Chapter 35: Immune Reconstitution and Tolerance

Hematopoietic cell transplantation (HCT) remains the only curative treatment option for many patients with hematological malignancies and genetic disorders. Recipients can receive either an autologous or allogeneic graft, which is often dependent upon the primary disease for which transplantation is contemplated. One of the major goals of transplantation is the development of a fully functional immune system. Patients undergoing allogeneic hematopoietic cell transplantation (alloHCT), in particular, have the highest rate of transplantrelated mortality (TRM) due to complications that can result from immunodeficiencies or immune dysregulation that occurs as a consequence of the procedure. These include, but are not limited to, infections, graft‐versus‐host disease (GvHD), autoimmune disorders, and secondary malignancies. Recovery of a fully functional immune system is thus critical for HCT success and improving immune reconstitution is of great clinical interest. This chapter will focus on immune reconstitution following allo‐HCT since immune recovery is more complicated in this setting due to the underlying HLA disparity between the donor and the recipient.