Accelerated Phase

This content has been reviewed and approved by

Hagop M. Kantarjian, MD
Chairman & Professor, Leukemia Department
MD Anderson Cancer Center
University of Texas

Chronic myeloid leukemia (CML) normally progresses from the chronic phase to an accelerated phase and ultimately into a blastic or acute leukemia phase over a period of several years. Some patients, however, will be in the accelerated phase at the time of initial diagnosis.

The diagnosis of accelerated phase requires at least one of the following:

• Persistent presence of 10 to 30 percent myeloblasts in marrow or peripheral blood
• Major increase of white blood cell count to more than 50,000
• Platelet counts that are increased or decreased
• Red blood cell levels that are low despite treatment
• Progressive enlargement of the spleen
• Tumor nodules outside the bone marrow or spleen
• Any abnormal chromosome in addition to the Philadelphia chromosome
• Persistent unexplained fever or bone pain
  

Once the criteria for accelerated phase are met, the average survival of patients with CML is less than 18 months. Patients may progress to the accelerated phase of CML without experiencing any symptoms. The diagnosis can be made on the basis of peripheral blood or bone marrow findings only.

When CML progresses to the accelerated phase, the leukemia cells may look like either myeloid or lymphoid cells and generally respond poorly to treatment. Until recently, intensive chemotherapy regimens designed for the treatment of acute myeloid leukemia were used, and 25 percent to 35 percent of patients in accelerated phase achieved a remission of relatively short duration. In 2001, Gleevec^® (imatinib mesylate) was approved for the treatment of accelerated and blastic phase CML.

Treatment of Accelerated Phase CML

Many of the treatments in accelerated phase are similar to those discussed under chronic phase. Imatinib remains the standard of care if allogeneic transplant is not possible.

In the accelerated phase, allogeneic stem cell transplantation should be considered as a serious first-line option.

Other strategies include:

• Combinations of imatinib plus interferon plus ara-C
• Imatinib plus chemotherapy
• High-dose imatinib
• Dasatinib
• Other tyrosine kinase inhibitors
• Investigational drugs (e.g., homoharringtonine, decitabine, etc.)

Allogeneic stem cell transplantation - Selected patients in the accelerated phase who are treated with high-dose chemotherapy and allogeneic stem cell transplant (using stem cells from a related donor) have a 5-year survival rate of up to 45 percent. Patients transplanted in the blastic phase have a 5-year survival rate of approximately 15 percent. There has been significant recent progress in the selection of compatible unrelated stem cell donors. Patients with accelerated phase CML transplanted from an HLA-compatible unrelated donor have a 20 percent to 40 percent probability of 5-year survival, while patients in the blast phase have approximately a 10 percent probability of 5-year survival.