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Allogeneic hematopoietic cell transplantation was first explored in humans in the late 1950s and early 1960s based on observations in animal models that the lethal myelosuppression induced by total-body irradiation (TBI) could be overcome by the infusion of unirradiated bone marrow (1). The initial experience was limited to patients with terminal leukemia or with 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 their primary disease (2). The first successful allogeneic bone marrow transplant was reported in 1968 in a patient with severe combined immunodeficiency (3). Because of this result and the pioneering work of the group in patients with refractory leukemia, the number of allogeneic transplants has increased dramatically over the last decades (4).

Since these initial experiences, allogeneic stem cell transplantation 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 allogeneic transplant was provided primarily by the high doses of chemoradiotherapy administered and that the donor bone marrow simply allowed for hematopoietic recovery in an adequate period of time. It is now apparent that the true success of transplantation relies on a powerful donor immune response against the host malignancy, a phenomenon known as the graft-versus-tumor (GVT) effect.

The primary components of all allogeneic hematopoietic transplants are schematically represented in Fig. 12-1 and include:

  1. Recipient

  2. Donor

  3. Preparative regimen

  4. Stem cell source

  5. Prophylaxis against graft-versus-host disease (GVHD) (including posttransplant immune suppression)

  6. Posttransplant supportive care

Figure 12-1.

Components of allogeneic hematopoietic transplantation.

Successful allografting depends on careful consideration of all these components in an effort to minimize the risks of potentially fatal posttransplant complications.

Despite the known curative potential of allogeneic transplantation, this procedure is performed in only a minority of potentially eligible patients. Broader application of allogeneic stem cell transplantation has been limited by donor availability and the intensity and toxicity associated with the procedure. This chapter reviews the current state of the major components of allogeneic stem cell transplantation, with particular attention to strategies being utilized and evaluated at the MD Anderson Cancer Center (MDACC). The specific role of allogeneic stem cell transplantation with regard to the treatment of specific conditions is reviewed in the chapters dealing with them.

Transplant Recipient

It is estimated that over 20,000 allogeneic transplants have been performed worldwide for a variety of malignant and nonmalignant disorders (5). The International Bone Marrow Transplant Registry (IBMTR), an invaluable resource that collects data from over 400 centers worldwide, allows transplant physicians to see current transplant trends, compare outcomes of different transplant strategies, and do retrospective and prospective studies in hematopoietic stem ...

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