Identification of Tumor Lysis Syndrome: Signs and Symptoms


Comprehensive insight on the signs and symptoms that help lead to the identification of tumor lysis syndrome in patients receiving therapy for cancer.


Nicholas James Short, MD: Talk about some of the signs and symptoms. What are we looking for in a patient undergoing treatment to see if they have tumor lysis syndrome [TLS]?

John L. Reagan, MD: A lot of these data came out in the 1990s, when we had more effective chemotherapies initially for tumor lysis syndrome. As you pointed out, some of it is how aggressive the tumor is, but then a lot of it is how effective your treatment is. Another thing, at least with tumors and tumor type, is that a lot of times it depends on your tumor bulk. Especially if you have bone marrow involvement, that can be another source of tumor lysis. When you have an infiltrated marrow from a leukemia which is thought to be 1.4 kg overall or if you have a marrow with over 50% blasts, that’s a patient who could also end up with tumor lysis.

The signs that you see are typically divided into 2 categories. There’s a laboratory tumor lysis syndrome, and then there are clinical criteria for tumor lysis syndrome. You probably see the laboratory criteria pretty often. When patients come in, this is something that helps you stratify who has to be admitted and watched. This is the first classification to come out, and the 1 we more commonly use. There’s a classification that happened before this, but the Cairo-Bishop [criteria] is probably the 1 that people are most familiar with. This looked at different markers of elevated uric acid levels, elevated phosphorus levels, elevated potassium, and low calcium levels.

What you’re looking for from a laboratory tumor lysis syndrome with Cairo-Bishop was uric acid more than 8 mg/dL, a phosphorus level of more than 4.5 mg/dL, a potassium level that’s over 6 mmol/L, and a correcting calcium level of less than 7 mg/dL. It’s so hard to get corrected calcium levels. Often, you’ll use an ionized calcium of less than 4.5 mg/dL. Cairo-Bishop added that if you had a 25% change from your baseline levels, that also classified you. Suddenly, if your uric acid level went up, this could become a sign of laboratory tumor lysis. I probably find that 1 most useful with your uric acid because you’ll see uric acids start to climb up a little when you have someone admitted, or you’re following them as an outpatient for some signs or symptoms of tumor lysis.

The updated Howard criteria—this was modified Cairo-Bishop criteria—removed that 25% change from baseline levels. Your laboratory levels were strictly: uric acid more than 8 mg/dL, phosphate greater than 4.5 mg/dL, potassium greater than 6 mmol/L, and the corrected calcium less than 7 mg/dL. That change was taken out—make it a little more clinically available. These levels, importantly, should happen 3 days before or 7 days after the initial initiation of a cancer directed therapy.

Added to that are any clinical criteria for tumor lysis, and these are the ones that are much scarier. The clinical criteria are cardiac dysrhythmia, or sudden death. That’s something that you can’t modify in any way, shape, or form. That could be caused by hyperkalemia. That can also be caused by hypocalcemia developing. For hypocalcemia, when those clinical signs will be a Chvostek sign, in which you tap on the side of the face and get fasciculations within the cheek.

But the 1 that we see most often in any of these is the elevation of a serum creatinine. Initially, Cairo-Bishop was more than 1.5 times the upper limit of normal for your serum creatinine, and the modified Howard did an increase in your serum creatinine above 0.3 mg/dL if you had that greater than 1.5 times the upper limit normal in terms of your serum creatinine. Once again, it’s important to understand what your patient’s baseline serum creatinine is going in and how they’re going to adequately deal with any volume shifts or release of these intracellular electrolytes and nucleic acids.

With a lot of these, both of the laboratory [criteria are used] you really want to avoid these clinical manifestations of tumor lysis syndrome. I don’t know if you have any other thoughts on that, Nick. Do you want to delve into the members of the care team, how they’re involved in monitoring and management of TLS, and what specific roles you see with each member of these teams?

Nicholas James Short, MD: You covered most of it. It’s 1 of those things where there are a lot of numbers, and it’s important. For example, at our institution [The University of Texas MD Anderson Cancer Center], we have some available algorithms because these things are complicated. As you mentioned, there’s a lot of numbers in terms of whether it meets formal criteria of tumor lysis syndrome. Those are definitely very helpful as guidance. As I said, you can pull up and plug things in and ask, does this look like real tumor lysis syndrome? It’s 1 of those things that, because you’ve treated patients with this for a while, you get a general idea and don’t necessarily have to look at those numbers. The general principle is that you’re going to see potentially elevations of potassium and phosphorus, eventually low calcium, along with an elevated uric acid. As you mentioned, the effect on the renal function is 1 of the most important things because that’s where you go from a laboratory tumor lysis to a more clinical 1. That’s where it’s more important to intervene or do additional preventive measures.

Transcript edited for clarity.

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