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Blood, 15 July 2006, Vol. 108, No. 2, pp. 763-769.
Prepublished online as a Blood First Edition Paper on March 30, 2006; DOI 10.1182/blood-2006-01-009241.
 Previous Article | Next Article 
Submitted January 19, 2006
Accepted March 10, 2006
Early determinants of long-term T-cell reconstitution
after hematopoietic stem cell transplantation for severe
combined immunodeficiency
Jose A Borghans, Robbert G Bredius, Mette D Hazenberg, Helene Roelofs, Els C Jol-van der Zijde, Jeroen Heidt, Sigrid A Otto, Taco W Kuijpers, Willem E Fibbe, Jaak M Vossen, Frank Miedema, and Maarten J van Tol*
Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands
* Corresponding author; email: m.j.d.van_tol{at}lumc.nl.
The immune system of patients with severe combined
immunodeficiency (SCID) reconstitutes to a large extent
during the first years post-hematopoietic stem-cell
transplantation (HSCT). It was suggested, however, that
accelerated loss of thymus output may cause impaired
immune function at the long term. To address this issue,
we studied SCID patients who underwent allogeneic HSCT 5
to 32 years earlier, and identified early determinants
of long-term T-cell reconstitution. A variety of immune
parameters were analyzed both early (1-4 years) and late
(5-32 years) after HSCT. Late after HSCT, a clear
distinction could be made between a group of 8 patients
with impaired T-cell reconstitution and 11 patients with
good immune reconstitution. Importantly, in patients
with decreased long-term T-cell reconstitution, T-cell
recovery was already poor early after HSCT,
demonstrating that long-term immune failure was not
caused by accelerated loss of thymus output or long-term
graft failure, but resulted from poor early grafting.
The number of T-cell receptor excision circles (TRECs)
early after HSCT was most predictive for long-term T-
cell reconstitution. Frequent monitoring of T-cell
immunity and TREC numbers early after HSCT may thus
serve to timely identify patients who will fail to
reconstitute properly and who may need additional
treatment.
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