The Role of Donor Age in Naive T-cell Recovery Following Allogeneic Hematopoietic Stem Cell Transplantation: The Younger the Better

Abstract

The high incidence of opportunistic infections after unrelated bone marrow transplantation has been reported. Delayed lymphocyte recovery may be associated with opportunistic infections. Immune reconstitution is influenced by recipient age and graft-vs-host disease. However, the role of donor age is largely unknown. When the effect of donor age on lymphocyte reconstitution post-transplant was examined in the murine allogeneic hematopoietic stem cell transplantation, the recovery of CD4+ naive T-cells in early post-transplant period was correlated inversely with donor age. Clinically, recipient mice transplanted from younger donors showed significantly higher survival rate and mitogenic responses than adult donors. Since CD4+ naive T-cells are mainly involved in primary immune responses to newly encountered antigens and play an important role in host defense, faster recovery of CD4+ naive T-cells in younger donors may contribute to the reduced mortality in early post-transplant period. Therefore, it is better to choose a younger donor if sufficient cell dose is available. In this review, age-related changes in hematopoiesis and lymphopoiesis as well as thymus-dependent and thymus-independent pathways following allogeneic hematopoietic stem cell transplantation are discussed.

The Different Extent of B and T Cell Immune Reconstitution after Hematopoietic Stem Cell Transplantation and Enzyme Replacement Therapies in SCID Patients with Adenosine Deaminase Deficiency

“…On the contrary, in patients receiving HSCT, the production of TRECs was stable over time (though lower than in controls) and was not different in patients who received the transplant from siblings or matched unrelated donors. Therefore, different from that previously reported in mice and humans (38,39), the extent of immune reconstitution in our patients was not correlated with the age of the donor. In addition, there was not an apparent relationship between the extent of new T cell release and the quantity of donor-engrafted T cells, because the only patient with a mixed engraftment showed a higher number of TREC + cells than that found in the other patients with total T cell engraftment.…”

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort

“…We also noted that lower CD34 cell dose had significant, though a smaller negative impact on ALC30, as have been previously reported. [40][41][42][43][44][45][46] Whether the lymphocyte content of the graft has an effect on ALC30 is not known, as those data were not available. As with previous reports, we acknowledge the lack of ALC30 subset analysis is a limitation of our study.…”

Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia

“…Actually, this speculation is supported by previous studies in mice indicating that recovery of the absolute number of lymphocytes in the early post-transplant period was delayed in recipients transplanted from older donors even after bone marrow engraftment, suggesting the delayed recovery of cytotoxic T cells and immunoglobulin-secreting B cells (leading to hypogammaglobulinemia). 26,27 Moreover, suppression of neutrophil function was shown in neutrophils from aged donors due to the decrease in secondary messenger generation, such as diacylglycerol and inositol-triphosphate, and the defect in superoxide generation which is essential for bacterial killing. 28 Unfortunately, there were no data on lymphocyte characteristics and neutrophil function in our dataset, but our epidemiological data and biological studies in mice suggest that controlling severe infection, especially bacterial infection, might be a key issue in improving prognosis following transplantation from older donors.…”