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After studying this chapter, you should understand:

  • The clinical applications and complications of hematopoietic stem cell transplantation.

  • The major types of hematopoietic stem cell transplantation.

  • The genetics of allogeneic hematopoietic stem cell transplantation.

  • The causes of graft rejection and graft failure.

  • The pathogenesis of graft-versus-host disease and the graft-versus-tumor effect.

The era of hematopoietic stem cell transplantation (HSCT) began in the 1950s, when pioneering studies by E. Donnall Thomas, James Till, and Ernest McCulloch demonstrated the ability of unfractionated bone marrow cells to “rescue” animals from hematopoietic failure induced by otherwise lethal doses of radiation. Such studies had profound implications and consequences for basic research, because they proved the existence of multipotent hematopoietic stem cells and provided a powerful new experimental tool for studying the immune system.

From very early days, it was evident that HSCT also had enormous therapeutic potential but was prone to cause serious and all too frequently fatal complications. HSCT remains as close to a high-wire act as exists in medicine, one in which patients receive potentially lethal doses of chemotherapy and/or radiation. However, as we will discuss, advances in stem cell biology, immunology, and pharmacology have allowed the development of more effective, less toxic HSCT strategies. As a result, HSCT is now being used to treat an increasing number of disorders and a broader spectrum of patients than ever before. This chapter serves as an overview of some of the salient features of this fascinating, rapidly evolving area of hematology.


HSCT has proven to be effective in the following clinical settings:

  • Correction of genetic and acquired defects in hematopoietic stem cells (HSCs). Until the dream of gene therapy for germline defects is realized (an advance that now seems tantalizingly close with the recent development of CRISPR technology), HSCT is often the only hope for those suffering from severe genetic disorders that affect the function of the HSC or its progeny. Replacing the defective HSCs of the patient with HSCs obtained from a normal donor can cure such diseases. HSCT has been used to treat many genetic diseases, including those affecting lymphocytes (e.g., severe combined immunodeficiency, X-linked agammaglobulinemia), red cells (e.g., severe thalassemia, sickle cell disease), and monocytes/macrophages (e.g., Gaucher disease).

  • Support for high-dose cancer treatment. The dose-limiting toxicity of radiotherapy and many conventional chemotherapy agents is bone marrow failure due to ablation of HSCs. HSCT overcomes this limitation by providing the patient with healthy HSCs, which can completely reconstitute hematopoiesis and the immune system over a period of weeks to months.

  • Generation of graft-versus-tumor effect. When a recipient receives HSCs from another individual who is not an identical twin, the transplanted HSCs give rise to a “new” immune system that may recognize the patient’s tumor as non-self and mount an immune response against it. It is now clear that this graft-versus-tumor effect is ...

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