2 research outputs found
Thymic function recovery after unrelated donor cord blood or T-cell depleted HLA-haploidentical stem cell transplantation correlates with leukemia relapse
No full textUse 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
Association of HLA-G Low Expressor Genotype with Severe Acute Graft-versus-Host Disease after sibling Bone Marrow Transplantation
No full textBackgroundHLA-G molecules play a prominent role in immune tolerance. Structurally similar to their classical HLA homologues, they are distinct by having high rate of polymorphism in the non-coding regions including a functionally relevant 14 base pair (bp) insertion/deletion (Ins/Del) allele in the 3’ untranslated region (3’UTR), rarely examined in a hematopoietic stem cell transplantation (HSCT) setting. Here, we analyzed the potential impact of HLA-G Ins/Del dimorphism on the incidence of acute graft versus host disease (aGvHD), transplant related mortality (TRM), overall survival (OS) and incidence of relapse after HSCT using bone marrow as stem cell source from HLA matched donors. MethodsOne hundred and fifty seven sibling pairs, who had undergone HSCT, were studied for the distribution of the HLA-G 14bp Ins/Del polymorphism using a polymerase chain-reaction (PCR)-based technique. Potential genetic association with the incidence of aGvHD, TRM and OS was analyzed by uni- and multivariate analyses. ResultsUnivariate analysis showed that the homozygous state for the 14 bp Ins allele is a risk factor for severe aGvHD (grade III and IV) (P = 0.008), confirmed subsequently by multivariate analysis (hazard ratio HR = 3.5; 95% confidence interval 95%CI = 1.3-9.5; P = 0.012). We did not find any association between HLA-G polymorphism and the other studied complications. ConclusionsOur data suggest that the HLA-G low expressor 14bp Ins allele constitutes a risk factor for the incidence of severe aGvHD in patients who received bone marrow as stem cell source
