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 (and sometimes radiation) 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 the high-dose treatment. Stem cells are very primitive cells that can create new blood cells.
Blood-forming stem cells used for a stem cell transplant can come from:
- The blood (for a peripheral blood stem cell transplant, or PBSCT)
- The bone marrow (for a bone marrow transplant, or BMT)
- Umbilical cord blood (for a cord blood transplant)
Most stem cell transplants are now PBSCTs.
Types of transplants
There are 2 main types of stem cell transplants. The blood-forming stem cells come from different sources.
Autologous stem cell transplant
In an autologous stem cell transplant, the 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 reinfused into the patient's blood.
This is the most common type of transplant used to treat lymphoma, but it generally isn't an option if the lymphoma has spread to the bone marrow or blood. If that occurs, 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.
Allogeneic stem cell transplant
In an allogeneic stem cell 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.
The use of allogeneic transplants is limited in treating lymphoma because they can have severe side effects that make them hard to tolerate, especially for patients who are older or who have other medical problems. It can also be hard to find a matched donor. About 1 out of 4 transplants for lymphoma is of this kind.
Non-myeloablative transplant (mini-transplant): This is a type of allogeneic transplant in which lower doses of chemotherapy and radiation are used than in a standard SCT. These lower doses do not completely destroy the cells in the bone marrow. When the donor stem cells are given, they 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 less serious side effects.
This type of transplant may be an option for some patients who couldn't tolerate a regular allogeneic transplant because it is too toxic. In fact, a patient can receive a non-myeloablative transplant as an outpatient.
The major side effect is graft-versus-host disease, which can be serious (this is discussed later in this section).
Doctors aren't yet sure exactly how effective these types of transplants are for patients with lymphoma, but studies are now being done to find out.
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 that would require 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 chemo and may include high-dose whole body radiation. The chemo 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. Once treatment is complete, the new stem cells (autologous or allogeneic) are given through a vein (infused), just like a blood transfusion. The stem cells then 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 will likely have very low blood cell counts, so they are 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 later followed by the new platelet production and 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 that can cause life-threatening side effects. 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 stem cell transplant programs may not have experience in certain types of transplants, especially transplants from unrelated donors.
SCT is very expensive (often costing well over $100,000) and often requires a long hospital stay. Autologous transplant is considered a standard treatment for lymphoma under certain conditions, so most medical insurance will cover the cost. Still, some insurance companies may view other types of SCT as an experimental treatment, and they may not pay for those procedures. Even if the transplant is covered by your insurance, your co-pays or other costs could easily amount to tens of thousands of dollars. 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.
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 "Chemotherapy" section of this document), and can be severe. They are caused by damage to the bone marrow and other quickly growing tissues of the body and can include:
- Low blood cell counts (with fatigue and increased risks of infection and bleeding)
- Nausea and vomiting
- Loss of appetite
- Diarrhea
- Mouth sores
- 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 keep this from happening. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.
Long-term side effects: 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, although they may have their own side effects.
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 donor immune 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.
For more information on these procedures, see our document, Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants).
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