Chronic Myelogenous Leukemia
Chronic myelogenous leukemia (CML) is a slow-progressing leukemia associated with a specific genetic abnormality in the leukemia cell, called the Philadelphia chromosome. This abnormal gene is produced when genetic material called ABL is displaced from chromosome 9 and replaces the normal part of chromosome 22 next to a region called BCR. The resulting fusion gene, BCR/ABL, causes abnormal function of the ABL gene, which leads to the leukemia.
There are three main phases of CML:
- The disease almost always starts in the chronic phase, during which the disease is usually easy to control with treatment, and patients can lead nearly normal lives.
- The disease may progress over a few years into the accelerated phase. When this happens, the blood counts worsen and patients can experience high fever, bone pain and painful enlargement of the spleen.
- The blast phase of CML is a form of acute leukemia that is very difficult to treat. Two-thirds of the time it is myeloid, and is considered acute myeloid leukemia. One-third of the time, it is lymphoid (acute lymphoblastic leukemia, or ALL). Survival is usually only a matter of months once the blast phase occurs.
Our approach to chronic myelogenous leukemia
UCSF is dedicated to delivering the most advanced treatment options for chronic myelogenous leukemia (CML) with care and compassion. For most patients with early-stage CML, mainstay medications called tyrosine kinase inhibitors are effective in controlling the disease for many years, and they usually prevent it from progressing to the dangerous final phase. Should standard treatments fail, UCSF offers stem cell transplants as well as access to clinical trials of potential new therapies.
Awards & recognition
Among the top hospitals in the nation
Best in Northern California and No. 7 in the nation for cancer care
Signs & symptoms
Most patients with CML initially visit their doctor because of:
- Low-grade fevers or sweats
- Fullness in the abdomen caused by an enlarged spleen
Chronic myelogenous leukemia is generally suspected when tests reveal an elevated white blood cell count with immature "myeloid" cells in the blood.
The diagnosis is then confirmed by the presence of the Philadelphia chromosome, either by chromosome analysis, called cytogenetics, or by molecular testing for the abnormal BCR/ABL gene. A bone marrow biopsy helps determine whether the CML is in the chronic or advanced stage.
Tyrosine kinase inhibitors
The mainstay treatment for chronic phase CML is tyrosine kinase inhibitors (TKIs), such as imatinib (Gleevec), dasatinib (Sprycel) or nilotinib (Tasigna). TKIs are oral medications that shut down the abnormal protein produced by the BCR/ABL gene.
With TKIs, 80 percent of CML patients will have complete disappearance of the Philadelphia chromosome and restoration of normal blood counts. The life expectancy of chronic phase CML patients taking TKIs has improved from four to six years to well over a decade. In most patients, TKIs prevent conversion to the accelerated or blast phase. Dasatinib or nilotinib works for most patients who are resistant to imatinib.
Side effects of TKIs include rash, upset stomach, swelling of the eyelids, mild lowering of the blood counts and rare episodes of fluid build-up around the lungs and/or heart.
Patients survive a long time with TKIs, but it is still unknown if patients are cured by these drugs. The disease is monitored by a blood test for BCR/ABL every three months, and an annual bone marrow aspiration and biopsy.
Stem cell transplantation
The only proven cure for CML is allogeneic blood and marrow transplantation. Before TKIs were available, all chronic phase patients with tissue-matched donors received allogeneic transplantation. Cure rates were 70 to 80 percent. Because of treatment-related mortality of 15 to 20 percent, however, allogeneic transplantation is now reserved for patients failing TKIs.
UCSF is dedicated to improving outcomes of CML patients through the use of investigational therapies and clinical research trials. We currently have new TKIs and related drugs available to treat patients failing the approved TKIs. A world leader in understanding the mechanisms of BCR/ABL resistance to standard TKIs, Dr. Neil Shah, is at UCSF. His laboratory is developing new and better TKIs.
UCSF Health medical specialists have reviewed this information. It is for educational purposes only and is not intended to replace the advice of your doctor or other health care provider. We encourage you to discuss any questions or concerns you may have with your provider.