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[Dr. Shapiro] This is Dr. Samantha Shapiro, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. And now, onto the episode.
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[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy.
[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine. Welcome to episode 106. Today's case is a 21-year-old with ALL. Right up your alley, Cathy. I think we're going to start with just the question. Ready?
[Dr. Handy] Yep.
[Dr. Wiener] Here we go. A 21-year-old man is treated with induction chemotherapy for acute lymphoblastic leukemia. His initial white blood cell count prior to treatment was 156,000. All of the following are expected complications during his treatment, except? So there's going to be four correct answers and one incorrect answer, okay?
[Dr. Handy] Okay.
[Dr. Wiener] Option A. is acute kidney injury; option B. is hypercalcemia; option C. is hyperkalemia; option D. is hyperphosphatemia; and option E. is hyperuricemia.
[Dr. Handy] I think what this question is getting at is tumor lysis syndrome and the complications related to that.
[Dr. Wiener] That's correct. Tell me more about tumor lysis syndrome.
[Dr. Handy] So tumor lysis syndrome occurs most commonly in individuals who are undergoing chemotherapy for rapidly proliferating malignancies, including acute leukemias, like in this patient. It's caused by the rapid destruction of tumor cells and the resultant release of intracellular ion and nucleic acids. There may also be activation of an inflammatory response. Now, as the chemotherapeutic agents act on these cells, there's massive tumor lysis that results in release of these intracellular ions and nucleic acids.
[Dr. Wiener] So the syndrome is a function of having a large tumor burden and the rapid killing effect of a chemotherapy agent, right?
[Dr. Handy] Exactly.
[Dr. Wiener] Okay, you mentioned the acute leukemias. So besides ALL and AML, what other malignancies should people think of as risks for tumor lysis?
[Dr. Handy] I'd also include on there non-Hodgkin's and Burkitt lymphoma, sometimes sarcomas, and rapidly growing solid tumors, such as small cell lung carcinoma. In rare instances, it can be seen with chronic lymphoma or other solid tumors as well.
[Dr. Wiener] Okay, now this question is not focusing on the cancer, it's mostly focusing on the metabolic complications of the treatment. So which are the typical complications?
[Dr. Handy] Yeah, so the release of intracellular contents leads to a characteristic metabolic syndrome, and what you get is hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia.
[Dr. Wiener] Okay, so that included choices C, D, and E, high potassium, high phosphate, and high uric acid levels are all characteristic. We'll talk about calcium in a second but what about the acute kidney injury? You didn't mention that at all.
[Dr. Handy] Yeah, so acute kidney injury can also result if uric acid crystallizes within the renal tubules. Plus, as I mentioned, there may be a systemic inflammatory response. So concomitant lactic acidosis and dehydration can increase the risk of acute kidney injury further.
[Dr. Wiener] So that means the answer's going to be B., hypercalcemia is not a part of this. What's the mechanism of that?
[Dr. Handy] So hyperphosphatemia, which occurs due to the release of intracellular phosphate ions causes a reciprocal reduction in serum calcium. So that's why you get hypocalcemia which can be profound, leading to neuromuscular irritability and even tetani.
[Dr. Wiener] Okay, and I'm going to assume that, you know, these patients are also overall sick, so any volume depletion or other metabolic dysfunction will precipitate or contribute to acute kidney injury.
[Dr. Handy] Yep. That can also contribute.
[Dr. Wiener] Okay. This is a two-part question day. So the first part of the question is that the answer was B., hypocalcemia, not hypercalcemia is an expected complication of what we identified as tumor lysis syndrome in this patient. So let's get to the second part which talks about treatment. The second question asks, in this patient, all of the following would be important for the prevention of the tumor lysis syndrome, except for? So there's going to be four correct answers again. So which one is incorrect? Option A. is administration of allopurinol; option B. is administration of IV fluids at a high rate; option C. is alkalization of the urine to get a pH of greater than 7 by administration of sodium bicarb; option D. is frequent monitoring of serum chemistries every four hours; or option E. is prophylactic hemodialysis prior to initiating chemotherapy.
[Dr. Handy] The answer to this question is E., prophylactic hemodialysis is not performed unless there's underlying renal failure prior to starting chemotherapy.
[Dr. Wiener] Okay, so that we know the other four are components of treatment of tumor lysis, let's run through those quickly.
[Dr. Handy] So it's important to monitor the serum electrolytes frequently during treatment. Laboratories should be obtained no less than three times daily but more frequent monitoring is often needed, especially early after the initiation of chemotherapy. Allopurinol to control uric acid should be administered prophylactically, if possible, before the initiation of chemotherapy and usually at high doses. And if allopurinol fails to control uric acid to less than 8 mg/dL, rasburicase, which is a recombinant urate oxidase can be added at a dose of 0.2 mg/kg. Throughout this period, the patient should be intravenously well-hydrated with alkalinization of the urine to a pH of greater than 7, and this lessens the risk of crystal development in the kidney.
[Dr. Wiener] So we covered a lot here. The teaching points, in this case, are that the tumor lysis syndrome occurs when there's rapid release of intracellular electrolytes due to a high tumor load and rapid killing from effective chemotherapy. The complications predominantly arise from the rapid increases in phosphate, potassium, and urate in the serum. In a susceptible patient, pre-treatment may be started with alkaline fluid administration and allopurinol combined with frequent monitoring of the serum electrolytes.
[Dr. Handy] And to learn more about this, you can read Harrison's chapter on oncologic emergencies.
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[Dr. Shapiro] Thanks for listening to Harrison's Podclass. You can listen to this episode and more on AccessMedicine.com, which includes the complete Harrison's Principles of Internal Medicine text, Harrison's review questions, which complement and expand upon the questions in this episode, and much more. AccessMedicine.com may already be available to you via your academic institution. Check it out.
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