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MKSAP: 58-year-old man is evaluated for increasing fatigue

mksap
Conditions
August 27, 2011
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Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 58-year-old man is evaluated for increasing fatigue of 2 months’ duration. The patient has hypertension and hyperlipidemia treated with lisinopril and atorvastatin. A sister has hypothyroidism.

On physical examination, temperature is normal, blood pressure is 135/80 mm Hg, pulse rate is 72/min, and respiration rate is 18/min. There is no lymphadenopathy or peripheral edema. The spleen is palpable 4 cm below the left costal margin.

Laboratory studies:

Hemoglobin 12.1 g/dL (121 g/L)
Leukocyte count 55,200/µL (55.2 × 109/L)
Platelet count 105,000/µL (105 × 109/L)

A peripheral blood smear shows an increased number of granulocytic cells in all phases of development but no Auer rods in the blasts. Bone marrow examination shows hypercellular marrow (80% cellularity) with marked granulocytic hyperplasia, a left shift in the granulocytes, and 3% myeloblasts. Cytogenetic testing reveals a BCR/ABL translocation.

Which of the following is the most appropriate next step in managing this patient?

A) Administration of imatinib
B) HLA typing of the patient and his sister
C) Leukapheresis
D) Observation with monthly follow-up office visits

MKSAP Answer and Critique

The correct answer is A) Administration of imatinib. This item is available to MKSAP 15 subscribers as item 8 in the General Hematology and Oncology section. More information about MKSAP 15 is available online.

This patient requires administration of imatinib. Chronic myeloid leukemia (CML) is the prototype of the myeloproliferative syndromes. It results from a balanced translocation between chromosomes 9 and 22 [t(9;22) the Philadelphia chromosome] creating a unique gene designated BCR-ABL, which codes a 210-kDa protein (p210) that functions as tyrosine kinase. The t(9;22) is not only diagnostic of CML, it is also the causative genetic event and a therapeutic target. The diagnosis of CML in this patient is based upon the presence of the BCR/ABL oncogene, peripheral blood smear findings showing increased granulocytes with a marked left shift and early erythrocyte precursors, and hypercellular bone marrow with marked myeloid proliferation. Patients with chronic-phase CML initially have less than 10% blasts in their bone marrow and peripheral blood. However, as the disease progresses, the blast count increases and is associated with an accelerated phase consisting of up to 20% blasts. A blast crisis may occur when the blast count is greater than 20%. Imatinib is a tyrosine kinase inhibitor that can lead to a complete cytogenetic remission in 70% of patients with CML and is most effective when used in the chronic phase of the disease. The optimal duration of therapy, long-term benefits, and toxicity of imatinib mesylate are under investigation. Imatinib has replaced hematopoietic stem cell transplantation (HSCT) as the initial treatment of patients with CML.

The best results for HSCT occur in patients with HLA-identical sibling donors. HSCT is curative for CML and was once the primary treatment option for patients with appropriately matched donors. However, HSCT is associated with significant morbidity and mortality and should be used only in very young patients with CML or in those who are resistant to the available tyrosine kinase inhibitors such as imatinib. Performing HLA typing in this patient and his sister to determine matching for HSCT is therefore not indicated at this time.

Leukapheresis is used to control the leukocytosis in patients with acute myeloid leukemia when the blast count is greater than 50,000/µL (50 × 109/L). Patients with acute myeloid leukemia may have an elevated leukocyte count, but most leukocytes are circulating myeloblasts, and the blasts may contain Auer rods (clumped lysozymes that appear as azurophilic cytoplasmic rods). Auer rods are not present in patients with CML.

Because treatment of patients with CML is most effective when initiated in the chronic phase, close observation is inappropriate at this time.

Key Point

  • Imatinib is a tyrosine kinase inhibitor that can lead to a complete cytogenetic remission in 70% of patients with chronic myeloid leukemia (CML); it is most effective when used in the chronic phase of CML.

Learn more about ACP’s MKSAP 15.

This content is excerpted from MKSAP 15 with permission from the American College of Physicians(ACP). Use is restricted in the same manner as that defined in the MKSAP 15 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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