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 in treating the lymphoma, they are not given because the severe damage to bone marrow cells would cause lethal shortages of blood cells, and other vital organs would likely be damaged as well.

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). 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 Bone marrow transplants were more common in the past, but they have largely been replaced by PBSCTs.

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 -- 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 that of the patient. Sometimes umbilical cord stem cells are used. These cord blood 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 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 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 stored while the person gets treatment (high-dose chemotherapy and/or radiation) and then are reinfused into the patient's blood.

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

With either type of transplant, the blood-forming stem cells are carefully frozen and stored before treatment. The patient then receives high-dose chemotherapy and sometimes whole body radiation treatment as well. (Radiation shields are used to protect the lungs, heart, and kidneys from damage during radiation therapy.)

This destroys remaining cancer cells, but it also kills all or most normal cells in the bone marrow. After therapy, the frozen stem cells are thawed and returned to the body like 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.

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 (BMT unit) until after the high-dose 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.

After the proper education, the patient starts high-dose chemotherapy and may be given 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. Once treatment is complete, the stem cells (autologous or allogeneic) are given through a vein or venous access line, just like a blood transfusion. The stem cells migrate to the bone marrow.

In an allogeneic SCT, the person getting the transplant is given drugs such as cyclosporine, methotrexate, tacrolimus, or prednisone to prevent acute graft-versus-host-disease (GVHD; see the section Graft Versus Host Disease below for a more thorough description). In GVHD, the immune cells in the donor’s marrow or cord blood (the graft) attack the patient’s body (the host).

For the next 3 to 4 weeks the patient is given as much supportive therapy as needed. This can include IV nutrition; antibiotics to treat bacteria, viral, and fungal infections; red blood cell and/or platelet transfusions; or other medicines as needed.

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 oncologist or internist. At this point, they only come back to the clinic for regular exams or if they have symptoms that should be checked by their doctor.

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 (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.

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 increased risks of infection and bleeding), nausea, vomiting, loss of appetite, mouth sores, and hair loss.

Complications and side effects that can persist for a long time or that may occur many years after the transplant include:

• graft-versus-host disease (GVHD), which occurs only in allogeneic (donor) transplants 
• 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 with 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 fatal. Usually, immune suppressing drugs can be used to 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.

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 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. Researchers are looking for ways to eliminate the graft-versus-host response while keeping the graft-versus-lymphoma effect.

For more information on these procedures, see the American Cancer Society document, Bone Marrow and Peripheral Blood Stem Cell Transplants.

Last Medical Review: 08/29/2007
Last Revised: 05/12/2009