Q: I read your column about CLL a couple of weeks ago. My mom has CML, not CLL. Is this very different?

Q: I read your column about CLL a couple of weeks ago. My mom has CML, not CLL. Is this very different?


A: Although chronic myelogenous leukemia (CML) affects a different type of cell than chronic lymphocytic leukemia (CLL), there are many similarities between them. However, there are also many important differences.


Both CML and CLL are chronic (slowly progressive) leukemias (cancers of the bone marrow and blood) that affect certain types of white blood cells. Both are most commonly diagnosed while they are not causing any symptoms, typically because of elevated white blood cell counts noted when a blood test is done for other reasons or for an annual evaluation. Both may have more specialized testing done to determine the genetic details of the affected cells.


As with CLL, the symptoms and complications from CML often arise from the "crowding out" and, hence, decreased production of normally functioning cells in the bone marrow, and include anemia, bleeding problems and infections.


CLL, which is newly diagnosed in about 15,000 Americans a year, is more common than CML, which is newly diagnosed in about 4,800 Americans per year. Both are more common in people older than 55, and are slightly more common in men than women.


From the work of doctors Nowell and Hungerford done in 1960 in Philadelphia, CML was the first cancer to be shown to be due to a certain type of defect that develops in the genes (translocation of chromosome 9 and 21 leading to formation of the abnormal bcr-abl gene).


Because of this, the genetic mutation responsible for CML is called the Philadelphia chromosome. This defect causes the leukemic cells to overproduce the protein tyrosine kinase, which in turn promotes the cancerous growth of the abnormal cells. This defect occurs spontaneously (it is not hereditary), and is more frequent in people exposed to radiation or certain chemicals (such as benzene).


Similar to CLL, the extent of disease in CML patients is "staged." Very immature blood cells called "blasts" do not normally appear in the blood; the amount of these cells is used to stage CML. Less than 10 percent blast cells define the chronic stage of CML, and 80 percent of patients are diagnosed in this stage.


The accelerated stage is defined by blast counts between 10 percent and 20 percent, or other criteria such as very low or very high platelet counts, an enlarged spleen, or progression of the disease despite treatment.


Finally, the blast stage - similar to acute leukemia with aggressive progression of disease and a very poor prognosis if not treated - is defined by over 20 percent blasts.


Unlike CLL, untreated CML typically transforms to the more advanced stages within three to five years. Therefore, CML is usually treated as soon as it is diagnosed.


Just a few decades ago, there were no effective treatments for CML. However, there has been tremendous improvement in the treatment of this disease, including the use of immune system proteins (interferon), certain chemotherapy medications and, most importantly, development of drugs that specifically target the bcr-abl gene.


In 2001, the FDA approved imatinib mesylate (Gleevec), the first medication of this type, although since then others have been developed.


The bcr-abl blockers do not cure CML, so treatment with these medications must be continued. However, they have greatly improved the prognosis for CML patients, with five-year survival rates now more than 90 percent. The newer bcr-abl blockers are usually used for patients who do not respond to, or develop side effects from, imatinib, although studies are under way to see if they are as good as, or better than, imatinib.


Stem cell transplantation, for people healthy enough to tolerate it, offers the possibility of a cure for CML patients.


Although there are many similarities between CML and CLL, the differences are extremely important. Specifically, CLL may stay in a non-aggressive state for up to a decade or more, but CML typically transforms to an aggressive disease within three to five years. Therefore, early treatment for CML is usually recommended.


The insight into the genetics of CML has led to developed treatments that specifically target the abnormal genes in the leukemic cells. These treatments have tremendously improved the prognosis for people with CML, and there is hope that even more progress will be made in the future.


Jeff Hersh, Ph.D., M.D., F.A.A.P., F.A.C.P., F.A.A.E.P., can be reached at DrHersh@juno.com.