Clinical and Biological Concepts for Mastering Immune Reconstitution After Hematopoietic Cell Transplantation: Toward Practical Guidelines and Greater Harmonization

Not only the underlying mechanisms driving a long-term cure but also life-threatening side effects after hematopoietic cell transplantation (HCT) are primarily mediated by reconstitution of the immune repertoire. The composition and dynamics of reconstitution are influenced by the conditioning regimen, cell dose, graft composition, and age and type of immune suppression. However, our understanding of these mechanisms is limited due to many variations in clinical programs, including the specific type of transplantation procedure, and the absence of standardized immune monitoring after HCT. While the process of donor selection has seen significant advancements based on new biological insights, little attention has been given to optimizing cell product design in terms of numbers and composition to minimize inter-patient variability. In addition, the high inter-patient disparities in the clearance of agents used during the conditioning are rarely investigated. The lack of prospective clinical studies addressing these concepts, coupled with limited pharmaceutical company interest, fosters a consensus discussion. Our goal is to harmonize HCT interventions by exploring how individual patient differences and overall transplantation strategies impact the final effector mechanisms of HCT, specifically aiming for timely and well-balanced immune reconstitution.