WBR0158

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Hematology, SubCategory::Oncology
Prompt	[[Prompt::A 76-year-old woman with a history of gout adequately controlled with allopurinol presents to her primary care physician for fatigue. Complete blood count reveals marked neutropenia. Bone marrow biopsy confirms the diagnosis of Acute Lymphoblastic Leukemia. Remission is induced with combination chemotherapy consisting of dexamethasone, vincristine, asparaginase, and daunorubicin. Repeat bone marrow biopsy later reveals residual disease, requiring intensification therapy. Which of the following drugs should be avoided in this patient?]]
Answer A	AnswerA::5- Fluorouracil
Answer A Explanation	[[AnswerAExp::Incorrect: 5-Fluorouracil (5-FU) is a pyrimidine analogue that inhibits thymidylate synthase. It is indicated for the treatment of a variety of adenocarcinomas and does not interact with allopurinol.]]
Answer B	AnswerB::6-Mercaptopurine
Answer B Explanation	[[AnswerBExp::Correct: 6-Mercaptopurine (6-MP) is metabolized by xanthine oxidase, the target of allopurinol. Thus, coadministration of 6-MP and allopurinol can lead to overdose of 6-MP and toxicity.]]
Answer C	AnswerC::6-Thioguanine
Answer C Explanation	[[AnswerCExp::Incorrect: 6-Thioguanine (6-TG) is an antimetabolite guanine analogue. 6-TG is converted to 6-thioguanine monophosphate by HGPRT. It inhibits DNA synthesis in a similar manner to 6-MP. However, 6-TG is safe to administer with allopurinol.]]
Answer D	AnswerD::Cytarabine
Answer D Explanation	[[AnswerDExp::Incorrect: Cytarabine is a competitive inhibitor of DNA polymerase. Upon entrance to the cell, cyatabine is converted to araCTP which can then be incorporated into a growing strand of replicated DNA, resulting in elongation termination.]]
Answer E	AnswerE::Methotrexate
Answer E Explanation	[[AnswerEExp::Incorrect: Methotrexate competitively inhibits folic acid binding to Dihydrofolate reductase, an enzyme responsible for the conversion of dihydrofolic acid to the activate form, tetrahydrofolic acid. Tetrathydrofolic acid is an essential substrate for the synthesis of thymidylate, which is in turn required for DNA synthesis.]]
Right Answer	RightAnswer::B
Explanation	[[Explanation::Acute lymphoblastic leukemia (ALL) is a hematopoetic malignancy characterized by replacement of the bone marrow by lymphoblastic cells similar to the cells pictured below. ALL is most common in childhood with a peak incidence at 2–5 years of age, and another peak in old age. Immunohistochemical analysis of tumor biopsies may reveal TdT or CALLA antigens on the surface of leukemic cells. TdT is a protein expressed early in the development of pre-T and pre-B cells, whereas CALLA is an antigen found in 80% of ALL cases and also in the "blast crisis" of CML. ALL is typically highly responsive to chemotherapy. 6-Mercaptopurine and 6-thioguanine are commonly used drugs for consolidation therapy in these patients. 6-MP is metabolized by xanthine oxidase, the target of allopurinol. Thus, co-administration of 6-MP and allopurinol can lead to overdose of 6-MP and toxicity. Bone marrow biopsy of patient with ALL Peripheral blood smear of patient with ALL Educational Objective: 6-Mercaptopurine (6-MP) is metabolized by xanthine oxidase, the target of allopurinol. Thus, coadministration of 6-MP and allopurinol can lead to overdose of 6-MP and toxicity. References: First Aid 2012 page 399 Educational Objective: References: ]]
Approved	Approved::Yes
Keyword	WBRKeyword::Cancer, WBRKeyword::Leukemia, WBRKeyword::ALL, WBRKeyword::Acute Lymphocytic Leukemia, WBRKeyword::Chemotherapy, WBRKeyword::Antimetabolite, WBRKeyword::Nucleotide
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