Leukemia--Acute Myeloid (Myelogenous)

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Treating Leukemia - Acute Myeloid (AML) TOPICS

Stem cell transplant for acute myeloid leukemia

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 the bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other problems due to low blood cell counts.

A stem cell transplant (SCT) allows doctors to use higher doses of chemotherapy (sometimes combined with radiation therapy). After that treatment is finished, the patient receives an infusion 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). Sometimes stem cells harvested from a baby’s umbilical cord are used.

Types of transplants

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

Allogeneic stem cell transplant

This is the most common form of SCT used to treat acute leukemia. 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 ideal donor is a close relative, such as a brother or sister, if they are a match. If no close relatives match, a matched unrelated donor (MUD) may be an option in some cases, but use of stem cells from a MUD is linked to more complications. 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.

Using donor cells for SCT for acute myeloid leukemia (AML) is preferred because leukemia is a disease of the blood and bone marrow, so giving the patient his or her own cells back may mean giving leukemia cells. Donor cells are also helpful because of the “graft versus leukemia” effect. When the donor immune cells are infused into the body, they may recognize any remaining leukemia cells as being foreign to them and will attack them. This effect doesn’t happen with autologous stem cell transplants

An allogeneic transplant is often the preferred type of transplant for AML when it is available, but its use is limited by the need for a matched donor. It is also limited by its side effects, which are too severe for most older people.

Non-myeloablative transplant (mini-transplant): Many older people 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 an experimental procedure for AML, and studies are under way to determine how useful it may be.

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 put back (reinfused) into the patient’s blood after treatment.

Autologous transplants are sometimes used for people with AML who are in remission after initial treatment and who don’t have a matched donor for an allogeneic transplant. Some doctors feel that it is better than standard “consolidation” chemotherapy (see section called “Typical treatment of acute myeloid leukemia”) for these people, but not all doctors agree with this.

Autologous transplants are generally easier to tolerate than allogeneic transplants, but the high-dose chemotherapy can still cause major side effects. The patient is getting his or her own cells back, so the risk of some complications is smaller. This type of transplant can be done in any otherwise healthy person, although very old patients might not be suitable.

One problem with autologous transplants is that it is hard to separate normal stem cells from leukemia cells in the bone marrow or blood samples. Even after purging (treating the stem cells in the lab to try to kill or remove any remaining leukemia cells), there is the risk of returning some leukemia cells with the stem cell transplant.

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 an allogeneic SCT, the person getting the transplant is given drugs to keep the new immune system in check. For the next few weeks the patient will get 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 need to stay in the hospital until their neutrophil count (often called the ANC) rises to a safer level (at least 500, but sometimes 1,500 is the target). Other factors also affect the discharge date, like the type of transplant, the presence of an infection or other complications, and the ability of the patient to be followed-up in the outpatient clinic. After discharge from the hospital, the patient is seen in the outpatient clinic for several weeks, often daily. Because platelet counts take longer to return to a safe level, patients may get platelet transfusions as an outpatient.

Practical points

Bone marrow or peripheral blood SCT is a complex treatment. If the doctors think a patient might 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 lengthy hospital stay. Because some types of SCT may be viewed as “experimental” by insurance companies, 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 chemotherapy (see the section “Chemotherapy for acute myeloid leukemia” for details), although they may be more severe. These side effects are due to damage to the bone marrow and other quickly dividing tissues of the body. They can include low blood cell counts (with fatigue and an 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 for 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.
  • 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.

Graft-versus-host disease is the most serious complication of allogeneic (donor) stem cell transplants. The most common symptoms are severe skin rashes and severe diarrhea. The liver and lungs may also be damaged. The patient may also become tired easily and have muscle aches. Sometimes the graft-versus-host disease becomes chronic and disabling and, if it is severe enough, can be life-threatening. Drugs that affect the immune system may be given to try to control it.

On the positive side, graft-versus-host disease also leads to “graft-versus-leukemia” activity. Any leukemia cells remaining after chemotherapy and radiation therapy may be killed by the immune reaction of the donor cells.

For more information on stem cell transplants, see our document called Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants).


Last Medical Review: 07/24/2013
Last Revised: 02/07/2014