Stem Cell Transplant for Chronic Myeloid Leukemia: What Do You Need to Know?

Chronic myeloid leukemia is a type of blood cancer that affects the production of granulocytes (a kind of white blood cell) from the bone marrow (the spongy, red tissue that fills large bones).

When someone has CML, a genetic change takes place in immature versions of myeloid cells, which create red blood cells, platelets, and most types of white blood cells. This change forms an abnormal gene called BCR-ABL1, which turns into a CML cell. These cells then build up in the bone marrow and spill over into the blood. They can eventually spread to other parts of the body.

Thus, chronic myeloid leukemia (CML) is an acquired disease from a gene mutation and is neither inherited (passed down from generation to generation) nor contagious. Although the reason behind this mutation remains unknown, some scientific data support that the following risk factors may increase your chances of getting chronic myeloid leukemia (CML), these include the following:

• Age the older you are, the higher your chances
• Gender Men are more susceptible to CML
• Exposure to radiation

Phases of Chronic Myeloid Leukemia

There are three phases of CML: chronic, accelerated, and blast. Classifying someone into these phases depends on the number of blast cells in the blood or bone marrow. About 90% are diagnosed with CML at the chronic phase when there are no significantly noticeable symptoms through routine checkups and abnormal blood work.

• Chronic phase: Approximately 85% of people are in the chronic phase of CML when they are initially diagnosed. In chronic phase CML, there are less than 5 percent immature leukemic blast cells (the abnormal white blood cells) in the bone marrow. Chronic phase CML is well controlled with oral medications in nearly all cases. Left untreated, patients will eventually progress to the accelerated or blast phase. However, this can take years to happen.
• Accelerated phase: During the accelerated phase, the white blood cells become increasingly unable to mature normally, and there are between 10% – 20% leukemic blast cells in the blood or bone marrow. In this phase, symptoms like night sweats, fatigue, weight loss, and frequent infections start to manifest more clearly as the number of blast cells starts to increase. Accelerated phase CML is more difficult to control with medications, probably because of new mutations that develop in the CML cells. This stage can take from three to nine months. Similarly, if left untreated patients will progress to the blast phase.
• Blast phase: In blast phase of CML (also called “blast crisis”), there are more than 20% blast cells in the blood or bone marrow. This is the last phase of chronic myeloid leukemia and leukemia has become more aggressive with noticeable symptoms. This phase is also called the 'blast crisis'. CML can progress to blast phase from the chronic or accelerated phase, or in some cases a person is already in the blast phase at the time of diagnosis. Blast phase CML is difficult to control with medications. Unfortunately, at the blast phase if patients aren't treated it's most probably fatal.

Most Common Treatments

The main treatment for CML are targeted cancer drugs (such as tyrosine kinase inhibitors). Other possible treatments include chemotherapy and a stem cell transplant.

• Targeted Treatment: For most people, CML is treated with an oral medication, called a tyrosine kinase inhibitor (TKI). This medication blocks the effects of BCR::ABL1 (the abnormal protein found in people with CML).
• Chemotherapy: Drugs that carry toxic substances that inhibit the cancer cells. These are mostly used when TKIs aren't effective, or they cause intolerable side effects. (ex. hydroxycarbamide).
• Stem cell transplantation: Also called bone marrow transplantation is usually used after the disease stops responding or relapses during treatment with a TKI.

Stem cell transplantation

Stem cell transplantation may be recommended if CML stops responding or relapses during treatment with a TKI, and for some patients with accelerated phase or blast phase CML.

Stem cell transplantation replaces diseased bone marrow cells with healthy bone marrow. For chronic myeloid leukemia, this requires healthy stem cells donated by another person (allogeneic transplant). The transplanted stem cells generate a new immune system for the person with CML, which recognizes the leukemia cells as foreign and attempts to destroy them. This beneficial reaction against the CML cells is called the graft-versus-tumor effect.

In CML, the chances of successfully controlling CML with stem cell transplantation are related to your age and the phase of disease at the time of the transplant. Younger patients generally tolerate transplantation better than older patients. Transplantation is also more likely to be successful when CML has been restored to chronic phase. Most people will be treated with a TKI before transplantation with the hope of restoring accelerated or blast phase CML to chronic phase.

Stem cell transplant or a bone marrow transplant?

A stem cell transplant uses stem cells from the bloodstream, also called a peripheral blood stem cell transplant. Whereas, a bone marrow transplant uses stem cells directly from the bone marrow.

Nowadays, stem cell transplants are the most common type of transplant. And doctors don’t often use bone marrow transplants any more.  This is because it's easier to collect stem cells from the bloodstream than bone marrow, your treatment team can usually collect more cells from the bloodstream and blood counts tend to recover quicker following a stem cell transplant. Many patients assume the transplant is a surgery, however it is not.  In fact it also does not require an injection into the bones – instead it is an intravenous (IV) infusion of stem cells.

Transplant Donor

For chronic myeloid leukemia, it is required that healthy stem cells are donated by another person (allogeneic transplant). A person can get stem cells from:

• A sibling
• An unrelated person with similar stem cells
• Umbilical cord blood

In some situations, you might have stem cells from a half match for example, from one of your parents. This is called a haploidentical match.

Graft-versus-host disease

Donor immune cells can also attack other organs in the body, including the skin, liver, and gastrointestinal tract. This is known as “graft-versus-host disease” (GVHD) and can be a severe and sometimes fatal complication. It is worth mentioning that GVHD can be mild to severe – not always severe.

Before a transplant, tissue and cells from possible donors are checked to see how closely they match the recipient. GVHD is less likely to occur, or symptoms will be milder, when the match is close. The chance of GVHD is:

• Around 35% to 45% when the donor and recipient are related
• Around 60% to 80% when the donor and recipient are not related

After a transplant, the recipient usually takes medicines, such as prednisone (a steroid), which suppresses the immune system. This helps reduce the chances (or severity) of GVHD. You’ll continue taking the medicines until your health care provider thinks the risk for GVHD is low.

Other Side Effects

Side effects can happen with any type of treatment, but everyone's experience is different. Some people may have many side effects. Others have fewer.

Side effects can happen any time during, immediately after, or days to months after a stem cell transplant. Short-term (acute) side effects generally develop during the first 100 days after a stem cell transplant. Long-term (chronic) side effects generally develop 100 or more days after the transplant. Most side effects go away on their own or can be treated, but some side effects can last a long time or become permanent.

Side effects of a stem cell transplant will depend mainly on:

• The type and dose of chemotherapy drugs used as conditioning therapy before the transplant
• The dose of radiation therapy if it was given before the transplant
• The type of transplant done
• How good a match the donor stem cells are
• Your age and overall health

A stem cell transplant is very complex. It can take 6 to 12 months or longer for your blood counts to be back to normal and your immune system to work well. Side effects of a stem cell transplant can be very serious or even life-threatening. The healthcare team will watch you closely during this time. They will take measures to prevent side effects and will quickly deal with any side effects that develop.

Side effects may include:

• Weakened immune system: increased risk of getting an infection
• Fatigue: tiredness and lacking energy
• Increased risk of bleeding and anemia
• Sore mouth and throat
• Loss of appetite
• Weight loss
• Diarrhea
• Nausea and vomiting.

Questions to Ask Your Doctor

• Am I eligible to receive a bone marrow transplant?
• Who can be my donor?
• Am I more, or less, likely to respond to this treatment?
• How will I feel during treatment? What are the most common side effects of it?
• Should I get a second option regarding my treatment?

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