![]() The risk of both graft rejection (host-versus-graft reaction) and GvHD rises with HLA disparity. However, if the immunologic response is directed against antigens present on normal tissues, it can lead to the destruction of normal organs, described clinically as graft-versus-host disease (GvHD). ![]() This latter characteristic can be a major advantage if the immunologic response is directed against malignant cells, referred to as the graft-versus-leukemia or graft-versus-tumor (GvT) effect, thus potentially eradicating disease and reducing the chance of disease relapse. The distinctive characteristics of allogeneic HSCT are that the stem cell graft is free of contamination by malignant cells and contains immunologically competent lymphocytes that are capable of mediating a reaction against foreign antigens. This chapter focuses primarily on the rationale for the application of allogeneic HSCT in the treatment of malignancy. In addition, allogeneic HSCT is a standard treatment for many immunodeficiency states, metabolic disorders (e.g., Hurler’s syndrome), and defective hematopoietic states (e.g., severe aplastic anemia, thalassemia). Allogeneic HSCT has become a standard treatment option for a variety of hematologic malignancies ( Table 1.1). The first successful reports of clinical bone marrow transplantation, utilized for patients with severe combined immunodeficiency disorders, severe aplastic anemia, and advanced acute leukemias, occurred in the late 1960s and early 1970s. The subsequent determination and understanding of the major histocompatibility complex (MHC) and human leukocyte antigens (HLA) as the major determinants of graft rejection significantly advanced laboratory studies and clinical application of allogeneic HSCT. Intensive research efforts were made in the 1950s and early 1960s to develop methods to reverse the myelosuppressive effects of radiation, including the infusion of bone marrow. The clinical application of HSCT originated in the clinical observations of the severe myelosuppressive effects of radiation among nuclear bomb survivors at Hiroshima and Nagasaki. Hematopoietic stem cells obtained from an identical twin are referred to as syngeneic obtained, and hematopoietic stem cells from someone other than the patient or an identical twin are referred to as allogeneic, which is the focus of this chapter. ![]() Hematopoietic stem cells obtained from the patient him- or herself are referred to as autologous. Hematopoietic stem cells are further characterized according to their source, that is, from whom they are obtained. Stem cells used for HSCT are distinguished as being of hematopoietic origin, as there is growing interest in using more primitive stem cells for regenerative therapy due to their plasticity and unique biologic characteristics. The term “hematopoietic stem cell transplantation” has replaced the term “bone marrow transplantation” (BMT) because hematopoietic stem cells can be derived from a variety of sources other than the bone marrow, including the peripheral blood and umbilical cord blood. Hematopoietic stem cell transplantation (HSCT) is the process and intravenous infusion of hematopoietic stem and progenitor cells to restore normal hematopoiesis and/or treat malignancy. 1.1. Introduction and Historical Perspectives
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