A 54-year old Caucasian man comes to the office complaining of fatigue, poor exercise tolerance, and an unexplained weight loss over the last 6 months. He does not use tobacco, alcohol, or drugs. His family history is noncontributory. He takes no medications. His vital signs are within normal limits. Examination reveals mild splenomegaly but no lymphadenopathy. Laboratory tests show the following:
Cytogenetic testing reveals a bcr/abl translocation. Which of the following is the best initial treatment option for this patient?

Question

A 54-year old Caucasian man comes to the office complaining of fatigue, poor exercise tolerance, and an unexplained weight loss over the last 6 months.  He does not use tobacco, alcohol, or drugs.  His family history is noncontributory.  He takes no medications.  His vital signs are within normal limits.  Examination reveals mild splenomegaly but no lymphadenopathy.  Laboratory tests show the following:
 Cytogenetic testing reveals a bcr/abl translocation.  Which of the following is the best initial treatment option for this patient?

Quizplus · Accepted Answer

Explanation: The most likely diagnosis in this case is chronic myeloid leukemia (CML). This patient's nonspecific symptoms of fatigue, poor exercise tolerance, and weight loss are fairly typical. Splenomegaly is also fairly common, with some patients experiencing left upper abdominal discomfort or early satiety. Up to 50% of patients are asymptomatic, with disease-related abnormalities detected on routine blood tests performed for another reason. The diagnosis should be suspected in patients with a markedly elevated WBC count. The diagnosis is usually confirmed by genetic testing for the presence of the Philadelphia chromosome, which results from a translocation of chromosomes 9 and 22. This particular chromosome translocation results in production of a bcr/abl fusion protein that causes unregulated stimulation of the tyrosine kinase system. Thus, tyrosine kinase inhibitors are the treatment of choice. Even though these agents do not cure the disease, they can bring about good long term disease control. Because of this almost all CML patients are initially treated with these agents. (Choice A) Tyrosine kinase agents are more routinely used in CML treatment than alkylating chemotherapy. (Choice B) Bone marrow transplant (BMT) can offer potential cure in CML. However, it has a much higher morbidity and mortality compared with tyrosine kinase inhibitors. BMT can be offered to patients who are young with stable disease and who have a suitable donor. (Choice C) Leukapheresis would only be considered if the patient had symptoms of hyperviscosity syndrome with a WBC count on the order of 400,000/mm³. Educational objective: Chronic myeloid leukemia (CML) is caused by a translocation of chromosomes 9 and 22, which produces the Philadelphia chromosome. The presence of the bcr/abl fusion protein is diagnostic of CML and results in unregulated tyrosine kinase activity. Tyrosine kinase inhibitors such as imatinib are the initial treatment of choice in almost all instances. Later, BMT can be offered to patients who are young with stable disease and who have a suitable donor.

A 54-Year Old Caucasian Man Comes to the Office Complaining