Chemotherapy
Nearly all CML patients are diagnosed when in the chronic phase of the disease. The chronic phase of the disease can usually be controlled by drugs (chemotherapy). Table 1 lists some of the drugs used to treat the chronic phase of the disease. Currently, alpha-interferon is used most frequently.

Table 1.

In this phase, the blood counts return to normal and can be maintained at or near normal levels. The spleen decreases toward normal size. Infections and abnormal bleeding are unusual.

Patients can resume their previous, day-to-day activities. However, they will need to receive frequent treatments and periodic checks of their health status and blood counts. Much less frequently, they will need to have marrow examinations.

The use of interferon is associated with flu-like side effects: fever, muscle aches, and weakness. In some patients, prolonged fatigue and weight loss may require reduction in doses administered. Hair loss, diarrhea, depression, ulceration of the lining of the mouth, cardiac effects, and others, are side effects that occasionally occur and may require changes in treatment approaches.

Other Special Treatments

Stem Cell Transplantation
Stem cell transplantation is an important form of therapy for CML patients who have an HLA-matched donor. This therapy was formerly referred to as Bone Marrow Transplantation, but now is more often referred to as stem cell transplantation. At the present time, stem cell transplantation is the only curative form of treatment for chronic myelogenous leukemia.

In stem cell transplantation, the blood as well as marrow is a source of stem cells. This approach requires a tissue-type (HLA) matched donor (related or unrelated), and is most successful in younger patients. HLA-matched related donors usually are a brother or sister. An unrelated donor is usually identified by searching the National Marrow Donor Program database.

The decisions on the utilization and timing of transplantation are complex. One reason for this is that chemotherapy is now more successful, resulting in a median duration of remission of about six years or more. The patient's age, the genetic compatibility of the prospective donor, and the degree of the response to drug therapy in the first months of treatment must be carefully assessed to reach a decision about using transplantation.

Autologous Stem Cell Infusion
Only a small proportion of patients have the key combination of an HLA-matched donor and younger age that makes allogeneic transplantation feasible. Thus, therapists are studying the use of the patient's own marrow or blood as a source of stem cells for transplantation. This treatment option is known as autologous stem cell infusion. Marrow or blood stem cells are frozen during the chronic phase of the disease, and later used to treat patients who have entered the accelerated phase of the disease. The hope for this procedure is that restoring the chronic phase will lengthen life and lessen symptoms.

The marrow and blood of patients with chronic myelogenous leukemia have small proportions of normal stem cells. Residual leukemia cells may also be present that were collected with the marrow or blood, and reinfused during transplant. In an effort to eliminate the leukemia cells, and collect the normal cells to use for the autologous stem cell treatment, many centers are using a technique known as "purging." Chemicals have been developed that selectively cleanse the marrow of leukemia cells, and thereby enrich the normal stem cells. In patients who have a dramatic decrease in leukemic (Ph-chromosome positive) cells during treatment of the chronic phase, blood or marrow can be harvested and frozen for later use, if necessary. Other techniques are also being studied to enable physicians to treat patients with intensive therapy, and subsequently restore marrow function by returning normal stem cells harvested from the patient.

Leukapheresis
Some patients may have extraordinary increases in their blood white cell counts. This can impair blood flow to the brain, lungs, eyes, and other sites. Patients can be treated initially with the removal of white cells by a machine that is similar to a dialysis machine. The process is called leukapheresis ("leuk" from the Greek for white (cells) and "apheresis" from the Greek for "withdrawal"). Hydroxyurea, a drug that can decrease the white cell count, is often used as well. After the white cell count has been decreased, interferon therapy can be instituted.

Leukapheresis can be used if the disease occurs during the first months of pregnancy when chemotherapy may be harmful to fetal development.

Acute Transformation of the Chronic Phase of CML

In most CML patients, the chronic phase of the disease transforms into a phase that becomes more difficult to manage and more troublesome for the patient. This second phase is called the "accelerated phase." During the accelerated phase, the numbers of white blood cells and immature or "blast cells" in the bloodstream increase.

Ultimately, the transformation may closely resemble acute leukemia. This is referred to as the "blast phase." During this phase, the immature or leukemic blast cells dominate the marrow and blood. This phase is usually resistant to chemotherapy. More aggressive treatment, involving drugs used in the treatment of acute leukemia, is applied. In about one-quarter of patients, the transformation takes on the appearance of acute lymphocytic leukemia rather than acute myelogenous leukemia. Somewhat different drugs are used to treat the acute lymphocytic leukemia transformation.

In some cases, stem cell transplantation may be used in this more advanced phase of the disease. Stem cell transplantation is less successful in the accelerated or leukemic phase, but it can produce remissions in some patients.

Other Related Diseases

Chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia are disorders that are similar to chronic myelogenous leukemia. In general, they create more severe disturbances in blood cell counts early in the disease, and these disturbances are not as well controlled with current drug treatments. These disorders do not have the Ph-chromosome or the BCR-ABL mutation, and this difference is one of several distinguishing features used in their diagnosis. Chronic neutrophilic leukemia is another very uncommon disease, which is different from chronic myelogenous leukemia in its manifestations, behavior, and response to therapy.

Social and Emotional Aspects

The diagnosis of leukemia may provoke a profound emotional response in the patient, family members, and friends. Denial, depression, a feeling of hopelessness, and fear are normal and usual reactions. No one response is either expected or unexpected.

A lack of understanding of what's in store, the unknown, and what's next should be met by thoughtful, straightforward, and frequent discussions among physician, nurse, patient, and family. An inability to work, tend to business affairs, or interact with family and friends in the usual manner may contribute to emotional distress. Thorough explanations, including the prospects for remission and the plans for treatment, may bring emotional relief as the patient focuses on the treatment ahead and the prospect of recovery.

Children may feel frightened and helpless and may be too young to fully understand the nature of the problem. They may direct their anger and fear of being hurt toward medical staff. Reengagement in as many activities as possible is one of the best ways to soothe and reassure the child and minimize disruptions in the child's development.

Parents of children with leukemia may be confused, angry, and fearful. Time commitments and financial burdens of the illness may cause disagreements within the family. Siblings of the patient may also be affected. They may fear the disease will strike them. They may feel guilty that something they did or said caused their brother's or sister's illness. They may feel guilty that they are healthy and their sibling is ill. They may receive less time from parents who must devote extra time to their ill child.

Family members or loved ones may have questions about chemotherapy and alternative methods of treatment. It is best to speak directly with physicians regarding specific medical questions. Family members or loved ones should discuss any problems or reactions they may have. Nurses and other health professionals understand the complexity of emotions and the special ongoing needs of those living with leukemia. They also will spend much time with patients, becoming their confidants, and can be very helpful in their emotional support. For more information about the social and emotional aspects of the disease, you may request a copy of the following Leukemia Society publication: Coping With Survival, a booklet dealing with the psychosocial aspects of the disease for leukemia patients.

There are programs to help ease the emotional and economic strain created by leukemia. The Leukemia Society offers patients financial assistance, the opportunity to join a support group, or talk with a successfully treated patient with the same diagnosis.

To order publications or obtain information about programs, call your local LSA chapter or call the public information resource line at (800) 955-4LSA. You may also want to visit our website at www.leukemia.org to view publications and obtain more information about the Leukemia Society programs and services.

Follow-Up

Patients who are in remission continue to be examined regularly by their physicians. Careful periodic assessment of the patient's state of health, blood cell counts, and, if necessary, marrow is required. As time progresses, the interval between assessments may be lengthened but should be continued indefinitely.

The Future

Important advances have been made in the treatment of chronic myelogenous leukemia. Areas of research that have contributed to this progress include treatment with alpha interferon and stem cell transplantation, using sibling or unrelated HLA-matched donors.

Studies are currently under way to learn if combining alpha-interferon with other drugs, such as cytarabine, can lead to further improvements in the treatment of the chronic phase of the disease.

Improved techniques of matching unrelated donors by analysis of DNA should make unrelated donor transplantation more successful.

Clinical investigators are treating relapsed marrow transplant patients with infusions of donor white blood cells that suppress the growth of leukemia cells. The aim of these investigations is to develop new ways of using normal immune cells to attack the leukemia cells.

The discovery of the oncogene (BCR-ABL) and the oncoprotein, the product of the abnormal gene that initiates chronic myelogenous leukemia, may make it possible to intrude on the leukemia-causing process with new chemicals called "antisense" agents. In theory, these agents specifically interfere with the oncogene that directs the formation of the oncoprotein. The oncoprotein causes the development of chronic myelogenous leukemia. The antisense agents can, consequently, induce the leukemia cells to die. Early studies hold hope that such an approach can complement or replace current therapy.

These and other new approaches, many of which are being supported by the research programs of the Leukemia Society of America, hold the promise of increasing the rate of remission and cure of leukemia.

The Leukemia Society would like to acknowledge Marshall A. Lichtman, M.D. who contributed the material presented in this booklet.

As of yet this material is used without permission