Faster Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation of Younger Children Compared with Older Children and Adults.

Allogeneic stem cell transplantation (SCT) is a potentially curative treatment of otherwise incurable malignant hematological disorders and severe immunodeficiency diseases. The post-SCT immunoincompetence can last for up to several years and might cause significant morbidity and mortality. Immune reconstitution after SCT has been studied extensively in adults, but only a few reports have been published on a paediatric population or have compared paediatric and adult population. This study was carried out in order to determine the influence of age on quantitative reconstitution of peripheral blood lymphoid subsets. A cohort of 69 adult and 109 paediatric patients received allogeneic SCT from related or unrelated fully HLA matched or 1 locus -mismatched donors for different malignant and non-malignant diseases. Analysis of lymphocyte subsets was performed at various time points: until day 30, between days 31–60, 61–90, 91–180, 181–365, between 1–2 years, between 2–5 years and more than 5 years post transplant (at the last time point only paediatric patients were analysed).

Comparing the paediatric with adult patients, we observed statistically significant faster recovery of CD19⁺, CD19⁺CD5⁺, CD4⁺CD45RA⁺ cells during the whole period of observation, and of total lymphocyte count (TLC) (< 60d and 1-2y), CD3⁺ (< 60d and 90d-2y), CD3⁺HLA-DR⁺ (31-60d), CD3⁺CD4⁺ (< 60d and > 90d), CD4⁺CD45R0⁺ (< 60d), CD3⁺CD8⁺ (< 60d and 90d - 2 y) and CD56⁺CD3⁻cells (< 31d) in the paediatric group. Interestingly, the recovery of CD56⁺CD3⁻ cells was faster from day 61-365 in the adult group (significant faster on day 91–180).

The paediatric patients were divided in two subgroups: 1) aged < 10 years; 2) aged > 10 years. The following lymphocyte subsets recovered significant faster in the younger group: TLC (31-60d, 91-365d and > 2y), CD3⁺ (91-180d and > 1y), CD3⁺HLA-DR⁺ (31-60d), CD3⁺CD4⁺ (31-60d and > day 90), CD4⁺CD45RA⁺ (61-90d and > day 180), CD4⁺CD45R0⁺ (91-180d and 2-5y), CD3⁺CD8⁺ (91-180d and > 2y), CD19⁺ (31-60d, 91-180d and 2-5y), CD19⁺CD5⁺ (31-60d, 181-365d and 2-5y) and CD56⁺CD3⁻ cells (61-180d).

The thymopoietic pathway of T helper cells is important throughout childhood; however, the thymus has a diminished capacity for the regeneration of these cells in adulthood. This can be the explanation of the faster recovery of T helper cells in the younger patients in this study. Besides, we found, that paediatric patients have a faster reconstitution of B cells and cytotoxic T cells. This might be because of the higher number of stem cells in the paediatric transplantation.