Hematopoietic stem cells are the "mother cells" from which all blood cells evolve (hematopoietic cells). The greatest concentration of stem cells is found in the bone marrow (the soft, spongy tissue found in large bones). Therefore, when doctors harvest bone marrow for transplant, it is really the stem cells in the bone marrow that they are collecting. However, stem cells can also be found from other sources. In addition to the bone marrow, hematopoietic stem cells can also be found in the peripheral blood and in the umbilical cord. Peripheral blood is the blood found in the body throughout the bloodstream, while cord blood is found in a baby’s umbilical cord.
The goal of autologous and allogeneic transplants is to exploit the concept of dose intensity. In other words, these transplants are given after the use of high dose chemotherapy. The transplants require collection of sufficient numbers of hematopoeitic stem cells for reconstitution of hematopoeisis and immunity. Both types of transplant are most commonly used for treatment of malignancies. The following section defines autologous and allogeneic transplants and attempts to outline their advantages, disadvantages, and implications.
Autologous hematopoeitic stem cell transplants involve the reinfusion of the patient’s own hematopoeitic stem cells following chemotherapy or radiation therapy, usually after cryopreservation. Cryopreservation keeps the stored cells viable for more than five years. Chemotherapy is needed to eradicate malignant cells or tumors resistant to less intensive treatment options. The procedure is most successful in patients with malignancies shown to be responsive to conventional treatment immediately prior to the transplant regimen.
Autologous transplants are possible if the disease afflicting the bone marrow is in remission or if the condition does not involve bone marrow (e.g. breast cancer, ovarian cancer). Ideally, the hematopoeitic cells should be collected when the patient’s bone marrow is normally cellular and the blood and marrow do not contain malignant cells. However, if some malignant cells still remain in the blood after hematopoeitic cells are removed from the patient’s own body (transplant procedure), this blood must be “purged,” and the lingering malignant cells must be removed. Adequacy of the harvested cells is the single critical factor in this process.
Autologous transplants are used to treat a wide variety of malignancies. This type of transplant has been proven to benefit intermediate grade lymphoma, Hodgkin’s disease, acute lymphoblastic leukemia, and acute myelogenous leukemia. It has also shown to cause improvements in survival in myeloma patients. Additionally, it has been shown to benefit breast and ovarian cancers, germ cell cancers, low grade lymphomas, and pediatric solid tumors; these malignancies are more controversial, but are currently being actively studied. Autologous transplants have recently been explored as a method to treat diverse diseases such as multiple sclerosis or scleroderma.
Although they are proven effective, autologous transplants do not always prevent relapse. Some factors that are known to predispose patients to relapse include higher volume residual tumor, tumor types not known to exhibit a steep dose-killing relationship, or treatment of patients at high risk for toxicities from the proposed treatment regimen.
Autologous Stem Cell Sources
Recipient Age - Autologous Transplants
Yellow -> 20 years
Advantages of autologous transplants
There are many advantages to using autologous transplants, but an autologous transplant may not always be feasible. Autologous transplants lead to decreased infection because the patient is being infused with his or her own blood. Additionally, there is no need for immunosuppression, and transplants do not require histocompatibility matching. For this same reason, grafts rejection rarely occurs, and the graft will not produce Graft vs. Host disease. What is more, autologous blood is readily available, and immune reconstitution is more rapid than after allogeneic. Treatment related mortality is lower than 5% in most studies (stats).
Disadvantages of autologous transplants
Despite the many advantages of autologous transplants, they are not always the best choice for hematopoeitic stem cell transplants. For instance, malignant cells may contaminate autologous stem cell products. The likelihood that the cells would be contaminated varies with the diagnosis and disease stage. It happens less frequently in peripheral blood as compared to bone marrow but any remaining clonogenic tumor cells can contribute to relapse. Therefore, autologous transplants cannot be used for genetic or acquired diseases in which the hematopoeitic cells are injured or defective. Autologous transplants also fail to confer the same immune mediated GvM effect that allogeneic transplants have. They have a higher risk of relapse.
Allogeneic hematopoeitic stem cell transplants are obtained from another individual, a related or matched, unrelated donor. Donor registries use the HLA system to match donors and recipients. The transplants can be obtained from the donor’s bone marrow or peripheral blood. In order to prevent rejection of the donor’s hematopoeitic stem cells, the patient must undergo pre-transplant immunosuppresion as a “preparative regimen.” After the engraftment of the donor-derived stem cells, they are infused into the recipient where these cells reconstitute hematopoeisis and immunity. Following transplant, recipients are considered chimeras with hematopoeitic and immune cells derived from the donor.
Allogeneic transplants are used to treat bone marrow failure states, hemoglobinopathies, immune deficiencies, and inborn errors of metabolism by establishing a new normally functionally hematopoeitic and immune system. The transplants have also been successfully used in humans for the treatment of children with severe combined immune deficiency. Allogeneic transplants are usually used in younger patients.
Allogeneic Stem Cell Sources
Recipient Age - Allogeneic Transplants
Yellow ->20 years
Allogeneic transplants are free of contaminating tumor cells. Furthermore, they confer an immune mediated graft-versus-malignancy (GVM) effect, or the ability of the donor-derived lymphoid T cells to recognize residual cancer cells. These donor-derived lymphoid cells may react against and eradicate malignant cells that survive high dose cytotoxic therapy. Patients that undergo allogeneic transplants have a substantially lower relapse rate as compared to purged autologous transplant patients.
Disadvantages of allogeneic transplants
Allogeneic transplants could cause regimen-related organ toxicity, graft failure, or graft-versus-host disease (GVHD). Also, immune reconstitution is slower and treatment related mortality is higher than in autologous transplants. Although there is a lower risk of relapse, high doses of immunosuppressive therapy have been associated with an increased risk of relapse and withdrawal of immunosuppressive treatment can occasionally produce remission in patients relapsing after transplantation.
Autologous or allogeneic transplant?
Selection of whether to give a patient an autologous or allogeneic transplant depends on many factors including type of malignancy, age of recipient, availability of a suitable donor, ability to collect a tumor free autograft, the stage and status of the disease, and whether or not the malignancy is susceptible to GVM effects
Syngeneic transplants are between genetically identical twins. There is not need for immunosuppression or HLA typing, but the risk of relapse after high dose therapy and hematopoeitic transplantation is increased in syngeneic transplants compared to allogeneic transplants
Hematopoeitic stem cells circulate in low frequency in the peripheral blood; they serve as an alternative source of hematopoeitic cells for transplant. These peripheral cells must be “mobilized” from the marrow by administering granulocyte stimulating hematopoeitic growth factors alone or in combination with chemotherapy.
Advantages of peripheral blood stem cell transplant
Peripheral blood transplants are now routinely used because they engraft more rapidly than bone marrow transplants. In addition, peripheral blood transplants have a lower frequency of tumor cell contamination than bone marrow harvests (for autologous transplants). Therefore, peripheral blood stem cell transplants can be performed in patients in whom marrow harvesting is not feasible.
Umbilical cord blood and placental blood have recently been proposed as alternative sources of hematopoeitic stem cells for transplantation from related or unrelated donors. They serve as a rich source of hematopoeitic stem cells and progenitor cells. Neither umbilical cord stem cells nor placental blood stem cells are considered embryonic stem cells.
Using umbilical cord blood for transplantation provides the patient with a certain number of advantages. Because the T-lymphocytes (part of the immune system that causes graft-versus-host disease) are not completely functional in this early stage of life, cord blood allows for transplantation into patients that are partially HLA mismatched. In addition, cord blood is easily stored and ready to use within two weeks.
Disadvantages to using umbilical cord blood
Umbilical cord blood is not always the best choice for transplantation. The blood from the umbilical cord could be immunologically immature, making it harder for the patient to reconstitute his/her immune system. Additionally, it takes longer for cord blood cells to engraft (begin to grow and create new blood cells and an immune system). Until these cells engraft, the patient is at a high risk for infection. After transplant, there remain no backup cells from same cord blood unit. If the patient relapses, they may need a second donation. What is more, it is a newer treatment approach for transplant, so doctors do not have as much info about patient’s long-term results.
Uses of umbilical cord blood
Due to the limited amount of blood that can be collected from each umbilical cord, this type of transplant is used more often in smaller children. Nevertheless, umbilical cord blood is used for many other types of transplants and many unrelated cord blood registries have been established. Today, the National Marrow Donor Program (NMDP) registry includes more than 50,000 cord blood units. The odds that a child will need to use his or her own stem cells by age 21 for current treatments are about 1/2700 and the odds that a family member would need to use those cells are about 1/1400. The transplant process is the same as for marrow and peripheral blood cell transplants.