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Bone marrow transplantation was the original term used to describe the collection and transplantation of hematopoietic stem cells, but with the demonstration that the peripheral blood and umbilical cord blood are also useful sources of stem cells, hematopoietic cell transplantation has become the preferred generic term for this process. The procedure is usually carried out for one of two purposes: (1) to replace an abnormal but nonmalignant lymphohematopoietic system with one from a normal donor or (2) to treat malignancy by allowing the administration of higher doses of myelosuppressive therapy than would otherwise be possible. The use of hematopoietic cell transplantation has been increasing, both because of its efficacy in selected diseases and because of increasing availability of donors. The Center for International Blood and Marrow Transplant Research (www.cibmtr.org) estimates that about 65,000 transplants are performed each year.
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THE HEMATOPOIETIC STEM CELL
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Several features of the hematopoietic stem cell make transplantation clinically feasible, including its remarkable regenerative capacity, its ability to home to the marrow space following intravenous injection, and the ability of the stem cell to be cryopreserved (Chap. 1). Transplantation of a single stem cell can replace the entire lymphohematopoietic system of an adult mouse. In humans, transplantation of a few percent of a donor's bone marrow volume regularly results in complete and sustained replacement of the recipient's entire lymphohematopoietic system, including all red cells, granulocytes, B and T lymphocytes, and platelets, as well as cells comprising the fixed macrophage population, including Kupffer cells of the liver, pulmonary alveolar macrophages, osteoclasts, Langerhans cells of the skin, and brain microglial cells. The ability of the hematopoietic stem cell to home to the marrow following intravenous injection is mediated, in part, by an interaction between stromal cell–derived factor 1 (SDF1) produced by marrow stromal cells and the alpha-chemokine receptor CXCR4 found on stem cells. Homing is also influenced by the interaction of cell-surface molecules, termed selectins, on bone marrow endothelial cells with ligands, termed integrins, on early hematopoietic cells. Human hematopoietic stem cells can survive freezing and thawing with little, if any, damage, making it possible to remove and store a portion of the patient's own bone marrow for later reinfusion following treatment of the patient with high-dose myelotoxic therapy.
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CATEGORIES OF HEMATOPOIETIC CELL TRANSPLANTATION
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Hematopoietic cell transplantation can be described according to the relationship between the patient and the donor and by the anatomic source of stem cells. In ~1% of cases, patients have identical twins who can serve as donors. With the use of syngeneic donors, there is no risk of graft-versus-host disease (GVHD), which often complicates allogeneic transplantation, and unlike the use of autologous marrow, there is no risk that the stem cells are contaminated with tumor cells.
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Allogeneic transplantation involves a donor and a recipient who are not genetically identical. Following allogeneic transplantation, immune cells ...