Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures. Immune reconstitution post-HSCT occurs in several phases, innate immunity being the first to regain function. The slow T cell reconstitution is regarded as primarily responsible for deleterious infections with latent viruses or fungi, occurrence of graft-versus-host disease, and relapse. Here we aim to summarize the major steps of the adaptive immune reconstitution and will discuss the importance of immune balance in patients after HSCT.

Gene transfer into hematopoietic stem cells reduces HLH manifestations in a murine model of Munc13-4 deficiency

“…Slow T-cell reconstitution is regarded as being primarily responsible for poor infection control, the occurrence of graft-versus-host disease, and relapse after HSCT. 24 Hence, at a later step and according to results achieved in the separate trials, patients could be transplanted with gene-corrected autologous HSCs as a curative long-term treatment and with gene-corrected autologous T cells.…”

Reconstitution of adaptive immunity after umbilical cord blood transplantation: impact on infectious complications

“…T-cell recovery after alloHSCT proceeds along two different pathways that act in parallel but follow distinct kinetics: (I) homeostatic peripheral expansion of mature T cells (termed the "thymic-independent pathway"); and (II) naive T-cell neo-production from donor hematopoietic progenitor cells through the thymus (termed the "thymicdependent pathway") ( Figure 1) (12,19).…”

“…Immune reconstitution of B cells after alloHSCT is markedly different from that of T cells (12,66 ) pool may take several (up to 5) years (11,67). It occurs upon antigen exposure but also requires CD40 signals as well as cytokine stimulation from CD4 + T cells (follicular B helper T cells).…”

“…Studies reported that delayed T-and B-cell recovery associated with increased risks of post-transplant opportunistic infections and transplant-related mortality (6)(7)(8)(9)(10)(11). Reconstitution of adaptive immunity after alloHSCT is a complex and slow process that can be influenced by several factors, such as recipient age, type of donor (related/unrelated, HLA-matched/HLA-mismatched), type of conditioning (myeloablative/reduced intensity; including or not radiation therapy), ex vivo or in vivo T-cell depletion of the graft, type of graft-versus-host disease (GVHD) prophylaxis, as well as occurrence and treatments of GVHD (12). Some impact…”

Safety and immunogenicity of conjugate quadrivalent meningococcal vaccination after hematopoietic cell transplantation

“…2,3 The immunogenicity of the MCV4 vaccine among adult hematopoietic cell transplant (HCT) recipients has not been prospectively studied. Although these patients usually recover immunoglobulin G1 levels within a few months after transplant, 4 which is the predominant immunoglobulin G subclass involved in the immune response to N meningitidis, 5 these patients remain at increased risk of infection with encapsulated organisms. Retrospective data suggest that the immune responses to the MCV4 vaccine are poor after HCT and that a 2-dose regimen may be required to achieve protective antibody titers 6 ; however, the immunogenicity of a single-or multiple-dose vaccine regimen has not been prospectively evaluated.…”