Use of hematopoietic stem cell (HSC) transplants for hematologic malignancies, bone marrow failure syndromes (such as aplastic anemia), and disorders caused by inherited HSC defects (such as sickle cell anemia, thalassemia, and immunodeficiency states) is increasing in number each year. Transplantation of genetically “reengineered” hematopoietic stem cells obtained from affected patients may be useful in treating inherited forms of immunodeficiency. Historically, HSCs were obtained from the bone marrow, but now they usually are harvested from peripheral blood after they are mobilized from the bone marrow by administration of hematopoietic growth factors, or from the umbilical cord blood of newborn infants, a rich source of HSCs. In most of the conditions in which HSC transplantation is indicated, the recipient is irradiated or treated with chemotherapy to destroy the immune system (and sometimes, cancer cells) and to “open up” niches in the micro-environment of the marrow that nurture HSCs, thus allowing the transplanted HSCs to engraft. Two major problems complicate this form of transplantation and distinguish it from solid organ transplants: graft-versus-host disease and immune deficiency.
GVHD occurs when immunologically competent cells or their precursors are transplanted into immunologically crippled recipients, and the transferred cells recognize alloantigens in the host and attack host tissues. It is seen most commonly in the setting of HSC transplantation but, rarely, may occur following transplantation of solid organs rich in lymphoid cells (e.g., the liver). On receiving allogeneic HSCs, an immunologically compromised host cannot reject the graft, but T cells present in the http://ebooksmedicine.net