Experts James Short, MD, and John Reagan, MD, share comprehensive insight on the clinical implications of treating TLS in patients receiving therapy for cancer.
John L. Reagan, MD: Could you outline any of the clinical implications of prophylaxis and those treatment options within it—when you would do and when you wouldn’t do treatment for prophylaxis?
Nicholas James Short, MD: We can just think about some of the particular considerations that we have…I think using the IV fluids and the allopurinol are pretty clear for anyone who is intermediate or high-risk for tumor lysis syndrome. I think we’re not always sure when should we be using rasburicase. So, first of all, some considerations for rasburicase. This is what we’ve talked about, that this drug is very good at rapidly reducing uric acid levels. Typically, within 4 hours you can get a significant reduction of uric acid, just after 1 dose. Actually, 1 dose is often adequate for many patients. Although certainly there are patients with very aggressive, bulky tumors with rapid turnover, where you might need to redose. You might need to redose more than once. But in many cases, actually in my experience, 1 dose of rasburicase may be all a patient needs to get them out of the danger zone where you’re worried about clinical tumor lysis syndrome.
I think other considerations when we’re thinking about giving rasburicase, for example, is it’s very important after a patient has had rasburicase to accurately measure the uric acid. You need to measure it on ice. The sample should be transported on ice because if it’s not, the rasburicase will continue to dissolve like the uric acid in the sample and you’ll get a falsely low read. So, these are just some kind of clinical things to think about when you are treating a patient with rasburicase. Now, in general, it’s a well-tolerated drug, but hypersensitivity reactions can occur. So, you need to be aware of those. One of the main things to be aware of when giving a patient rasburicase is that you can see severe hemolysis in patients with G6PD [glucose-6-phosphate dehydrogenase] deficiency. That said, tumor lysis syndrome is an oncologic emergency and we often don’t have time to test for this. We often don’t know G6PD status on the majority of our patients. So, when you’re in that situation where a patient urgently needs to get the uric acid down, I don’t stop to test for this, but certainly if a patient has a known diagnosis of G6PD deficiency, you would not want to use rasburicase because of the risk for homolysis.
In thinking about who might be higher risk for G6PD deficiency, of note it is higher in those with ancestry from Africa, Asia, Mediterranean, or the Middle East. So, you might have a little more of a suspicion in those patients, and you need to be extra careful, of course, watching all of these patients. But I think the key thing is, at the very least, if you don’t have G6PD status before giving rasburicase, at least remember that hemolysis is a potential complication. If you start to see worsening anemia in the patients after the dose, you at least immediately think of this as a potential option and then treat accordingly.
Now, as far as when do we actually give the rasburicase prophylactically? Usually, based on the studies that you had mentioned, a lot of institutions have adopted a cutoff of around 7.5 mg of uric acid as kind of a threshold. But it’s not exactly just the uric acid in and of itself. For example, there are patients who have chronic kidney disease or other causes of hyperuricemia who have elevated uric acid. It doesn’t mean we should be giving rasburicase to those patients. The way at least we have it on our formulary and the way that we practice clinically, is we consider the level of the uric acid. So again, a cutoff of 7.5 mg is often helpful. For those patients, even who have a uric acid of 7.5 mg or higher, they have to have at least 2 other risk factors to justify giving the rasburicase.
Also, this goes along with, do I really think that this is related tumor lysis syndrome, or could it just be from something else? So, those would include patients who have an elevated serum creatinine. Those patients who have a very high white blood cell count of 50,000 or higher, an elevated LDH [lactate dehydrogenase], or they have underlying high-risk disease. Like we mentioned, [that includes], very aggressive B-cell lymphoma or an aggressive acute leukemia. Now, even for those patients who have lower uric acid levels, below 7.5 mg, we still do consider it prophylactically even for those patients if they have multiple of those risk factors. If I have a patient with Burkitt leukemia or lymphoma who has an elevated LDH and a high white blood cell count and their uric acid is 7, I’m still definitely going to give that patient rasburicase before I start treatment because I’m almost certain that that patient is going to develop tumor lysis syndrome if I don’t.
Other considerations for rasburicase that are important to think about—interestingly, allopurinol and rasburicase, even though they’re both used for treatment or prevention of tumor lysis syndrome, they actually can be a little antagonistic, at least theoretically. Allopurinol can actually interfere with rasburicase activity. If possible, we like to give rasburicase first if we’re planning to do that, and then start the allopurinol afterwards. Now, this is not always feasible, unfortunately. A patient may come in and they may have already been on allopurinol, or they started allopurinol as prevention and then they start to develop tumor lysis syndrome. We often then just add the rasburicase on top of it but acknowledge that that may not be as effective as if you give the rasburicase in someone who hasn’t been exposed to allopurinol. So, ideally you give rasburicase and then start the allopurinol afterwards.
In thinking about how we’re doing all this management, hopefully we can manage all these electrolyte abnormalities and other issues, but sometimes it does come down to getting our nephrology colleagues involved. The next step after giving hydration, allopurinol, rasburicase, and all the measures that we discussed earlier, sometimes dialysis is really the only thing that’s going to clear out those electrolytes, protect the kidneys or support the kidneys through this event. It’s really just supportive care, but we typically only reserve this for patients after all of our other supportive care measures that I mentioned have not worked.
Transcript edited for clarity.