4.5 Review

Immune Reconstitution After Allogeneic Haematopoietic Cell Transplantation: From Observational Studies to Targeted Interventions

Journal

FRONTIERS IN PEDIATRICS
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fped.2021.786017

Keywords

immune reconstitution; thymic function; peripheral expansion; T-cell receptor repertoire diversity; graft-vs; -host disease; -leukaemia effect; infectious complications

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Immune reconstitution after allogeneic hematopoietic cell transplantation is crucial for transplant outcomes. Younger children experience faster immune cell recovery, leading to lower rates of graft vs. host disease and complications. Strategies to influence immune reconstitution are still evolving. Recovery of antigen-specific immune cells plays a significant role in protecting against viral diseases, while the association between immune reconstitution and graft vs. leukemia effect is less understood. Future improvements in immune reconstitution may impact transplant procedures.
Immune reconstitution (IR) after allogeneic haematopoietic cell transplantation (HCT) represents a central determinant of the clinical post-transplant course, since the majority of transplant-related outcome parameters such as graft-vs.-host disease (GvHD), infectious complications, and relapse are related to the velocity, quantity and quality of immune cell recovery. Younger age at transplant has been identified as the most important positive prognostic factor for favourable IR post-transplant and, indeed, accelerated immune cell recovery in children is most likely the pivotal contributing factor to lower incidences of GvHD and infectious complications in paediatric allogeneic HCT. Although our knowledge about the mechanisms of IR has significantly increased over the recent years, strategies to influence IR are just evolving. In this review, we will discuss different patterns of IR during various time points post-transplant and their impact on outcome. Besides IR patterns and cellular phenotypes, recovery of antigen-specific immune cells, for example virus-specific T cells, has recently gained increasing interest, as certain threshold levels of antigen-specific T cells seem to confer protection against severe viral disease courses. In contrast, the association between IR and a possible graft-vs. leukaemia effect is less well-understood. Finally, we will present current concepts of how to improve IR and how this could change transplant procedures in the near future.

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