Stem cell transplants are sometimes used to treat lymphoma patients who are in remission or who have a relapse during or after treatment. Although only a small number of patients with lymphoma are treated with this therapy, this number is growing.

Stem cell transplants allow doctors to use higher doses of chemotherapy than would normally be tolerated. High-dose chemotherapy destroys the bone marrow, which prevents new blood cells from being formed. This could lead to life-threatening infections, bleeding, and other problems due to low blood cell counts.

Doctors try to get around this problem by giving an infusion of blood-forming stem cells after treatment. Stem cells are very primitive cells that can create new blood cells.

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). Peripheral blood stem cells are obtained from a procedure similar to a blood donation, while bone marrow donation is usually done in an operating room under general anesthesia (while the donor is asleep). Bone marrow transplants were more common in the past, but they have largely been replaced by PBSCTs.

Types of transplants

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

Allogeneic stem cell transplant: In this type of transplant, the stem cells come from someone else. The donor's tissue type (also known as the HLA type) should be almost identical to the patient's tissue type 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 can come from 1 of 3 sources:

• bone marrow: The stem cells are collected from the donor during several bone marrow aspirations.

• peripheral (circulating) blood: The stems cells are taken from the blood during apheresis. This procedure is similar to donating blood, but instead of going into a collecting bag, the blood goes into a special machine that filters out the stem cells and returns the other parts of the blood to the person's body. This is now more common than collecting cells from the bone marrow.

• umbilical cord blood: These stem cells are collected from the umbilical cord attached to the placenta after a baby is born and the umbilical cord is cut. (This blood is rich in stem cells.) The blood is then frozen and stored until it is needed by someone with the same tissue type. Cord blood is becoming a more common source of stem cells, although there are a limited number of specimens available.

Allogeneic transplants have limited usefulness in treating lymphoma because it is often hard to find a matched donor. Another drawback is that side effects of this treatment are often too severe for most people over 55 years old. About 1 out of 4 transplants for lymphoma is of this kind.

Autologous stem cell transplant: In this type of transplant, a patient's own stem cells are removed from his or her bone marrow or peripheral blood. They are collected on several occasions in the weeks before treatment. The cells are frozen and stored while the person gets treatment (high-dose chemotherapy and/or radiation) and are then are reinfused into the patient's blood.

Some types of lymphoma tend to spread to the bone marrow or blood, so an autologous transplant may not be possible because it may be hard to get a stem cell sample that is free of lymphoma cells. Even after purging (treating the stem cells in the lab to kill or remove lymphoma cells), it's possible to return some lymphoma cells with the stem cell transplant.

The transplant procedure

The patient getting the stem cell transplant may be admitted to the bone marrow transplant (BMT) 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 chemotherapy begins. He or she will usually stay in the hospital until after the chemotherapy 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.

Treatment starts with high-dose chemotherapy and may include high-dose whole body radiation. 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 by the body. Once treatment is complete, the stem cells (autologous or allogeneic) are given through a vein, just like a blood transfusion. The stem cells migrate to the bone marrow.

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 several weeks the patient is given as much supportive therapy as needed. This may include antibiotics, red blood cell or platelet transfusions, other medicines, and help with nutrition.

Usually around 2 to 3 weeks after the stem cells have been infused, they begin making new white blood cells. This is followed by the new platelet production and, several weeks later, by new red blood cell production. Because of the high risk of serious infections right after treatment, patients remain in protective isolation (where exposure to germs is kept to a minimum) until a measure of their white blood cells -- the absolute neutrophil count (ANC) -- rises above 500. They can usually leave the hospital when their ANC nears 1,000.

Patients then typically make regular visits to the outpatient transplant clinic for about 6 months, after which time their care is continued by their regular doctors. At this point, they may only come back to the clinic for regular exams or if they have symptoms that should be checked by their 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 stem cell transplant programs may not have experience in certain types of transplants, especially transplants from unrelated donors.

SCT is very expensive (often costing 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. Find out what your insurer will cover before deciding on a transplant so you will have an idea of what you might have to pay.

Possible side effects

Side effects from a stem cell transplant 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 growing tissues of the body. They can include low blood cell counts (with fatigue and increased risks 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 occurs only in allogeneic transplants (see below)
• infertility and premature menopausal symptoms in female patients (caused by damage to the ovaries)
• infertility in male patients
• damage to the thyroid gland that can cause problems with metabolism
• cataracts (damage to the lens of the eye that can affect vision)
• damage to the lungs, causing shortness of breath
• bone damage called aseptic necrosis (if damage is severe, the patient may need to have part of the affected bone and the joint replaced)
• possible development of leukemia several years later

Graft-versus-host disease (GVHD): This is one of the most serious complications 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 may recognize the patient's own body tissues as foreign and may react against them. Symptoms can include severe skin rashes, itching, mouth sores (which can affect eating), nausea, and severe diarrhea. Liver damage may cause yellowing of the skin and eyes (jaundice). The lungs may also be damaged. The patient may also become easily fatigued and develop muscle aches.

GVHD is often described as either acute or chronic, based on how soon after the transplant it begins. Sometimes GVHD can become disabling, and if it is severe enough, it can be life-threatening. Usually, immune suppressing drugs can be used to help control GVHD.

On the positive side, the graft-versus-host disease also leads to "graft-versus-lymphoma" activity. Any lymphoma cells remaining after the chemotherapy and radiation therapy are often killed by immune reactions of the donor cells since the lymphoma cells are seen as foreign by the donor's immune system as well. Mild graft-versus-host disease can be a good thing.

Non-myeloablative transplant (mini-transplant)

Most patients over the age of 55 can't 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. They then receive the allogeneic (donor) stem cells. These cells enter the body and establish a new immune system, which sees the lymphoma cells as foreign and attacks them (a "graft-versus-lymphoma" 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, which may damage the patient's body tissue.

For more information on these procedures, see our document, Bone Marrow and Peripheral Blood Stem Cell Transplants.

Last Medical Review: 07/17/2009
Last Revised: 07/17/2009