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-nearfuture clinically relevant strategies before, during, and after transplantation to achieve successful T-cell IR. Potent strategies are choosing the right HCT source (eg, donorrecipient matching, cell dose, graft manipulation), individualized conditioning and serotherapy (eg, antithymocyte 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 are important as well because this complication and the subsequent need for immunosuppression affects T-cell IR and function. These options aim for personalized precision transplantation, where alloHCT therapy is designed to boost a wellbalanced T-cell IR and limit complications in individual patients, resulting in overall lower morbidity and higher survival chances.