Overview and Types of Stem Cell Transplantation:

Stem cell transplantation is a procedure that can restore marrow function for patients who have had severe marrow injury or abnormalities of the immune system. Marrow injury can occur because of primary marrow failure, destruction or replacement of marrow by disease, or intensive chemical or radiation exposure. Fast Facts About Stem Cell Transplantation { Since blood and marrow are both good sources of stem cells for transplantation, the term “stem cell transplantation” has replaced “bone marrow transplantation” as the general term for this procedure. The abbreviation “BMT” is now used to represent blood and marrow transplantation. There are many terms for transplantation, including bone marrow transplantation (BMT), marrow or cord blood transplantation or hematopoietic cell transplantation (HCT). These are all different names for the same procedure. { Today, the stem cells used for transplantation can come from marrow, peripheral blood or umbilical cord blood. Peripheral blood is now the most common source of stem cells for transplantation. { The use of cord blood stem cells for transplantation is about two decades old. Compared to peripheral blood or marrow, cord blood is a relatively new source of cells, especially for adults. { “Reduced-intensity” allogeneic stem cell transplantation is an option for certain patients who have a stem cell donor. Compared to a fully myeloablative allogeneic transplant (referred to as a “standard” allogeneic transplant throughout this booklet; see page 24), a reduced-intensity transplant delivers lower doses of chemotherapy drugs and/or radiation to the patient in preparation for the transplant. The success of reducedintensity transplantation depends upon the graft-versus-tumor (GVT) effect of the donor stem cells, rather than on high doses of chemotherapy. This approach may benefit older and sicker patients and other selected patients. { The donor cells are called the “graft.” When the donor cells attack the diseased cells, it is called the “graft-versus-disease (GVD) effect.” { Attempts to use the marrow cells of a healthy individual to restore the lost marrow function of another person began about 65 years ago. { The basis for stem cell transplantation is that all blood cells and immune cells arise from stem cells in marrow. At the turn of the 20th century, scientists began to formulate the idea that a small number of cells in the marrow might be responsible for the development of all blood cells. They began to refer to them as “stem cells.” The scientific exploration of marrow transplantation as a form of treatment began at the end of World War II. Blood and Marrow Stem Cell Transplantation I page 7 { The source for the earliest transplants was the marrow of a healthy donor who had the same tissue (human leukocyte antigen [HLA]) type as the patient. Usually, the source was a brother or sister. { When a patient needs an allogeneic transplant (stem cells from a donor), his or her doctor turns to a registry of donors—a list of people who are willing to donate to any patient in need—and of donated umbilical cord blood. The Be The Match Registry®, operated by the National Marrow Donor Program®, is the world’s largest listing of volunteer donors, more than 9.5 million. Using information about the patient’s HLA type, a computer program is used to scan the database of HLA types of volunteer donors. Autologous Stem Cell Transplantation. This type of transplantation involves the use of a patient’s own stem cells. The stem cells are collected from marrow or blood, then frozen. The thawed cells are returned to the patient after he or she has received intensive chemotherapy and/or radiation therapy for his or her disease. The primary purpose of an autologous transplant is to allow the patient to be given high doses of chemotherapy with or without radiation that would otherwise be too toxic to tolerate because the marrow would be severely damaged. Such high doses of treatment can sometimes overcome resistance of the disease to standard doses of chemotherapy. Autologous transplantation requires that an individual have sufficient numbers of healthy stem cells in the marrow or blood. For example, in patients with acute leukemia, remission must be achieved before the patient’s marrow or blood is harvested and frozen for later use (see page 23). This procedure is also referred to as “autologous stem cell infusion,” because stem cells are not being transferred from one person to another. Since the stem cells are the recipient’s own, graft-versus-host disease (GVHD) is rarely a problem. However, the patient’s immune system does require time to recover after the procedure, and risk of relapse of the person’s disease may be higher. Standard Allogeneic Stem Cell Transplantation. This type of transplantation involves the use of donor stem cells. The donated stem cells can come from a related or unrelated donor. Siblings have the potential to match the patient's tissue type most closely, because the patient and the sibling donor have received their genes from the same parents. However, siblings do not always have closely matched tissue types. The term “unrelated donor" (URD) is sometimes used to describe a donor who is not a blood relative. An unrelated donor is found by searching registries of volunteer donors for an individual who happens to be identical or very similar in tissue type to the patient. Transplant doctors can test to determine the degree of compatibility before a decision is made to use a particular donor. Compatibility is assessed by laboratory tests that identify the tissue type of both donor and recipient, called the page 8 I 800.955.4572 I www.LLS.org “human leukocyte antigen” (HLA) type. Stem cells from cord blood may also be a source for allogeneic transplants for certain patients (see page 19). When a transplant is successful, the donor stem cells can restore normal marrow, and may provide the only long-term cure of the patient’s disease. The immune system and the blood system are closely linked and cannot be separated from each other. Because of this, allogeneic transplantation means that not only the blood system but also the immune system of the donor is transferred to the recipient. As a result, these effects are possible: { Immune rejection of the donated stem cells by the recipient (host-versus-graft effect) { Immune reaction by the donor cells against the tissues of the recipient (graft-versus-host disease [GVHD]). Before a standard allogeneic transplant, patients receive high doses of chemotherapy and sometimes radiation therapy. This treatment is called a “conditioning regimen” or “preparative regimen,” and it destroys the cancer cells. It also suppresses the patient’s immune system; therefore, the immune system is less able to attack the transplanted donor stem cells. One of the benefits of an allogeneic transplant is that the donor immune system can recognize remaining cancer cells that have survived even high doses of chemotherapy, with or without radiation, and kill them, helping to prevent disease relapse. A critical benefit of allogeneic transplantation is the generation of a graft-versusdisease (GVD) effect that may be even more important than the very intensive therapy administered to destroy cancer cells. This effect is a result of the donor’s immune system “recognizing” the patient’s cancer cells and eliminating them. Unfortunately, despite appropriate tissue matching, similar donor cells may also react against the patient’s normal cells and generate a potentially serious condition called “graft-versus-host disease” (GVHD). The use of autologous stem cells has neither the drawbacks of GVHD nor the advantages of a GVD effect. The immune reaction, or GVHD, is treated by giving drugs to the recipient after the transplant to reduce the ability of the donated immune cells to attack and injure the patient’s tissues (see Graft-Versus-Host Disease, page 31). Over time, the new immune system grown by the donor cells may develop tolerance to the host (the patient), and the immunosuppressing medications can be weaned and eventually stopped in some cases. Reduced-Intensity Allogeneic Stem Cell Transplantation.