Leukemia: Diagnosis and Treatment

Diagnosis

Complete blood count with white blood cell (WBC) differential can give a presumptive diagnosis. For acute leukemias, the WBC count is usually >15,000 (and may exceed 100,000), with blast cells usually evident. However, a significant minority of patients will present with a decreased WBC count. Anemia and thrombocytopenia are usually present. Auer rods, azurophilic, rod-shaped inclusions in the cytoplasm of blasts, are almost diagnostic for AML.

The classic diagnosis for CLL requires an absolute lymphocyte count higher than 5,000 without another known cause for the lymphocytosis. Anemia or thrombocytopenia at presentation is correlated with a more aggressive clinical course.

In CML, the peripheral blood shows an increased WBC count with a significant left shift that includes cells usually seen only in the bone marrow. An increased number of basophils is almost always seen and can substantially predate an increase in WBCs. Thrombocytosis occurs in at least half of cases at presentation.

Bone marrow biopsy is often necessary for definitive diagnosis and staging. For CLL and CML, flow cytometry on peripheral blood can be diagnostic. For CML, polymerase chain reaction (PCR) on peripheral blood can demonstrate the presence of the Philadelphia chromosome.

Upon diagnosis, the following tests are typically indicated:

• Laboratory testing, which includes electrolytes, magnesium, phosphorous, renal function tests (blood urea nitrogen, creatinine), liver function tests (transaminases, alkaline phosphatase, bilirubin, lactate dehydrogenase), and coagulation studies (prothrombin time, partial thromboplastin time).
• Chest x-ray.
• HLA typing of the patient and siblings in potential transplant patients.
• Herpes simplex and cytomegalovirus serology.

Treatment

Acute leukemias are treated with chemotherapy, the goal being complete remission and cure of the disease. Stem cell transplantation is an option for some patients.

In CML, imatinib, a tyrosine kinase inhibitor, is currently the treatment of choice at diagnosis. Allogeneic stem cell transplant is appropriate (except in elderly patients) when imatinib cannot sustain a complete remission. Standard chemotherapy is currently used only in palliative efforts after progression.
 
Many patients with CLL can be observed without immediate treatment (up to one-third never require treatment). When initiated, treatment consists of chemotherapy and/or monoclonal antibody therapy. Allogeneic bone marrow transplantation is a potentially curative treatment for CLL in younger patients, but is not yet considered standard therapy. Radiation therapy may be indicated for palliation in patients with large, bulky masses that cause compression symptoms.