Bone Marrow or Peripheral Blood Stem Cell Transplantation

/Home/Leukemia Cures and Treatment/Leukemia and Transplant/Leukemia and Stem Cell Transplants

Bone Marrow or Peripheral Blood Stem Cell Transplantation
American Cancer Society, Inc.

Last Revised: 08/03/2007

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 the severe damage to bone marrow cells would cause lethal shortages of blood cells and damage to vital organs.

If the patient is going to have a stem cell transplant (SCT), doctors can 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 Bone marrow transplants were more common in the past, but they have has largely been replaced by PBSCT.

Types of Transplants

There are 2 main types of stem cell transplants: they differ in the source of the blood-forming stem cells.

In an allogeneic stem cell 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 present 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 or a matched unrelated donor (MUD). The stem cells from an unrelated donor come from volunteers whose tissue type has been stored in a central registry and matched with the patient’s tissue type. 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.

There is an important reason to use allogeneic stem cells (from someone else) for transplantation. These cells seem to help fight any remaining leukemia cells through an immune reaction. This is called a "graft-versus-leukemia" reaction. Studies of this approach are still going on.

Although an allogeneic transplant is the preferred type of transplant for ALL when it is available, its use is limited because of the need for a matched donor. Its use is also limited by its side effects, which are too severe for most people over 55 to 60 years old.

In an autologous stem cell transplant, a patient's own stem cells are removed from his or her bone marrow or peripheral blood. They are stored while the person gets treatment (high-dose chemotherapy and/or radiation) and then are reinfused into the patient's blood.

Autologous transplants are sometimes used for people with ALL who are in remission. Some doctors feel that it is better than standard "consolidation" chemotherapy (see below), 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 (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 chemotherapy and radiation treatments are meant to destroy any remaining cancer cells. They also kill the normal cells of the bone marrow and the immune system. This prevents the stem cell transplant (graft) from being rejected. 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 such as prednisone and methotrexate or cyclosporine to prevent acute graft-versus-host-disease (GVHD). In this condition, the immune cells in the donor’s marrow or cord blood (the graft) attack the patient’s body (the host). 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 receive platelet transfusions as an outpatient.

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 lengthy 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 and to have an idea of what you might have to pay.

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 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 infections.. 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 fatal. 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 (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. It occurs because the immune system of the patient is taken over by that of the donor. The donor immune system then begins reacting against the patient's other tissues and organs.

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 GVHD becomes chronic and disabling and, if it is severe enough, can be fatal. 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 the chemotherapy and radiation therapy may be killed by the immune reaction of the donor cells.

Non-myeloablative Transplant (Mini-transplant)

Most patients over the age of 55 will not be able to tolerate a standard allogeneic transplant that uses high doses of chemotherapy. Some, however, 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 small doses of certain chemotherapy drugs and low doses of total body radiation, an allogeneic transplant can still 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.

This procedure is still considered experimental, but is being studied to determine how useful it may be against ALL.

Copyright 2009 © American Cancer Society, Inc.