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For patients with hematologic malignancies, allogeneic stem cell transplantation (alloSCT) provides potentially curative therapy over standard therapeutic approaches in patients whose disease is incurable with standard chemotherapy. With the development of novel techniques of transplantation, including reduced-intensity conditioning (RIC) and management of transplant-associated toxicities, increasing numbers of patients with advanced age or comorbidities can undergo this potentially lifesaving procedure. According to the most recent statistics from the Center for International Blood and Marrow Transplant Research (CIBMTR), a consortium that collects data from over 400 transplant centers worldwide, over 9,000 patients received alloSCT in 2011, up from 7,500 in 2001 (1). Given the increasing frequency of stem cell transplants worldwide, practitioners need to be familiar with the key concepts regarding the indications, procedures, and management of this technique. This chapter reviews the current state of alloSCT, with particular attention to strategies utilized at the MD Anderson Cancer Center (MDACC). The specific indications for alloSCT are briefly discussed, but a more in-depth discussion of indications is found in chapters covering specific disease states.


Background and Rationale


Allogeneic stem cell transplantation was first explored in humans in the late 1950s and early 1960s based on observations in animal models that lethal myelosuppression induced by total-body irradiation (TBI) could be overcome by the infusion of healthy, untreated bone marrow (2). The initial experience was limited to patients with terminal leukemia or severe marrow failure states resulting from radiation exposure or disease. Almost all of these early patients died from complications of graft failure, graft-versus-host disease (GVHD), infections, or primary disease (3). The first successful allogeneic bone marrow transplant was reported in 1968 in a patient with severe combined immunodeficiency (4). Since these initial experiences, alloSCT has been used to treat thousands of patients with historically incurable diseases.


In the early days of the field, it was thought that the curative effect of alloSCT was provided primarily by the high doses of chemotherapy and radiation administered, and that the donor bone marrow simply allowed for hematopoietic recovery in an adequate period of time. However, it was later determined that the stem cell graft, and associated donor immunity, was responsible for the curative potential of alloSCT. This graft-versus-tumor (GVT) effect was first demonstrated in a landmark study published in 1990 (5). This study showed decreased rates of relapse in patients who experienced GVHD, an auto-immune syndrome associated with human leukocyte antigen (HLA) mismatch between the donor and recipient. Patients who experienced GVHD had lower rates of relapse compared to patients who either did not experience GVHD or received T-cell-depleted/syngeneic grafts. Patients with GVHD had a strong GVT effect, suggesting that similar mechanisms underlie the immunologic biology of both processes. However, it does not appear that GVHD is necessary for the GVT effect. Separating the adverse effects of GVHD from the therapeutic effect of the GVT effect remains the ...

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