Chronic Myelogenous Leukemia (CML) is a malignant disorder of hematopoiesis resulting from expansion of a primitive hematopoietic cell. This malignant stem cell retains the capacity to differentiate which leads to marked marrow hyperplasia and increased numbers of myeloid cells and platelets in the peripheral blood. This was the first malignant disease3 to be associated with a specific cytogenetic abnormality, the Philadelphia (Ph) chromosome. The advent of the tyrosine kinase inhibitor (TKI) imatinib mesylate (Gleevec) has changed the landscape of CML therapy and has moved transplantation from up-front therapy of choice to an option as salvage therapy.
CML represents about 14% of all new leukemia cases in the United States, with an annual incidence of 1.6 cases per 100,000. The median age at diagnosis is 67 years, but a small number of CML patients are children. Exposure to ionizing radiation (e.g. survivors of the atomic bomb) is the only known risk factor.
There are three phases of CML – Chronic phase, Accelerated phase, Blast crisis.
Chronic phase (CP) – most CML patients (90%) present in CP and symptoms, when present, include fatigue, weight loss, bony aches and abdominal discomfort from enlarged spleen. Patients have markedly elevated white blood count, elevated platelet count and low red blood cell count (anemia). Bone marrow is hypercellular (i.e. too many blood cells). Cytogenetic examination shows the presence of the Ph chromosome in >90% of patients. Without therapy, CML CP evolves to Accelerated Phase.
Accelerated phase (AP) – various definitions of AP have been developed, but in general AP is characterized by symptoms of fever, night sweats, weight loss, and bone pain. There is difficulty controlling blood counts using conventional therapy and increased numbers of blasts (immature white blood cells).
Blast crisis (BC) has been defined as having more than 30% blasts in the bone marrow or peripheral blood. Approximately two-thirds of patients will have blasts that atre myeloid, while the remaining one-third have blasts of lymphoid type.
A blood or marrow transplant is the only known cure for CML. Transplant is only used if other drugs, specifically TKI drugs, stop working or cause too many severe symptoms. Allogeneic transplants, usually matched sibling donor or unrelated donor, are used for CML. There are medical guidelines for when an individual should be referred for transplantation consultation. In general, talking with a transplant doctor is recommended for CML when the disease does not get better after treatment with TKIs, when the patient has serious side effects from the TKI therapy, when there is disease progression to accelerated phase or blast crisis.