The usual doses of chemotherapy drugs can cause serious side effects to quickly dividing tissues such as the bone marrow. Even though higher doses of these drugs might be more effective, they are not given because they could severely damage to bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other problems because of low blood cell counts.

A stem cell transplant (SCT) allows doctors to use higher doses of chemotherapy and, sometimes, radiation therapy. After treatment is finished, the patient receives a transplant of blood-forming stem cells to restore the bone marrow.

Blood-forming stem cells used for a transplant are obtained either from the blood (for a peripheral blood stem cell transplant, or PBSCT) or from the bone marrow (for a bone marrow transplant, or BMT). Bone marrow transplant was more common in the past, but it has largely been replaced by PBSCT.

It's not yet clear how helpful stem cell transplants are in patients with CLL. When these treatments are used, it is most often in clinical trials looking to test their effectiveness.

Types of transplants

There are 2 main types of stem cell transplants: allogeneic and autologous. They differ in the source of the blood-forming stem cells.

Allogeneic stem cell transplant: In an allogeneic transplant, the stem cells come from someone else - usually a donor whose tissue type is almost identical to the patient's. Tissue type is based on certain substances on the surface of cells in the body. These substances can cause the immune system to react against the cells. Therefore, the closer a tissue match is between the donor and the recipient, the better the chance the transplanted cells will take and begin making new blood cells.

The donor may be a brother or sister if they are a good match. Less often, a matched unrelated donor may be found. The stem cells from an unrelated donor come from volunteers whose tissue type has been stored in a central registry and matched with that of the patient. Sometimes umbilical cord stem cells are used. These stem cells come from blood drained from the umbilical cord and placenta after a baby is born and the umbilical cord is cut.

Allogeneic transplants are being studied in patients with CLL, although it's not yet clear how effective they are. Because this type of transplant can cause severe or even life-threatening complications and side effects, it may not be a good option in people who are older or have other health problems.

Autologous stem cell transplant: In an autologous transplant, a patient's own stem cells are removed from his or her bone marrow or peripheral blood. They are frozen and stored while the person gets treatment (high-dose chemotherapy and/or radiation). A process called purging may be used to try to remove any leukemia cells in the samples. The stem cells are then reinfused into the patient's blood after treatment.

Autologous transplants are generally easier for patients to tolerate than allogeneic transplants. The patient is getting his or her own cells back, so the risk of complications is smaller. This type of transplant can be done in any otherwise healthy person, although it might not be suitable for elderly patients.

Autologous stem cell transplants are being studied for use in CLL, but so far it isn't clear if they improve survival compared with standard treatment.

The transplant procedure

Blood-forming stem cells from the bone marrow or peripheral blood are collected, frozen, and stored. The patient receives high-dose chemotherapy and sometimes also radiation treatment to the entire body. (Radiation shields are used to protect the lungs, heart, and kidneys from damage during radiation therapy.)

The treatments are meant to destroy any cancer cells in the body. They also kill the normal cells of the bone marrow and the immune system. After these treatments, the frozen stem cells are thawed and given as a blood transfusion. The stem cells settle into the patient's bone marrow over the next several days and start to grow and make new blood cells.

In allogeneic SCTs, the person getting the transplant may be given drugs to keep the new immune system in check. For the next few weeks the patient gets regular blood tests and supportive therapies as needed, which might include antibiotics, red blood cell or platelet transfusions, other medicines, and help with nutrition.

Usually within a couple of weeks after the stem cells have been infused, they begin making new white blood cells. This is followed by new platelet production and, several weeks later, new red blood cell production.

Patients usually stay in the hospital in protective isolation (guarding against exposure to germs) until their white blood cell count rises above 500. They may be able to leave the hospital when their white blood cell count is near 1,000. Because platelet counts take longer to return to a safe level, patients may get platelet transfusions as outpatients.

Patients typically make regular visits to the outpatient clinic for about 6 months, after which their care is continued by their cancer doctor.

Practical points

Bone marrow or peripheral blood SCT is a complex treatment. If the doctors think a patient may benefit from a transplant, it should be done at a hospital where the staff has experience with the procedure and with managing the recovery phase. Some bone marrow transplant programs may not have experience in certain types of transplants, especially transplants from unrelated donors.

SCT is very expensive (more than $100,000) and often requires a long hospital stay. Because some insurance companies may view it as an experimental treatment, they may not pay for the procedure. It is important to find out what your insurer will cover before deciding on a transplant to get an idea of what you might have to pay.

Possible side effects

Side effects from SCT are generally divided into early and long-term effects.

The early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy (see the "Chemotherapy" section of this document), and are caused by damage to the bone marrow and other quickly dividing tissues of the body. They can include low blood cell counts (with fatigue and increased risk of infection and bleeding), nausea, vomiting, loss of appetite, mouth sores, and hair loss.

One of the most common and serious short-term effects is the increased risk of infection from bacteria, viruses, or fungi. Antibiotics are often given to try to prevent this from happening. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.

Some complications and side effects can persist for a long time or may not occur until months or years after the transplant. These include:

• Graft-versus-host disease (GVHD), which can occur in allogeneic (donor) transplants. This happens when the donor immune system cells attack tissues of the patient's skin, liver, and digestive tract. Symptoms can include weakness, fatigue, dry mouth, rashes, nausea, diarrhea, yellowing of the skin and eyes (jaundice), and muscle aches. In severe cases, GVHD can be life-threatening. GVHD is often described as either acute or chronic, based on how soon after the transplant it begins. Drugs that weaken the immune system are often given to try to keep GVHD under control.

• Radiation damage to the lungs, causing shortness of breath

• Damage to the ovaries in women, causing infertility and loss of menstrual periods

• Damage to the thyroid gland that causes problems with metabolism

• Cataracts (damage to the lens of the eye that can affect vision)

• Bone damage called aseptic necrosis (where the bone dies because of poor blood supply). If damage is severe, the patient will need to have part of the bone and the joint replaced.

Non-myeloablative transplant (mini-transplant)

Many people over the age of 55 can't tolerate a standard allogeneic transplant that uses high doses of chemotherapy. Some may be able to have a non-myeloablative transplant (also known as a mini-transplant or reduced-intensity transplant), where they receive lower doses of chemotherapy and radiation that do not completely destroy the cells in their bone marrow. They then receive the allogeneic (donor) stem cells. These cells enter the body and establish a new immune system, which sees the leukemia cells as foreign and attacks them (a graft-versus-leukemia effect).

Doctors have learned that if they use small doses of certain chemotherapy drugs and low doses of total body radiation, an allogeneic transplant can still sometimes work with much less toxicity. In fact, a patient can receive a non-myeloablative transplant as an outpatient. The major complication is graft-versus-host disease.

Many doctors still consider this procedure to be experimental, and studies are under way to determine how useful it may be against CLL.

For more information on stem cell transplants, see the American Cancer Society document, Bone Marrow & Peripheral Blood Stem Cell Transplants.

Last Medical Review: 07/27/2009
Last Revised: 07/27/2009