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KEY CONCEPTS

  • The numbers of allogeneic hematopoietic stem cell transplantation (HCT) are increasing over time, with an increasing use of alternative donors, and with increasing use of reduced-intensity conditioning (RIC).

  • Myeloablative conditioning (MAC) for HCT is associated with a lower risk of relapse compared with RIC, but it is also associated with a higher risk of nonrelapse mortality (NRM).

  • Age, performance status, and HCT-specific comorbidity index are some of the predictors of NRM and are taken into consideration along with the risk of relapse of the underlying disease, when deciding about conditioning intensity.

  • Relapse of the underlying disease is the leading cause of deaths after allogeneic HCT, while graft-versus-host disease (GVHD) and infections are the leading causes of NRM after allogeneic HCT.

  • Risk of relapse may be reduced with the use of maintenance therapy after allogeneic HCT, which is an area of active investigation.

  • Novel GVHD prophylaxis strategies are being explored to reduce the risk of GVHD and its associated morbidity and mortality.

INTRODUCTION

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative approach for a variety of malignant and nonmalignant disorders. With the development of novel techniques of transplantation including the refinement of conditioning regimens and improved management of transplantation-associated toxicities, increasing numbers of patients with advanced age and/or comorbidities are now being transplanted. More than 9000 allogeneic HCTs were performed in the United States in 20181; about 30% of patients were age 60 years or older and 6% were 70 years or older.2 This chapter reviews the current state of the allogeneic HCT in general, with particular attention paid to strategies used at MDACC. The in-depth discussion of specific diseases and their indications for HCT can be found in their respective chapters.

HISTORICAL BACKGROUND

Research in the field of HCT intensified after the unfortunate events of nuclear bombing in 1945,3 with one of the first HCT in humans performed in the late 1950s. The initial attempts at transplantation of bone marrow (BM) from fetal or adult cadavers in six patients with terminal conditions was unsuccessful without engraftment. However, it did provide important safety data about the infusion of BM with no case of pulmonary emboli.4 A few years later, syngeneic BM transplantation (BMT) in two children with acute lymphoblastic leukemia (ALL) after lethal dose of total-body irradiation (TBI) led to successful engraftment, but the conditioning intensity was insufficient to prevent disease relapse.5 Thereafter, modifications were made to intensify the conditioning regimen before transplantation. There was a vigorous interest in BMT in the early 1960s, with occasional success stories, but interest waned owing to extremely poor outcomes, engraftment in less than 40% of cases, and mortality in about 75% of patients.6 This was partly related to the lack of knowledge about graft-versus-host disease (GVHD), which was not recognized until the mid-1960s,7 and inadequate understanding of the human leukocyte antigen (HLA) system—the ...

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