting treatment. This drug is most often used when uric acid levels do not respond to the other agents.

Tumor Lysis Syndrome is a potentially life-threatening condition. Do you know what to look for?

4. What are the Signs and Symptoms of TLS?

You should be suspicious of TLS, if you experience sudden onset of any of the following:

• fatigue or confusion
• nausea, vomiting or diarrhea
• muscle weakness, cramps or spasms
• tingling around the mouth or in your hands or feet
• a feeling that your heart flutters, or beats faster or slower than normal, or
• seizures.

5. When Should I Seek Immediate Care or Call 9-1-1?

Remember, TLS is a medical emergency. You should seek immediate medical care if you experience any of these symptoms:

• you have a seizure and are not normally a seizure patient
• you feel an abnormal heartbeat and this is a new problem
• you have a sudden onset of tingling around the mouth or in your hands or Him
• you have new issues with muscle weakness, cramwife ps or spasms
• you are abnormally fatigued or confused
• you have blood in your urine, or
• you urinate less than normal (for you) or not at all.

Final Thoughts

Tumor Lysis Syndrome (TLS) can occur as a result of treatment, for your CLL, or even spontaneously. The chances of you being affected are significantly reduced if your medical team recognizes which treatments and which patients are more prone to this condition and take the necessary steps ahead of beginning therapy. It is common for patients to start TLS prophylactic drugs a day or two before starting therapy.

You can be better prepared to discuss this condition with your provider if you know what to look for and what questions to ask your team. Always remember TLS is an emergency in CLL.

Research has shown that patients who have a CLL Specialist as part of their team live longer and have better outcomes. CLL Specialists are among the best prepared to prevent TLS, recognize it when it occurs an rapidly treat if it occurs.  

CLLPharmacist.com – Directory of CLL Specialists

We want you to know where to find a CLL Specialist. Our list contains more than 300 names of physicians who don’t just do research but see patients. Our directory includes specialists who practice medicine in 23 countries. Download our list here.