T cell regeneration in pediatric allogeneic stem cell transplantation.
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.
Olkinuora
H
H
Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. helena.olkinuora@hus.fi
Talvensaari
K
K
Kaartinen
T
T
Siitonen
S
S
Saarinen-Pihkala
U
U
Partanen
J
J
Vettenranta
K
K
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D051799:Delayed Graft Function; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D007239:Infections; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012038:Regeneration; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology; D014184:Transplantation, Homologous
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011948:Receptors, Antigen, T-Cell