Chronic Myeloid Leukemia

Treatment Options

Scientific research has led to several treatment options for CML over the past two decades. And, through clinical trials, researchers are looking for ways to improve current treatments as well as learn more about this blood cancer. To develop the most appropriate disease management plan for you, your doctor will take into consideration the phase of the CML, the presence of chromosome abnormalities and your general health.

Once your diagnosis is confirmed, consider working closely with a hematologist or oncologist who specializes in treating people with CML. Together you can discuss the goals of treatment, which will vary depending on the phase of CML (see Table 1), potential side effects of treatment, supportive care and your expectations.

Table 1 - Goals of Treatment

Phase Goal
Chronic Phase Reduce symptoms of CML
Eliminate cells containing BCR-ABL1 gene
Achieve complete cytogenetic response
Remission
Prevent disease progression
Accelerated Phase Eliminate cells containing BCR-ABL1 gene
Prevent disease progression
Return CML to Chronic phase
Remission
Blast phase Control CML until a bone marrow transplant an occur
Remission

Along with your doctor, you may also work with a team of health care professionals who are experts in different specialties. This multi-disciplinary team may include oncology nurses, social workers, pharmacists, counselors, dietitians, financial counselors and others.

CML Therapies Defined

Standard of care refers to a diagnostic and treatment process that a clinician is recommended to follow for a certain type of patient and illness. In general, treatment may be considered first line or second line. First-line therapy is the first treatment given. Second-line therapy is given when the first-line therapy doesn’t work, is no longer effective or is not well-tolerated.

Treatments may be local or systemic. Local treatments are directed to a specific organ or limited area of the body. For CML, this may include surgery to remove the spleen (splenectomy) if it becomes too enlarged. Systemic treatments travel throughout your body and are typically drug therapies such as targeted therapy, immunotherapy or chemotherapy.

Your initial treatment strategy will be based on several factors, including the phase of your CML (chronic, accelerated or blast), risk group, personal preferences, age and overall health.

Some doctors further categorize CML into risk groups. Risk groups (low, intermediate and high) may be used to plan treatment and predict prognosis (outcome).

Three scoring systems may be used to determine your risk group (see Table 2):

  • Sokal score is based on age, spleen size, platelet counts and percent of blasts.
  • Hasford score is based on age, spleen size, platelet counts and percent of blasts, eosinophils and basophils.
  • EUTOS score is based on spleen size and percent of basophils.

Table 2 - Risk Groups


Risk Group Scoring System
Low Sokal score: less than 0.8
Hasford score: 780 or less
EUTOS long-term survival score: 1.5680 or less
Intermediate Sokal score: between 0.8 and 1.2
Hasford score: between 781 and 1480
EUTOS long-term surival score: between 1.5680 and 2.2185
High Sokal score: more than 1.2
Hasford score: more than 1480
EUTOS long-term survival score: more than 2.2185

Your doctor may recommend one or more of the following types of treatment.

Targeted therapy uses drugs or other substances to identify and attack specific cancer cells, and may also target genes, proteins or tissue around the cancer that support it. Some targeted therapy drugs are oral medications given in pill form, and others are given intravenously (IV).

Targeted therapy, given orally in pill form, is often the first line of treatment for chronic phase CML. More advanced stages of CML will usually respond temporarily but quickly require additional treatment; however, some patients in the chronic phase can receive targeted therapy and remain in remission for many years.

Targeted therapies treat many cancer types. For CML, they target the BCR-ABL tyrosine kinase enzyme. The Philadelphia chromosome creates the BCR-ABL1 protein (also known as a tyrosine kinase). Kinases are a type of enzyme that speeds up chemical reactions in the body. The Philadelphia chromosome causes an overgrowth of this abnormal kinase. Tyrosine kinase inhibitors (TKIs) are used to block the action of the abnormal kinase created by the Philadelphia chromosome. This approach is designed to prevent CML cells from growing.

Several TKIs are approved for treating CML and each works slightly differently. Some are specifically approved for newly diagnosed patients, while others are approved for use after other therapies have failed due to resistance, changes in mutations or intolerance.

Sometimes TKIs stop working, which is known as resistance. If resistance to a targeted therapy develops, other TKIs may work. The response to the TKI therapy (complete response, partial response or no response) can be monitored by a blood test.

If you and your doctor choose a TKI as part of your disease management plan, it is important to share with your doctor any supplements, vitamins, over-the-counter drugs, herbs or other medications you take because of the risk of a drug interaction. Ask your doctor about the supplements known to interfere with TKIs. Also, tell your doctor if you take antacids, heart medicine or anti-depressants.

To help you keep track of your medications, download a free medication tracking sheet.

Stem cell transplantation can restore your body’s ability to produce blood cells. Another name for a stem cell transplant is a hematopoietic transplant. There are two types of stem cell transplants: autologous (one that uses your own stem cells) and allogeneic (one that uses donor stem cells). Only an allogeneic (“allo”) stem cell transplant is used for patients with CML. It may be recommended when the disease is in the accelerated or blast phase.

A stem cell donor for an allo transplant may be found through a national or international registry. To ensure the donor tissue matches yours as closely as possible, human leukocyte antigen (HLA) matching is performed before a donor stem cell transplant. HLAs are molecules found on the surface of most cells in the body. HLA antigens make up a person’s tissue type, which varies from person to person. They play an important part in the body’s immune response to foreign substances. Blood and tissue samples are used to test for HLAs. Your HLA type will be compared to the donor’s HLA type to see how closely you match. Doctors look for the highest match so that your body does not reject the donor’s cells, nor do the donor’s cells attack you.

This potentially serious condition is called Graft-versus-Host Disease (GvHD). The donated cells see your tissues as foreign and attack them. It is more common in older patients or when using a donor who is not related to you, especially if the donor is not a complete match. Symptoms of GvHD include a skin rash, and stomach, liver, lung or muscle problems.

Stem cell transplants generally occur as follows:

  1. Stem cell collection. A medical professional collects, filters and processes stem cells from a donor. In some cases, the cells are frozen and stored for use later.
  2. Conditioning. You receive high-dose chemotherapy and/or full-body radiation therapy to destroy the cancer cells and to suppress your immune system so that you will not reject the donor’s cells.
  3. Stem cell transfusion. A doctor injects the harvested stem cells into your body intravenously (IV).
  4. Recovery and engraftment. Generally, within about 30 days, healthy cells begin to grow (engraft). Until your weakened immune system recovers, you will be at risk for infection. You may receive antibiotics and other drug therapy in the hospital and at home. Your doctor will monitor your numbers of different blood cells until they are back to safe levels.

Donor lymphocyte infusion (DLI) is a type of therapy in which lymphocytes (a type of white blood cell) from the blood of a donor are given to a patient who has already received a stem cell transplant from the same donor.

This helps boost the attack on leukemia cells. DLI is used to kill the remaining CML cells that have not gone away completely or have come back following the transplant.

Immunotherapy uses substances that stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way. It may be a treatment option for CML, but it is not typically used as the first treatment.

The type of treatment used for CML is cytokine immunotherapy. It is known as nonspecific immune stimulation and aids in immune cell communication. For CML, alpha interferon is the most commonly used type that boosts the ability of certain immune cells to attack cancer cells.

Chemotherapy uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It may be given alone or with other treatments, such as surgery or radiation therapy. It is an option for treatment and is used especially for CML that does not respond to targeted therapy and then progresses to an advanced phase (accelerated or blast phase). It may also be used to treat CML that has not improved after treatment with TKIs.

Corticosteroids are drugs used to treat some blood cancers and can be used alone or in combination with other drug therapies. Corticosteroids also help reduce inflammation and may offer other benefits.

Surgery may be used to remove an enlarged spleen (splenectomy).

Clinical trials may be an option to consider. Ask your doctor or research trials on your own to see if any may be available for you. Examples include trials for new treatments for relapsed or resistant CML, ways to prevent a recurrence or methods to reduce the side effects of treatment.

Monitoring and Treatment Milestones

Throughout treatment and after, you will be monitored closely so that your doctor can ensure your response is as effective as possible. This may include having multiple blood tests, imaging studies and, possibly, bone marrow biopsies. Your doctor will watch to see how the cancer responds to treatment, including if it develops a new mutation, returns or becomes resistant to the current therapy.

Before treatment begins, your doctor may perform a special polymerase chain reaction (PCR) test called a quantitative reverse transcriptase polymerase chain reaction (qPCR). It uses a blood sample to measure the number of cells carrying the BCR-ABL1 gene. The results will be compared to a baseline known as the International Scale (IS). This test will be repeated frequently after you begin treatment (approximately every three months for two years and every three to six months thereafter) to monitor your treatment’s effectiveness at controlling the leukemia.

When CML reaches the accelerated phase or blast phase, it is known as advanced phase CML. When this occurs, additional testing may be required to determine if the blast cells are myeloid or lymphoid, if new chromosomal abnormalities besides the Philadelphia chromosome have developed and if a stem cell transplant is an option.

If your CML progresses to an advanced phase, your doctor will also test for new mutations in the BCR-ABL1 gene, which may lead to resistance to some targeted therapies. As a result, your doctor may adjust your disease management plan.

Doctors measure treatment response with milestones. They compare your test results to expected milestones to determine if your treatment is working effectively. If not, your treatment may be adjusted or new options may be considered. Therefore, keeping follow-up appointments and communicating new symptoms to your doctor between appointments is crucial for catching changes early so that your treatment can be modified as necessary.

Response milestones include hematologic (blood), cytogenetic and molecular responses (see Table 3). The two most important milestones are early molecular response, which indicates how well the treatment will work in the long term, and complete cytogenetic response, which occurs when the Philadelphia chromosome cannot be found through testing.

Response Indications
Hematologic
Complete hematologic (blood) response Normal levels of white blood cells and platelets
No immature cells (myelocytes or blasts)
Spleen is normal size
No CML symptoms
Partial hematologic response Blood counts are not normal
Some blasts remain in the blood
Spleen may be enlarged
Symptoms and blood counts have improved since initial treatment started
Cytogenetic
Complete cytogenetic response No cells with Philadelphia (Ph) chromosome
Major cytogenetic response Philadelphia chromosome positive (Ph+) cells found in 0% to 35% of cells
Partial ytogenetic response (Ph+) cells found in 1% to 35% of cells
Minor cytogenetic response (Ph+) cells found in 36% to 65% of cells
Molecular
Complete molecular response No cells with BCR-ABL1 fusion found
Major molecular response Level of BCR-ABL1 gene is very small (more than 1,000 times fewer than when diagnosed)
Early molecular response Level of BCR-ABL1 gene is 10% or less at 3 and 6 months

Traveling For Treatment

You are encouraged to consider a doctor with expertise in CML, and if a stem cell transplant is part of your plan, a center with extensive experience in stem cell transplantation. This may require you to travel. Some treatment centers and organizations offer assistance with travel and temporary lodging during treatment. Talk with your health care team at the transplant center and advocacy organizations to learn about the resources available to assist.

Who’s on the Healthcare Team

Your multidisciplinary team may include many of the following specialists, as well as other health care professionals.

Hematologist: A doctor who has special training in diagnosing and treating blood disorders

Medical oncologist: Trained to treat cancer using medicines

Nurse navigator: Guides a patient and their caregiver through the healthcare system. Your nurse navigator will be your go-to resource who knows your case – and you – the best.

Pathologist: Has special training in identifying diseases by studying cells and tissues under a microscope

Radiation oncologist: Uses radiation therapy to treat cancer

Social worker: The patient’s personal advocate who acts on their behalf by collaborating with health care professionals and non-medical personnel to help overcome various financial, logistical and other common barriers to care.

Donor Stem Cells Can Save Lives

At any given moment, thousands of people need lifesaving blood stem cell transplants but have no available donor. Organizations such as Be The Match (operated by the National Marrow Donor Program) have created registries of millions of potential donors. Minority donors are especially needed.

Learn more at www.bethematch.org

Relapsed and Resistant CML

The goal of treating CML is to reach remission, which occurs when cancer cells can no longer be found after multiple tests. Even with complete remission, small numbers of cancer cells may still be in the body. A partial remission occurs when some but not all signs and symptoms have decreased or disappeared.

CML may return (relapse) after treatment. If that happens, your doctor will begin a new cycle of testing to determine any changes in your blood counts and physical symptoms. A new treatment plan may be developed for relapsed CML. You may also want to consider finding a clinical trial.

Sometimes CML stops responding to treatment, which is called resistance. It is possible for CML to become resistant to targeted therapies. A treatment plan for resistant CML may use a combination of therapies, which may include switching targeted therapies. Another option may be a clinical trial.

Drug Therapies for CML
asciminib (Scemblix)
bosutinib (Bosulif)
busulfan (Busulfex, Myleran)
cyclophosphamide
cytarabine
dasatinib (Sprycel)
hydroxyurea (Hydrea)
imatinib mesylate (Gleevec)
nilotinib (Tasigna)
omacetaxine mepesuccinate (Synribo)
ponatinib (Iclusig)
As of 10/29/21