A 62-year-old woman comes to the office due to a painless neck mass that has gradually enlarged over several months. She also has had fatigue, night sweats, and unintentional weight loss. Physical examination shows rubbery, nontender, bilateral cervical lymphadenopathy. Imaging studies reveal mediastinal and abdominal lymphadenopathy, and subsequent excisional lymph node biopsy is consistent with diffuse large B cell lymphoma. The patient receives combination chemotherapy, which leads to rapid lysis of neoplastic cells. She also receives rasburicase prior to and during treatment. This medication helps to protect normal organs by which of the following mechanisms?

Question

A 62-year-old woman comes to the office due to a painless neck mass that has gradually enlarged over several months.  She also has had fatigue, night sweats, and unintentional weight loss.  Physical examination shows rubbery, nontender, bilateral cervical lymphadenopathy.  Imaging studies reveal mediastinal and abdominal lymphadenopathy, and subsequent excisional lymph node biopsy is consistent with diffuse large B cell lymphoma.  The patient receives combination chemotherapy, which leads to rapid lysis of neoplastic cells.  She also receives rasburicase prior to and during treatment.  This medication helps to protect normal organs by which of the following mechanisms?

Quizplus · Accepted Answer

11ec160b_3bea_d617_9249_058907c23939_MD0001_00 Tumor lysis syndrome (TLS) is an oncologic emergency that primarily develops during initial chemotherapy for high-grade lymphomas, leukemias, and other cancers with rapid cell turnover, substantial tumor burden, or high sensitivity to chemotherapy. When large numbers of tumor cells are destroyed in a short period, massive quantities of intracellular tumor products are released into the circulation, which frequently results in the following: Hyperkalemia, which can cause fatal heart arrhythmias. Hyperphosphatemia, which precipitates calcium in the renal tubules and collecting system, leading to systemic hypocalcemia and acute renal injury from calcium-phosphate stones. Hyperuricemia, which precipitates urate crystals in the renal tubules and collecting system, leading to acute renal injury. Aggressive intravenous fluids during and after chemotherapy can help prevent kidney injury by flushing phosphorous and uric acid out of the kidneys. Treatment with an agent that reduces the formation of uric acid is also generally required to limit the formation of uric acid stones, including 1 of the following: Rasburicase is a recombinant version of urate oxidase, an enzyme present in many mammals, but not in humans. Urate oxidase converts uric acid into allantoin, a purine metabolite that is 5-10 times more soluble than uric acid and therefore far less likely to precipitate in the kidney. Allopurinol is a purine decoy that competitively inhibits xanthine oxidase (and other enzymes involved in purine metabolism), which reduces the conversion of purine metabolites into xanthine and uric acid (Choice C). Febuxostat is a non-purine selective inhibitor of xanthine oxidase; it is similar to allopurinol, but it has fewer adverse effects and drug interactions. (Choice B) Phosphate binders (eg, sevelamer) are used to manage hyperphosphatemia in patients with chronic kidney disease. Rasburicase does not target phosphate. (Choice D) Mesna can prevent hemorrhagic cystitis in patients receiving cyclophosphamide or ifosfamide; it supplies a thiol group that inactivates the toxic metabolite (acrolein) of these chemotherapeutic agents. (Choice E) Folinic acid (leucovorin) provides a reduced form of folic acid to counter the methotrexate-induced block in folic acid metabolism. It "rescues" gastrointestinal mucosa and bone marrow cells from the effects of methotrexate (which causes cell death in rapidly dividing cells). Educational objective: Tumor lysis syndrome primarily develops during chemotherapy for cancers with rapid cell turnover, substantial tumor burden, or high sensitivity to chemotherapy. It is characterized by hyperphosphatemia, hypocalcemia, hyperkalemia, and hyperuricemia. Prevention involves intravenous fluids to flush the kidneys and the use of hypouricemic agents (eg, rasburicase, allopurinol, febuxostat). __________ References: Rasburicase for the treatment of tumor lysis in hematological malignancies. (http://www.ncbi.nlm.nih.gov/pubmed/22272702)

A 62-Year-Old Woman Comes to the Office Due to a Painless