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 investigational treatment with tumor-targeting T-cells. Approximately two weeks after receiving the injection, the patient develops a fever of 40 °C (104 °F) with chills and generalized erythema. 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 |
| Answer A | AnswerA::Hydrochlorothiazide |
| Answer A Explanation | AnswerAExp::Hydrochlorathiazide is not particularly helpful in this patient, considering that large doses of thiazide diuretics increase uric acid retention. |
| Answer B | AnswerB::Furosemide |
| Answer B Explanation | AnswerBExp::Patients with normal renal and cardiac function do not require diuretics necessarily; however, furosemide use is preferred in TLS patients because it causes further renal secretion of potassium after filtration. |
| 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 most likely explanation is the activation of the administered anti-tumor T-cells and release of copious amounts cytokines such as IL-6 (cytokine storm). Patients with cytokine storm present with high grade fever, erythema, and elevated levels of TNF-alpha, IL-1, and IL-6. At the same time, the patient's lab demonstrate signs of tumor lysis syndrome secondary to rapid destruction of tumor cells. TLS is caused by the breakdown products of dying cancer cells and is characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and hyperuricosuria 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. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Tumor, WBRKeyword::Tumor lysis, WBRKeyword::Tumor lysis syndrome, WBRKeyword::Uric acid, WBRKeyword::Cancer, WBRKeyword::Oncology, WBRKeyword::Chemotherapy |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |