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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6477-6484.
Prepublished online as a Blood First Edition Paper on March 3, 2009; DOI 10.1182/blood-2008-09-176594.


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Submitted September 2, 2008
Accepted February 14, 2009

Acute graft versus host disease transiently impairs thymic output in young patients after allogeneic hematopoietic stem cell transplantation

Emmanuel Clave*, Marc Busson, Corinne Douay, Regis Peffault de Latour, Jeannig Berrou, Claire Rabian, Maryvonnick Carmagnat, Vanderson Rocha, Dominique Charron, Gerard Socie, and Antoine Toubert

Laboratoire d'Immunologie et d'Histocompatibilite AP-HP, INSERM UMRS-940, Institut Universitaire d'Hematologie, Universite Paris-Diderot, Paris, France
Service d'Hematologie-Greffe de Moelle, Hopital Saint-Louis, AP-HP, Paris, France
INSERM U728, Institut Universitaire d'Hematologie, Paris, France

* Corresponding author; email: emmanuel.clave{at}univ-paris-diderot.fr.

Long term T-cell reconstitution after Hematopoietic Stem cell Transplantation (HSCT) is dependent on patient thymic function and affected by Graft versus Host Disease (GvHD). To assess the impact of acute GvHD (aGvHD) on thymic function, we followed a cohort of 93 patients who received HSCT from an HLA-identical sibling, mainly for hematological malignancies. Thymic output was measured by "signal-joint T-cell Receptor Excision Circles" (sjTREC) real-time PCR. Absolute sjTREC number was lower at 6 months in patients with aGvHD (p=.014), associated with lower absolute counts of naïve CD4 T-cells at 6 and 12 months (p=.04 and .02), and persistent abnormalities in T-cell repertoire diversity. Age and aGvHD affected thymic function independently in multivariate analysis. In patients less than 25 years of age, thymic function recovered almost totally at one year. As a marker of thymocyte proliferation, we quantified the {beta}TREC generated during the TCR {beta}-chain recombination, in a group of 20 age-matched patients. Mean {beta}TREC level was reduced at 6 months in patients with aGvHD, indicating an impact on early thymic differentiation rather than on intrathymic proliferation. These data show that aGvHD or its treatment, has a transient impact on thymic function in younger patients in the first months after HSCT.


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