Patients Starting Treatment:
Treatment Options - Stem Cell Transplantation
Stem Cell Transplantation
Stem cell transplantation, performed as support for high-dose chemotherapy, is a treatment option for many patients with myeloma. Studies have shown that this treatment improves both the response rate and survival in myeloma over that obtained with other treatments.
The Center for International Blood and Marrow Transplant Research (CIBMTR) estimates that approximately 4,700 stem cell transplants of various types were performed in patients with myeloma in North America in 2003 (CIBMTR, 2005).*
The International Myeloma Working Group released a Consensus Statement, recommending the use of allogeneic reduced-intensity conditioning (allo-RIC) only in the context of clinical trials. Click here to read the abstract.
What It Is
A stem cell transplant is a procedure that is used in conjunction with high-dose chemotherapy, which is frequently more effective than conventional chemotherapy in destroying myeloma cells. Because high-dose chemotherapy also destroys normal blood-producing stem cells in the bone marrow, these cells must be replaced in order to restore blood cell production.
The first step in the process of stem cell transplantation is the collection of stem cells from a patient or a donor. When a patient's own stem cells are used, they are frozen and stored until needed. Stem cells can be collected from a donor when they are needed. The patient then receives high-dose chemotherapy and the stem cells are infused into the patient's bloodstream. The stem cells travel to the bone marrow and begin to produce new blood cells, replacing the normal cells lost during high-dose chemotherapy.
Without stem cells, blood cell production would cease. Therefore, stem cells that are lost during high-dose chemotherapy are replenished with a stem cell transplant, thus restoring blood cell production.
Additional information regarding eligibility for the various types of stem cell transplants is provided in the respective sections on each type of transplant.
First, stem cell transplants are defined by by the source of the stem cells.
Bone marrow transplants are those that are obtained from the bone marrow. However, they are rarely performed today in myeloma because of the ability to collect stem cells from the peripheral blood (see below). Bone marrow transplants are sometimes used if insufficient numbers of stem cells can be obtained from the peripheral blood.
Peripheral blood stem cell (PBSC) transplants are obtained from the peripheral blood. PBSC transplants are now performed much more often than bone marrow transplants because they are easier to collect, they provide a more reliable number of stem cells, the procedure puts less strain on the donor's system, and the patient recovers more quickly
Cord blood transplants refer to transplants where the stem cells are obtained from umbilical cord blood. Historically they have not been used frequently due to limited numbers of stem cells that can be collected from each umbilical cord. Recently, however, exciting new data have been generated using multiple cord blood units from more than one donor.
Autologous stem cell transplants (autografts) refer to stem cells that are collected from an individual and given back to that same individual. Most stem cell transplants in myeloma are autologous transplants.
Allogeneic stem cell transplants (allografts) refer to stem cells that are taken from one person and given to another. Currently, these types of transplant are performed much less frequently in myeloma in the US and are usually performed in the context of clinical trials.
Syngeneic stem cell transplants refer to stem cells that are taken from an identical twin of the recipient. These types of transplants are quite rare
A tandem autologous transplant, also known as a double autologous transplant, requires the patient to undergo two autologous stem cell transplants within 6 months.
A mini (nonmyeloablative) allogeneic transplant involves the use of moderately high-dose chemotherapy in combination with an allogeneic stem cell transplant.
Collecting stem cells from bone marrow. Collecting, or "harvesting," bone marrow is usually done in a hospital operating room under general anesthesia. Using a needle and syringe, a surgeon will take bone marrow from several different areas of the hip bone (pelvis). The bone marrow, which appears as a thick red liquid, is typically frozen and stored until high-dose chemotherapy is completed.
Collecting stem cells from peripheral blood. Harvesting stem cells from the blood takes approximately a week and has certain advantages over collecting stem cells from bone marrow. No general anesthesia is needed for this collection method, and it often can be done in an outpatient setting so no overnight hospital stay is necessary.
Because most stem cells reside in the bone marrow, it is necessary to move stem cells from the bone marrow to the bloodstream prior to their collection. This procedure is called mobilization.
A commonly used mobilization technique is to administer a medication specifically designed to increase the number of stem cells in the blood. This medication is called a colony-stimulating factor, or "growth factor," and is usually injected under the skin, much like an insulin injection for diabetes.
Once a sufficient number of stem cells are mobilized from the bone marrow into the bloodstream, the stem cells are collected using a non-surgical procedure called apheresis. Apheresis is a procedure in which blood is removed from the patient or a donor via a needle in the arm, similar to a blood donation. Patients may also have blood removed via a central line in a vein in the chest. The blood is then circulated through a cell separator, whereby the white blood cell component enriched for stem cells is separated out. The rest of the blood flows back into the patient or donor.
After the bone marrow or peripheral blood stem cells are collected from the patient, they are processed in the laboratory, cryopreserved (frozen), and stored until needed. Allogeneic stem cells typically do not require this step since they are collected just prior to transplant.
After the bone marrow or stem cells are collected, or at some later date, the patient will receive high-dose chemotherapy. The higher doses of chemotherapy are designed to destroy cancer cells more effectively than standard chemotherapy. Depending on the type of cancer and other factors, some patients may receive one or more treatments of high-dose chemotherapy, possibly in combination with radiation therapy, over a period of several days. This combination of treatments is also referred to as a conditioning regimen. These treatments, in addition to killing cancer cells, also destroy the blood-producing cells in the bone marrow, hence the need for the stem cell transplant. The chemotherapy drug melphalan is the most commonly used conditioning regimen in myeloma. Some patients may receive their high-dose chemotherapy on an outpatient basis.
Within a few days after completing the high-dose chemotherapy, the stored blood or bone marrow (or recently harvested allogeneic) stem cells are transplanted, or infused, into the patient's bloodstream. The infusion process is similar to a blood transfusion, and can be done on an outpatient basis in some cases. The frozen bags of bone marrow or blood cells are thawed in a warm water bath and infused into a vein over a period of 2 to 4 hours. The infused stem cells travel through the bloodstream and settle in the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets.
Until engraftment is complete, a transplant recipient is susceptible to infection, anemia, and bleeding caused by low blood cell counts. Therefore, special precautions are necessary during recovery. Patients may be given red blood cell and platelet transfusions during the recovery period to help prevent anemia and bleeding. For the first 2-4 weeks after the transplant, patients are very susceptible to developing infections. This is because the effects of the high-dose chemotherapy and the loss of blood cells weaken the body's immune system. Antibiotics are often prescribed to help prevent infection.
The doctors, nurses, and other members of the healthcare team will do everything possible to ensure a successful recovery. However, patients and their family or caregivers are also active participants in the recovery process. Patients are asked to come in for frequent check-ups and tests during the early recovery period, which typically lasts about 6 weeks.
Patients who receive part of their transplant care on an outpatient basis need to stay near the treatment center so that they can be closely monitored. Some patients are admitted to the hospital during the recovery period. Patients receiving autologous transplants can expect to stay in the hospital for about 2 weeks or less following a stem cell transplant. On the average, it takes about 2 to 3 months to recover normal physical performance after an autologous procedure. However, it can take as long as a year for a patient to get back to his or her normal routine.
Because there is greater potential for adverse events following an allogeneic stem cell transplant, the recovery period is longer than that of an autograft. Allograft recipients can expect to stay in the hospital for about 4 to 6 weeks (longer in cases of graft-versus-host disease [GVHD]), with a recovery period of up to 6 months, depending on whether any late complications occur.
The severity of side effects such as nausea and vomiting can be reduced by medication. The medication palifermin (Kepivance™, Amgen) may be used to help reduce the duration and severity of oral mucositis. Patients are very closely monitored during high-dose chemotherapy, with daily weight measurements, as well as frequent measurements of blood pressure, heart rate, and temperature.
*Since publication of these recommendations, several trials have demonstrated superiority of tandem autologous SCTs over single autologous SCTs with regard to event-free survival.