Leukemia--Acute Lymphocytic

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Treating Leukemia - Acute Lymphocytic (ALL) in Adults TOPICS

High-dose chemotherapy and stem cell transplant for acute lymphocytic leukemia

Standard doses of chemotherapy aren’t always able to cure acute lymphocytic leukemia (ALL). Even though higher doses of chemo 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 and, sometimes, radiation therapy. After these treatments are 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 Bone marrow transplants were more common in the past, but they have largely been replaced by PBSCT.

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. The donor’s tissue type (also known as the HLA type) needs to match the patient’s tissue type as closely as possible to help prevent the risk of major problems with the transplant. Usually this donor is a brother or sister if they have the same tissue type as the patient. If there are no siblings with a good match, the cells may come from an HLA-matched, unrelated donor – a stranger who has volunteered to donate their cells.

The stem cells for an allogeneic SCT are usually collected from a donor’s bone marrow or peripheral (circulating) blood on several occasions. In some cases, the source of the stem cells may be blood collected from an umbilical cord attached to the placenta after a baby is born (which is rich in stem cells). Regardless of the source, the stem cells are then frozen and stored until they are needed for the transplant.

An allogeneic stem cell transplant may be more effective than an autologous transplant 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 the preferred type of transplant for ALL when it is available, but its use is limited because of the need for a matched donor. Its use is also limited by its side effects, which are often too severe for most people over 55 to 60 years old or for those who have other health problems.

Non-myeloablative transplant: Some people over the age of 55 might not be able to tolerate a standard allogeneic transplant that uses high doses of chemotherapy. However, they 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. Then they 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 smaller doses of certain chemotherapy drugs and lower doses of total body radiation, an allogeneic transplant can still sometimes work with much less toxicity. In fact, some patients can receive a non-myeloablative transplant as an outpatient. The major complication is graft-versus-host disease (discussed in detail later in this section).

This is not a standard treatment for ALL, and is being studied 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. A process called purging may be done in the lab to try to remove leukemia cells in the samples. The stem cells are then frozen and stored while the person gets treatment (high-dose chemotherapy and/or radiation). The patient then receives the stem cells after treatment.

Autologous transplants are sometimes used for people with ALL who are in remission after initial treatment. Some doctors feel that it is better than standard consolidation chemotherapy (see “Typical treatment of acute lymphocytic leukemia”), but not all doctors agree with this.

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, there is the risk of returning some leukemia cells with the stem cell transplant.

The transplant procedure

The patient getting the stem cell transplant may be admitted to the stem cell transplant unit of the hospital or receive treatment as an outpatient depending on a number of factors.

If treated as an inpatient, the patient is usually admitted to the hospital on the day before the high-dose chemo begins. He or she will usually stay in the hospital until after the chemo and the stem cells have been given, and until the stem cells have started making new blood cells again (see below).

If this is done as an outpatient procedure, patients and their families must be able to spot complications requiring their doctor’s attention. Unless they live close to the transplant center, they will be asked to stay in a nearby hotel.

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 may be given drugs to keep the new immune system from attacking the body (known as graft-versus-host disease). For the next few weeks the patient will probably have very low blood cell counts, so they will be given supportive therapies, as needed. This 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 later followed by new platelet production and new red blood cell production.

Because of the high risk of serious infections right after treatment, patients usually stay in the hospital in protective isolation (guarding against exposure to germs) until a measure of their white blood cell count – the absolute neutrophil count (ANC) – rises above 500. They may be able to leave the hospital when their ANC is near 1,000.

The patient is then seen in an outpatient transplant clinic almost every day for several weeks. Because platelet counts take longer to return to a safe level, patients may get platelet transfusions as an outpatient. Patients may make regular visits to the outpatient clinic for about 6 months, after which time their care may be continued by their regular doctors.

Practical points

Bone marrow or peripheral blood SCT is a complex treatment that can cause life-threatening side effects. 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 or mismatched donors.

SCT is very expensive (often costing well over $100,000) and often means a lengthy hospital stay. Because some insurance companies may view it as an experimental treatment, they may not pay for the procedure. Even if the transplant is covered by your insurance, your co-pays or other costs could easily amount to tens of thousands of dollars. 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.

Early or short-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 section about chemotherapy), and can be severe. They are due to damage to the bone marrow and other quickly dividing tissues of the body and can include:

  • Low blood cell counts (with fatigue and an increased risk of infection and bleeding)
  • Nausea and vomiting
  • Loss of appetite
  • Mouth sores
  • Diarrhea
  • Hair loss

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

A rare but serious side effect of stem cell transplant is called veno-occlusive disease of the liver (VOD), also known as sinusoidal obstruction syndrome. In this disease, the high doses of chemo given for the transplant damage the liver. Symptoms include weight gain (from fluid retention), liver enlargement, and jaundice (yellowing of the skin and eyes). When severe, it can lead to liver failure, kidney failure, and even death.

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

  • Graft-versus-host disease (GVHD), which can occur only in allogeneic (donor) transplants.
  • 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 ( 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.
  • Development of another leukemia (or other type of cancer) several years later

Graft-versus-host disease is one of the most serious complications of allogeneic (donor) stem cell transplants. This happens when the donor immune system cells attack the patient’s normal cells and tissues.

The areas most often affected include the skin, liver, and digestive tract, but other areas may be affected as well. GVHD is often described as either acute or chronic, based on how soon after the transplant it begins. In severe cases, GVHD can be life-threatening. Drugs that weaken the immune system are given as a part of the transplant to try to prevent GVHD, although they may have their own side effects.

The most common symptoms of GVHD are severe skin rashes and severe diarrhea. If the liver is affected, the damage can lead to jaundice (yellowing of the skin and eyes) or even liver failure. GVHD can also cause lung damage, leading to problems breathing. The patient may feel weak, become tired easily, and have muscle aches.

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

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


Last Medical Review: 07/10/2013
Last Revised: 02/07/2014