Thymic function recovery after unrelated donor cord blood or T-cell depleted HLA-haploidentical stem cell transplantation correlates with leukemia relapse

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...

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Published inFrontiers in immunology Vol. 4; p. 54
Main Authors Clave, Emmanuel, Lisini, Daniela, Douay, Corinne, Giorgiani, Giovanna, Busson, Marc, Zecca, Marco, Moretta, Francesca, Acquafredda, Gloria, Brescia, Letizia P., Locatelli, Franco, Toubert, Antoine
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 2013
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ISSN1664-3224
1664-3224
DOI10.3389/fimmu.2013.00054

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Summary: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.
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Present address: Daniela Lisini, Cell Therapy Production Unit, Foundation IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
Franco Locatelli and Antoine Toubert are co-senior authors.
This article was submitted to Frontiers in Alloimmunity and Transplantation, a specialty of Frontiers in Immunology.
Reviewed by: Laurent Garderet, Hopital Saint Antoine, France; Attilio Bondanza, S. Raffaele Scientific Institute, Italy
Edited by: Hermann Einsele, University Hospital Würzburg, Germany
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2013.00054