Strategies before, during, and after hematopoietic cell transplantation to improve T-cell immune-reconstitution

T-cell immune reconstitution (IR) after allogeneic hematopoietic cell transplantation (allo-HCT) is highly variable between patients and may take several months to even years. Patients with delayed or unbalanced T-cell IR have a higher probability of developing transplantation-related-morbidity, -mortality, and relapse of disease. Hence, there is a need for strategies to better predict and improve IR to reduce these limitations of allo-HCT. In this review, we provide an update of current and in near-future clinically relevant strategies before, during, and after transplantation to achieve successful T-cell IR. Potent strategies are choosing the right HCT-source (e.g. donor-recipient matching, cell-dose, graft manipulation), individualized conditioning and serotherapy (e.g. Anti-Thymocyte-Globulin), nutritional status, exercise, home care, modulation of microbiota, enhancing homeostatic peripheral expansion, promoting thymopoiesis, and the use of adjuvant targeted cellular immunotherapies. Strategies to prevent Graft-versus-Host-Disease (GvHD) are important as well, for this complication and subsequent need for immunosuppression affects T-cell IR and function. These options aim for personalized precision-transplantation, where allo-HCT therapy is designed to boost a well-balanced T-cell IR and limit complications in individual patients, resulting in overall lower morbidity and higher survival chances.