1. ¹Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
2. ²Finnish Red Cross Blood Transfusion Service, Helsinki, Finland
3. ³Laboratory Diagnostics, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland

Correspondence: , Correspondence: Dr H Olkinuora, Hospital for Children and Adolescents, Helsinki University Central Hospital, PO Box 448 (Tukholmankatu 8A 5 krs.), FIN-00029 HUS, Helsinki, Finland.
E-mail: helena.olkinuora@hus.fi

⁴These authors contributed equally to this work.

Received 18 September 2006; Revised 6 November 2006; Accepted 14 November 2006; Published online 8 January 2007.

Abstract

Delayed and/or insufficient T cell recovery post hematopoietic stem cell transplantation (HSCT) leads to an increased risk of morbidity and mortality. We evaluated thymic function and its association with T cell regeneration post HSCT and identified factors involved in the process among pediatric stem cell transplant recipients. T cell regeneration in 66 pediatric patients was prospectively followed by naive T cell phenotyping, measuring of T cell receptor excision circles (TRECs) and expression of Foxp3 by regulatory T cells for the first 18 months post HSCT. TRECs were lower pre-HSCT in children with a malignant than non-malignant primary disease or immunosuppressed controls (P=0.001). Naive T lymphocyte reconstitution and thymic recovery were slow in the recipients of allogeneic stem cell grafts post HSCT. Infections caused by herpesviruses had a prognostic impact on mortality. Children with low TRECs had a high mortality (P=0.05) and low TRECs were also associated with extensive chronic graft-versus-host disease from 6 months onwards. Low amount of Foxp3 pre-HSCT was associated with an increased mortality post HSCT (P=0.03). Our study indicates an association between impaired T cell regeneration and thymic dysfunction and the clinical post transplant complications in pediatric allogeneic stem cell transplantation.