Abstract
Use of alternative donors/sources of hematopoietic stem cells (HSC), such as cord blood (CB) or HLA-haploidentical (Haplo)-related donors, is associated with a significant delay in immune reconstitution after transplantation. Long-term T-cell immune reconstitution largely relies on the generation of new T cells in the recipient thymus, which can be evaluated through signal joint (sj) and beta T-cell-Receptor Excision Circles (TREC) quantification. We studied two groups of 33 and 24 children receiving, respectively, HSC Transplantation (HSCT) from an HLA-haploidentical family donor or an unrelated CB donor, for both malignant (46) and non-malignant disorders (11). Relative and absolute sj and beta-TREC values indicated comparable thymic function reconstitution at 3 and 6 months after the allograft in both groups. Compared to children with non-malignant disorders, those with hematological malignancies had significantly lower pre-transplantation TREC counts. Patients who relapsed after HSCT had a significantly less efficient thymic function both before and 6 months after HSCT with especially low beta-TREC values, this finding suggesting an impact of early intra-thymic T-cell differentiation on the occurrence of leukemia relapse.
Highlights
Whenever an HLA-identical related donor is not available, alternative sources of donors/stem cells are to be used for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (Beatty et al, 1995)
At month 6, only CD4+ cells remained significantly lower (p = 0.022) in the former group. These results confirm the detrimental role of T-cell depletion (TCD) of the graft on early reconstitution of mature T cells and the role played by homeostatic expansion of T cells transferred with the graft in the case of unrelated donor CB transplantation (UCBT) (Roux et al, 1996)
At 6 months, there was a great inter-patient variability, the median number of Signal-joint T-cell-Receptor (TCR) Excision Circles (sjTREC) numbers almost returned to pre-graft levels with 281 (0–31,286) and 647 (0–16,395) sjTREC/150,000 Peripheral Blood Mononuclear Cells (PBMC), for Haplo-HSCT and UCBT patients (Figure 1A), respectively
Summary
Whenever an HLA-identical related donor is not available, alternative sources of donors/stem cells are to be used for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (Beatty et al, 1995) Both unrelated Cord Blood (CB) and HLA-haploidentical (Haplo) family donors provide an effective treatment for many malignant and non-malignant diseases in children (Rocha and Locatelli, 2008). Despite improvement in the graft procedure such as use of T-cell depletion (TCD) and infusion of high doses of CD34+ cells, which allows engraftment and reduces graft-versus-host disease (GvHD) in Haplo-HSCT recipients (Aversa et al, 1994; Handgretinger et al, 2001), a significant delay in immune reconstitution still remains a relevant problem, leading to a high incidence of both opportunistic infection and, in the absence of NK alloreactivity, to relapse (Ball et al, 2005; Wils et al, 2011). We showed recently, in 33 Haplo-HSCT patients an association between low thymic function and an increased risk of leukemia relapse (Clave et al, 2012)
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