Leukemia, Chronic Myelogenous (CML)

Key Features

• CML with translocation of chromosomes 9 and 22 (the Philadelphia chromosome, Ph+) is identical to adult Ph+CML

• Translocation 9;22 results in the fusion of the BCR gene on chromosome 22 and the ABL gene on chromosome 9

• The resulting fusion protein is a constitutively active tyrosine kinase that interacts with a variety of effector proteins and allows for deregulated cellular proliferation, decreased adherence of cells to the bone marrow extracellular matrix, and resistance to apoptosis

• The disease usually progresses within 3 years to an accelerated phase and then to a blast crisis

Clinical Findings

• Nonspecific complaints similar to those of acute leukemia may be present, including bone pain, fever, night sweats, and fatigue

• However, patients can also be asymptomatic

• Physical findings may include fever, pallor, ecchymoses, and hepatosplenomegaly

Diagnosis

• Patients with a total WBC count > 100,000/μL may have symptoms of leukostasis, such as dyspnea, priapism, or neurologic abnormalities

• Anemia, thrombocytosis, and leukocytosis are frequent laboratory findings

• The peripheral smear is usually diagnostic, with

  • Characteristic predominance of myeloid cells in all stages of maturation

  • Increased basophils

  • Relatively few blasts

Treatment

• Historically, hydroxyurea or busulfan has been used to reduce or eliminate Ph+ cells and hematopoietic stem cell transplantation was the only consistently curative intervention

• Imatinib mesylate

  • Tyrosine kinase inhibitor

  • Has had dramatic success, with most patients achieving cytogenetic remission

• Other tyrosine kinase inhibitors: dasatinib, erlotinib, nilotinib, and ponatinib

  • Durability of remission is unclear

  • Accepted upfront therapy