WBR0158
Jump to navigation
Jump to search
| Author | [[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]] |
|---|---|
| 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 past medical history significant for gout on allopurinol, presents to her primary care physician for fatigue and weight loss. Complete blood count and peripheral smear reveal increased number of lymphoblasts. Bone marrow biopsy confirms the diagnosis of Acute Lymphoblastic Leukemia (ALL). Remission is induced with combination chemotherapy consisting of dexamethasone, vincristine, asparaginase, and daunorubicin. Repeat bone marrow biopsy later reveals residual disease that requires intensification therapy. Which of the following drugs should be avoided in this patient?]] |
| Answer A | AnswerA::5- fluorouracil |
| Answer A Explanation | [[AnswerAExp::5-Fluorouracil (5-FU) is a pyrimidine analogue that inhibits thymidylate synthase, an enzyme required for the de novo synthesis of thymidylate. It is indicated for several adenocarcinomas. 5-FU does not interact with allopurinol.]] |
| Answer B | AnswerB::6-mercaptopurine |
| Answer B Explanation | [[AnswerBExp::6-mercaptopurine (6-MP) is metabolized by xanthine oxidase, which is inhibited by allopurinol. Thus, co-administration of 6-MP and allopurinol may potentially lead to an increase in 6-MP blood levels and cause toxicity.]] |
| Answer C | AnswerC::6-thioguanine |
| Answer C Explanation | [[AnswerCExp::6-thioguanine (6-TG) is a guanine analogue antimetabolite. 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::Cytarabine is a competitive inhibitor of DNA polymerase. Upon entrance to the cell, cyatabine is converted to araCTP which is then incorporated into a growing strand of replicated DNA, resulting in elongation termination.]] |
| Answer E | AnswerE::Methotrexate |
| Answer E Explanation | [[AnswerEExp::Methotrexate is a folic acid analogue that inhibits dihydrofolate reductase, an enzyme responsible for the conversion of dihydrofolic acid to tetrahydrofolic acid (active form).]] |
| 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 at 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. Induction therapy in cases of adult ALL is generally by a combination of glucocorticoids (dexamethasone), vincristine, an anthracycline (usually daunorubicin), and asparaginase. ALL is typically highly responsive to chemotherapy. 6-mercaptopurine and 6-thioguanine are commonly used drugs for consolidation therapy, defined as treatment aimed at killing residual cancer cells. 6-MP is an inactive drug that is metabolized by xanthine oxidase, an enzyme located in the liver and the intestinal mucosa. In turn, allopurinol is a xanthine oxidase inhibitor, may decrease the metabolism of 6-MP. Thus, co-administration of 6-MP and allopurinol may lead to increased blood levels of 6-MP and cause toxicity, mainly leukopenia. Nonetheless, the combination of allopurinol and 6-MP may be clinically beneficial among patients with subtherapeutic concentrations of 6-MP. Co-administration of the 2 drugs with cautious monitoring has shown benefit when studied among patients with inflammatory bowel disease (IBD), cancer patients, and renal transplant recipients.
  Educational Objective: 6-mercaptopurine (6-MP) is metabolized by xanthine oxidase, an enzyme inhibited by allopurinol. Thus, co-administration of 6-MP and allopurinol may increase the blood concentration of 6-MP and lead to 6-MP-associated toxicity, such as leukopenia. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Cancer, WBRKeyword::Leukemia, WBRKeyword::ALL, WBRKeyword::Acute Lymphocytic Leukemia, WBRKeyword::Chemotherapy, WBRKeyword::Antimetabolite, WBRKeyword::Nucleotide |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |