HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract

Although hematopoietic stem-cell transplantation was originallX conceived more than 50 years ago as a treatment for injury from irradiation and later for cancer, associated problems needed to be solveq before the procedure could be used clinically. Bone marrow, the source of ' hematopoietic stem cells, is not a solid organ but is rather diffuse and not I directly accessible. Furthermore, hematologic cells can initiate immun reactions that may thwart transplantation. Hematopoietic stem cell transplantation is used primarily for hematologic and lymphoid cancers. ' but also for many other disorders

Historical background:

Studies from the mid-20th century demonstrated that massive total I body irradiation causes fatal damage to the gastrointestinal and central!

nervous systems. Lower doses lead to delayed death from hemorrhage: and infection. In animal models, the transplantation of geneticallyj identical (syngeneic) marrow (Lorenz et al., 1951) or the animal's own (autologous) stored marrow (Mannick et al., 1960) averted death. Grafts 1 I from histocompatible littennates also permitted survival. Thel

transplantation of marrow that was not genetically identical (allogeneic) ; to that of the recipient resulted in an immunologic reaction by the donor: lymphocytes against the recipient, causmg inflammation of the target tissues, termed graft-versus-host disease (GVHD). Treatment with! methotrexate suppressed GVHD (Storb et al., 1970). As an alternative to• total body irradiation, cyclophosphamide as a preparative regimen also' I I permitted the engraftment of allogeneic marrow (Santos et al., 1969).