Several options now exist for the treatment of chronic myelogenous leukemia (CML). At Memorial Sloan Kettering, which approach our physicians recommend for you will depend on a number of factors:
- the stage of the disease
- whether you have already received treatment elsewhere
- what treatments you received, and how successful they were
- the number of blasts in the bone marrow
- the results of chromosome testing
- your overall health and any other medical problems you might be facing
Treatment for Chronic Phase CML
Three drugs are now available for treating CML in its chronic phase. All three work by blocking the activity of BCR/ABL, the abnormal protein found in CML. Although none of these drugs is a cure, they can dramatically improve the lives of people with the disease and, in most cases, can help to manage it for years.
Your doctor may recommend imatinib (Gleevec™) as initial therapy for CML. Imatinib was the first drug discovered to be capable of controlling CML, and a very high percentage of patients in the chronic phase of the disease respond positively to it. Typically, patients' complete blood count normalizes within the first three months of treatment, and the number of cells that contain the Philadelphia chromosome decreases.
Although imatinib is effective at controlling CML in most patients, a very small number experience adverse side effects. In addition, over time, some patients become resistant to imatinib when the BCR/ABL protein mutates and imatinib can no longer interact with it.
If you do not respond positively to upfront imatinib, you may receive one of two newer drugs called dasatinib (Sprycel™) or nilotinib (Tasigna™). In some cases, your physician may recommend one of these medications as upfront treatment. Less is known about these drugs than imatinib, although two recent studies suggest that compared to imatinib, dasatinib and nilotinib may be more efficient in clearing the bone marrow of leukemia cells, and may work faster.(1),(2)
In some instances, one drug may be recommended over the other if you have problems with your lungs or heart. During treatment with any of these three medications, patients are monitored frequently to assess their response and to check for side effects.
Stem Cell Transplantation
In some patients, CML can become unresponsive to imatinib and other drugs. When this occurs, another option is stem cell transplantation.
In this procedure, called an allogeneic transplantation, blood-forming stem cells are removed from another person whose blood is closely matched to the patient's. The patient then receives a high dose of chemotherapy, sometimes in conjunction with radiation therapy, which destroys tumor cells. This process also damages stem cells in the bone marrow, breaking down the patient's immune system. Harvested stem cells from the donor are then given (transplanted) to the patient to help rebuild his or her immune system.
Memorial Sloan Kettering has one of the longest-standing and most experienced stem cell transplantation programs in the United States. Learn more about stem cell transplantation at Memorial Sloan Kettering.
Treatment for Accelerated Phase CML
If your disease is in the accelerated phase, treatment may include the options outlined above — imatinib, dasatinib, nilotinib, and bone marrow transplantation. If you have CML that does not respond positively to imatinib, dasatinib, or nilotinib, your doctor may also suggest immunotherapy (a drug called interferon) or chemotherapy. Patients may also receive transfusions of blood or blood products to relieve symptoms.
Treatment for Blast Phase CML
If your disease is in the blast phase, treatment is likely to include chemotherapy in addition to imatinib, dasatinib, or nilotinib. This is a difficult phase of the disease to treat. Often, stem cell transplantation is recommended if an appropriate donor is available and you are healthy enough to undergo the procedure.
Because the best results with stem cell transplantation occur when CML is in the chronic or early accelerated phase, the goal of treatment during the blast phase is to first get the patient back to an earlier phase of the disease before transplantation takes place.
Researchers are now developing new agents for cancer treatment at a faster rate than at any time since chemotherapeutic drugs were introduced in the late 1940s. Relying, in part, on information that is emerging about the genetic basis of leukemia, investigators are pursuing a variety of strategies to control the disease — approaches that can kill tumor cells directly, inhibit the body's production of substances that promote their growth, or enhance the immune response against leukemic cells.
Below are some of the therapies now being tested for CML. Studies of these and other promising new treatments are available to patients through clinical trials. For patients whose disease has recurred or is resistant to standard treatments, or who are not candidates for stem cell transplantation, clinical trials provide additional treatment options.
Researchers are studying the most-effective ways to use the targeted therapies that are now available (imatinib, dasatinib, and nilotinib). This includes determining the best timing and dosage. We are also working to create and test additional therapies that will block variants of the mutated BCR/ABL gene.
Many leukemias, including CML, as well as some solid tumors are associated with chromosome translocations that create fusion genes — new genes that include pieces of two original chromosomes. These new genes contain instructions for new proteins, called fusion gene products. Researchers are using the amino acid sequences of these fusion proteins or mutated sequences to develop tumor-specific vaccines (called oncogene fusion point vaccines) for treating patients with cancer.
The first such vaccine for treating CML was developed by investigators at Memorial Sloan Kettering and has been used in clinical trials to treat patients. The vaccine consists of a piece of the protein made by the Philadelphia chromosome gene and uses a portion of the fusion gene, called the BCR/ABL fusion point, as its target. The goal of this therapeutic vaccine is to make the patient's immune system recognize and destroy the leukemia cells.
Cellular Therapy after Stem Cell Transplantation
Following a stem cell transplantation for CML, some patients experience a recurrence of the disease. A strategy developed here at Memorial Sloan Kettering and at other institutions — a reinfusion of a particular type of white blood cell called lymphocytes from the original stem cell donor — may boost these patients' ability to fight the disease. The effectiveness of this approach is now under study.