The usual doses of chemotherapy drugs can cause serious side effects in quickly dividing tissues such as the bone marrow (where new blood cells are made). Even though higher doses of these drugs might be more effective in treating Hodgkin disease, they are not given because the severe damage to the bone marrow would cause life-threatening 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 (sometimes along with radiation therapy). After treatment is finished, the patient receives a transplant of blood-forming stem cells to restore the bone marrow.
High-dose chemotherapy and stem cell transplant may be used:
- When Hodgkin disease doesn't go away completely after standard treatment with chemotherapy and/or radiation therapy
- When Hodgkin disease seems to go away completely after chemotherapy and/or radiation, but then comes back at some later time
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 Bone marrow transplants were more common in the past, but they have largely been replaced by PBSCTs.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: autologous and allogeneic. The source of the blood-forming stem cells is different.
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 then are given back to the patient by infusion into the patient's blood.
This is the more common type of transplant for Hodgkin disease.
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) 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.
Sometimes umbilical cord blood stem cells are used. These cells come from blood drained from the umbilical cord and placenta after a baby is born, which is rich in blood stem cells. These are more often a source of cells for transplants in children.
Allogeneic transplants may be more likely to rid the body of lymphoma cells, but they are also more likely to cause serious complications that could be life-threatening. In treating Hodgkin disease, an allogeneic transplant is generally used only if an autologous transplant has already been tried without success. Sometimes a special type of allogeneic transplant, called a non-myeloablative (reduced intensity) transplant, may be used.
Non-myeloablative transplant: This is a special type of allogeneic transplant in which the patient receives lower doses of chemotherapy and radiation that do not completely destroy the cells in the 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 (this is called the graft-versus-lymphoma effect). Because this type of transplant uses less chemo and radiation, it is also known as a mini-transplant or reduced-intensity transplant. It may be an option for some patients who couldn't tolerate a regular allogeneic transplant because it is too toxic.
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 and have less serious side effects. In fact, a patient can receive a non-myeloablative transplant as an outpatient.
The major side effect is graft-versus-host disease, which may damage the patient's body tissue (this is discussed in more detail below).
Doctors aren't yet sure exactly how effective these types of transplants are for patients with Hodgkin disease, but studies are now being done to find out.
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 they are going to be treated in the hospital, the person is usually admitted to the hospital the day before chemotherapy is to begin. He or she will usually stay in the hospital until the stem cells have started to work, making new blood cells again, which often takes several weeks.
If the transplant is done as an outpatient procedure, patients and 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. Once treatment is complete, the stem cells (autologous or allogeneic) are given through a vein, 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. This is known as graft-versus-host disease or GVHD. 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 protected in 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 their regular exams or if they have symptoms that should be checked by their doctor.
Practical points
A stem cell transplant 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 well over $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
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
- Diarrhea
- Loss of appetite
- Mouth sores
- 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.
Long-term side effects: Some complications and side effects can last for a long time or may occur many years after the transplant. These include:
- Graft-versus-host disease, which occurs only in allogeneic transplants (see next paragraph)
- 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 the donor's immune system. The donor immune system then may "see" 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 tire easily 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 can 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 the American Cancer Society document, Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants).
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