WBR0943

Author	PageAuthor::William J Gibson (Reviewed by Serge Korjian)
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Oncology, SubCategory::Renal
Prompt	[[Prompt::A 72-year-old man with end-stage Chronic Lymphocytic Leukemia is administered an experimental treatment with tumor-targeting T-cells. Approximately two weeks after receiving the injection, the patient develops a fever of 104 F with shaking and chills. Laboratory studies reveal a thousand-fold increase in IL-6 along with the results shown below. Which of the following is the most appropriate pharmacotherapy in this patient? Sodium: 140 mEq/L Potassium: 5.5 mm/L Phosphate: 5.0 mg/dL Calcium: 8.0 mg/dL Uric acid: 16.0 mg/dL (Normal 2.0 – 8.0) Lactic Acid: 5.0 mEq/L (Normal 0.7-2.1) ]]
Answer A	AnswerA::Hydrochlorothiazide
Answer A Explanation	[[AnswerAExp::Hydrochlorathiazide may be potentially dangerous in this patient. Tumor lysis syndrome causes the release of large amount of intracellular Potassium into the circulation. Thiazide diuretics increase renal reabsorption of potassium and may thereby exacerbate hyperkalemia.]]
Answer B	AnswerB::Furosemide
Answer B Explanation	[[AnswerBExp::Furosemide use is encouraged in TLS patients with reduced cardiac or renal function in order to help increase urine flow and clear uric acid from the body. Furosemide is also a preferred diuretic in tumor lysis syndrome because it increases the renal secretion of potassium. However, furosemide treatment is less essential than administration of allopurinol or rasburicase.]]
Answer C	AnswerC::Corticosteroids
Answer C Explanation	AnswerCExp::Corticosteroids are often used for treatment of leukemias, and may help to decrease the intensity of the anti-tumor response in this patient but they are not first-line agents for tumor lysis syndrome.
Answer D	AnswerD::Allopurinol
Answer D Explanation	[[AnswerDExp::Allopurinol is a xanthine oxidase inhibitor that decreases the production of uric acid; it is essential in the treatment of tumor lysis syndrome. Tumor lysis syndrome is associated with the release of large amounts of uric acid from ruptured tumor cells. This uric acid can precipitate in the renal tubules, causing acute kidney injury.]]
Answer E	AnswerE::Acetazolamide
Answer E Explanation	AnswerEExp::While alkalinization of the urine can help to solubilize uric acid, the clinical data to support the use of acetazolamide in tumor lysis syndrome are weak. It is much more important to decrease the formation of uric acid with allopurinol.
Right Answer	RightAnswer::D
Explanation	[[Explanation::The patient in this vignette has a combination of cytokine storm and tumor lysis syndrome (TLS). The anti-tumor T-cells have become activated multiplied and are releasing copious cytokines such as IL6 (cytokine storm). At the same time, the tumor cells are being rapidly destroyed leading to tumor lysis syndrome. TLS is caused by the breakdown products of dying cancer cells and includes hyperkalemia, hyperphosphatemia, hyperuricemia and hyperuricosuria, hypocalcemia, leading to consequent acute uric acid nephropathy and acute kidney injury. Treatment of tumor lysis syndrome consists primarily of managing uric acid levels and electrolytes. In all cases of suspected TLS, patients should receive IV hydration. When TLS is confirmed, patients should receive allopurinol or in more serious cases, rasburicase (a recombinant enzyme that degrades uric acid). In severe cases, patients must be started on hemodialysis. Educational Objective: Allopurinol is a xanthine oxidase inhibitor that decreases the production of uric acid; it is essential in the treatment of tumor lysis syndrome. References: ]]
Approved	Approved::Yes
Keyword	WBRKeyword::Tumor, WBRKeyword::Tumor lysis, WBRKeyword::Tumor lysis syndrome, WBRKeyword::Uric acid, WBRKeyword::Cancer, WBRKeyword::Oncology, WBRKeyword::Chemotherapy
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