Cancer | Leukemia | Chronic Myelogenous Leukemia

Chronic myelogenous leukemia (CML) is a chronic leukemia associated with a specific genetic abnormality in the leukemia cell called the Philadelphia chromosome, T9 or 22. This abnormal gene is produced when genetic material called ABL is displaced from chromosome 9 and then replaces the normal part of chromosome 22 next to a region called BCR. The resulting fusion gene BCRABL causes abnormal function of the ABL gene, which leads to the leukemia.

Most patients with CML initially visit their doctor because of:

There are three main phases of CML:

Chronic myelogenous leukemia (CML) is generally suspected after finding of 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 BCRABL gene. A bone marrow biopsy helps determine whether the CML is in an early or advanced stage.

In the past, without bone marrow transplantation, the average survival for patients with chronic myelogenous leukemia (CML) was four to six years. While some patients will progress and die quickly, some can live for longer than 10 years, depending on their tolerance for certain drugs.

The outlook of allogeneic transplantation depends on a number of factors. For example, young patients with matched sibling donors who get their transplants during the first year after their diagnosis have a 70 to 80 percent chance of being cured.

The first step of treatment uses the chemotherapy drug hydroxyurea to control the disease. Hydroxyurea is a gentle oral chemotherapy drug with few side effects. It reduces the white blood cell count, shrinks the spleen and reduces or eliminates symptoms of the disease. However, this treatment does not affect a patient's long-term outcome.

The only known curative treatment for CML is an allogeneic stem cell transplant, also called a bone marrow transplant. Although this is a difficult and dangerous procedure, it is usually recommended within the first year of diagnosis if the patient is relatively healthy, under age sixty and has a suitable stem cell or bone marrow donor. When allogeneic transplantation is performed early in the chronic phase, a patient's chance of long-term survival and probable cure rate is 70 percent to 80 percent. If the transplant is performed later than the first year, results are about 50 percent to 60 percent. The disadvantage of transplantation is that approximately 15 percent of patients will die of treatment-related complications during the first six months. However, waiting for the disease to advance is also a problem, since long-term survival drops to 30 percent if transplantation is performed in the accelerated phase, and falls to 10 percent or less if performed in the blast phase.

For younger patients who do not have a matched sibling donor, it is appropriate to search for a matched unrelated donor through the National Marrow Donor Program (NMDP). This type of allogeneic transplant is more difficult and dangerous than transplant using a sibling donor. In the past, the treatment-related mortality of this procedure had been 40 percent with long-term survival at 40 percent to 60 percent. However, newer and better methods of matching may lead to better results, especially in young patients (under age thirty-five) transplanted in the first year of their disease.

For patients with CML who are not candidates for transplantation, the current standard treatment is to use interferon, which can be given alone but works slightly better when combined with cytarabine (ARA-C). Interferon treatment can result in controlled blood counts (called hematologic remission) and can reduce the percentage of bone marrow cells that contain the Philadelphia chromosome (cytogenetic remission). Although it is not curative treatment, interferon, compared to hydroxyurea, has been shown to prolong survival with CML.

STI-571 is a promising new experimental drug being tested for CML, and it was designed specifically to act against the product of the Philadelphia chromosome. It is given by mouth and has relatively few side effects. Preliminary results are very encouraging, both in the chronic and more-advanced phases of the disease. Although it is not likely to cure the disease on its own, it is highly likely that STI-571 will play a major role in the treatment of CML. At this time, it is available only in research studies.

A new variation of allogeneic transplantation, called the "mini allogeneic" transplant, may have a major impact on the outcome of CML. This experimental procedure is less difficult and dangerous than a standard transplant. It can be used in people who are not good candidates for standard transplant because of their age or general health. Although preliminary results are very encouraging, it remains to be seen if the long-term outcomes are as good as with standard transplants.