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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.

High-dose chemotherapy and stem cell transplantation are typically performed following several cycles of treatment with anti-myeloma medications (also known as induction therapy). Induction therapy is performed first in order to reduce the tumor burden.

What Are Stem Cells?
Stem cells are a remarkable type of cell that can divide and develop into any one of the three main types of cells found in the blood:
  • Red blood cells, which carry energy-giving oxygen from the lungs to the entire body;
  • White blood cells, important immune cells that play an important role in fighting bacteria and viruses that cause infection; and
  • Platelets, which help blood to clot when bleeding occurs.


Stem cells are found in the bone marrow and in the peripheral blood. Stem cells constitute only a small fraction (less than 1%) of all cells in the bone marrow and an even smaller percentage of cells in the peripheral blood.

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.
Candidates for High-dose Chemotherapy and Stem Cell Transplantation
Many factors must be considered to determine whether a patient is a candidate for high-dose chemotherapy and stem cell transplant. These include the type of myeloma, the stage of disease, how aggressive it is, and the responsiveness of the cancer to prior treatment, as well as a patient's age and general physical condition. Although in the past, transplants were limited to younger patients with good performance status, they are now performed in a more diverse group of patients. Some patients with responsive or stable disease following primary therapy with conventional chemotherapy are candidates for high-dose chemotherapy and stem cell transplantation. In general, patients with good performance status and adequate kidney, lung, and heart function are eligible.

Additional information regarding eligibility for the various types of stem cell transplants is provided in the respective sections on each type of transplant.

Types of Stem Cell Transplants: Overview
There are many types of stem cell transplants. This section defines each of the various types of transplants.

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.
Stem cell transplants are further categorized based on the donor who provides the stem cells.
  • 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
Lastly, there are also several types of transplants under investigation in clinical trials.
The Stem Cell Transplant Process

Stem cell transplantation is a complex process that involves several steps. The process is similar for both autologous and allogeneic stem cell transplants. However, in the case of autologous transplants, the patient will undergo the stem cell collection procedure prior to receiving high-dose chemotherapy and their cells will be frozen and stored until needed. In allogeneic transplants, a stem cell donor will typically undergo the collection procedure just before the transplant will be performed. Since autologous transplants are performed more frequently, we'll focus mainly on this process and indicate where allogeneic transplants are different.
Stem Cell Collection
Most of the stem cells in the human body reside in the bone marrow. Until recently, the only way to obtain stem cells for transplantation was to remove a portion of the bone marrow. However, through recent medical advances, it is now possible to collect stem cells from a person's peripheral blood (that is, from the arm or another site outside the bone marrow). Today, most autologous transplants utilize peripheral blood stem cells (PBSCs). Bone marrow stem cells are more often used in allogeneic transplants, but PBSCs are beginning to be used more frequently.

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.

illustrationCollecting 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.

illustrationOnce 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.

Apheresis is a relatively painless procedure. Patients or donors usually do not need to be hospitalized for apheresis, but must come in for one to three sessions, lasting 2 to 4 hours each, in order to ensure that enough stem cells are collected.

Processing and Cryopreservation

illustration  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.

High-dose Chemotherapy

illustration  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.

illustration  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.


Engraftment and Recovery

During the first few days after transplantation, the reinfused stem cells migrate to the bone marrow and begin the process of producing replacement blood cells, a process called engraftment. The stem cells start to produce new blood cells within 12 to 15 days following infusion. Colony-stimulating factors may be administered during this time to stimulate the process of blood cell production.

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.

Potential Side Effects

Most of the significant potential side effects of stem cell transplantation are a result of the high-dose chemotherapy. Some of the more common temporary side effects include nausea, vomiting, diarrhea, mouth sores (oral mucositis), skin rash, and hair loss. Because the high-dose chemotherapy destroys blood-producing cells in the bone marrow, a patient is susceptible to infection, anemia, and bleeding caused by low blood cell counts until engraftment is complete. Graft-versus-host disease (GVHD) is a serious complication that can occur with allogeneic transplants. In GVHD, immune cells in the transplant attack the patient's cells.

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.

Reviewed by:

Jean-Luc Harousseau, MD
University Hospital, Nantes, France