Expert perspectives on prophylactic measures to prevent tumor lysis syndrome in patients receiving therapy for cancer.
John L. Reagan, MD: How do you think about prophylaxing these patients to prevent tumor lysis from happening in the first place?
Nicholas James Short, MD: First, what you said is so important. Theoretically, we have all the tools necessary to manage tumor lysis syndrome, but preventing it is so important. If you’re going for curative therapy and you have to pause to manage all these acute issues coming up—many of which are, at least theoretically, preventable—then that’s where the detriment to the patient may come. Not so much the tumor lysis itself, which hopefully we can manage; it will just be a transient process. But if we have to hold back on appropriate therapy for a patient, then that’s problematic. That’s very important what you discussed.
How do we prevent? First, we do need to think about risk stratification. Going back to risk factors, we don’t necessarily do the same prevention methods for everyone. For someone we consider relatively low risk for tumor lysis syndrome, like a solid tumor, nothing in particular is done. But if they’re in an intermediate risk, we have certain strategies that we do. High risk would be a little different.
Generally speaking, for anyone who’s in intermediate or high risk, we’re certainly doing hydration. Hydration is important to prevent that potential renal damage, which is what causes most of the complications. You’ll have renal dysfunction and also further buildup of electrolytes if your kidneys aren’t functioning properly. The hydration just flushes the kidneys out, preventing the buildup. Potentially, there are urate crystals, which come from the uric acid or the calcium phosphate crystals. That’s an integral part of prevention.
Some patients can’t tolerate large amounts of IV [intravenous] hydration. Maybe they have an underlying cardiomyopathy [or something else]. In those patients, diuretics can play a role because you can still give the fluids, but then you counterbalance that with diuretics. Historically people would give diuretics no matter what. Maybe people practice a little differently, but as long as someone isn’t developing fluid overload, I just hydrate. I do diuretics only if I’m concerned that I’m causing fluid overload. I don’t necessarily want to back off my hydration, but diuretics can be important to make sure you’re maintaining good ins and outs and fluid balance as you’re trying to prevent development of tumor lysis.
Of the electrolyte issues you mentioned before, particularly the elevated potassium and phosphorus, we want patients to limit this from their diet, particularly if they’re high risk or already developing tumor lysis syndrome. We want to limit potassium phosphorus intake if possible. Even when someone is initially starting on therapy, if we’re worried that they might be a little high risk for tumor lysis syndrome, we might not be as aggressive at repleting the low potassium and phosphorus as we might be in someone who we didn’t have any concern for tumor lysis.
One of the backbones of all those preventives are agents that affect uric acid levels. For anybody who’s intermediate or high risk, we’d add allopurinol. Allopurinol helps prevent uric acid buildup, but it doesn’t do anything for the uric acid that’s already there. That’s where we consider using rasburicase. Rasburicase we use for high-risk patients. Sometimes it’s a preventive measure, and sometimes we use it also for patients who’ve already developed tumor lysis. It’s very effective at rapidly dropping uric acid levels.
There are some things we don’t necessarily do prophylactically, and it’s on the border of whether you consider this in a patient who already has tumor lysis, but sometimes [we use] phosphate binders. Usually we wait to see if the phosphorus is becoming elevated, [and that’s] where we consider adding phosphate binders. Then there’s dialysis. At my institution [The University of Texas MD Anderson Cancer Center], and it differs. If you have a very high-risk patient, like 1 with a Burkitt lymphoma, who already has evidence of some clinical lysis syndrome, we may not start dialysis right away, but we’d involve our nephrology colleagues and say, “This patient is very high risk.” We’re not necessarily saying we’re going to start dialysis preventively, but we want to watch very carefully and we want to be ready. The last thing you want is to not be ready if a patient develops flora renal failure, and then you’re scrambling to do these things.
Those are all the considerations that we have when we’re starting a patient on therapy or a patient comes in with a new diagnosis of 1 of these hematologic malignancies. We want to risk-stratify them. Fluids and allopurinol are going to be the case for most patients with intermediate risk, then plus or minus rasburicase. I know we’ll be talking about the criteria that might be used, including evidence-based studies to support that.
Transcript edited for clarity.