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

Abstract

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 (eg, donor-recipient 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 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.

Immune Reconstitution Following Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma at the Time of Immunotherapy

“…Our data suggest that chemotherapeutic damage either directly or indirectly to the immune system before auto-HSCT may affect immune recovery after transplantation in patients with HR-NBL. In fact, the use of serotherapy or radiotherapy before HSCT has been shown to affect post-transplantation immune reconstitution in other disease states [37,59,60]. This raises the recurrent concern of balancing chemotherapeutic tumor control with immune functionality in patients with HR-NBL.…”

Optimal approach to assessing T-cell function in haematopoietic cell transplant recipients

“…CD4 +  T cells generally take the longest to recover, and this can be delayed by GVHD and the therapies used for treatment 4. The type (related, unrelated, haploidentical etc) and source (bone marrow, peripheral blood stem cells, cord blood) of donor haematopoietic cells can affect immune reconstitution as well 5. Poor T-cell regeneration and thymic function as evaluated by TREC copies are associated with poor outcomes in the paediatric post-HCT population 4.…”

Immune reconstitution and outcomes after conditioning with anti-thymocyte-globulin in unrelated cord blood transplantation; the good, the bad, and the ugly

“…Individualized ATG dosing and TDM have the highest potential to obtain optimal ATG exposure that does not affect IR, while still preventing GvHD, in each individual patient. Although this review only focused on the effect of ATG conditioning on T-cell recovery after UCBT, more strategies to tackle delayed T-cell recovery exist (86). CB T-cells have unique properties that are currently under-utilized by conditioning with ATG.…”