Haematologica (Feb 2011)

Thymic recovery after allogeneic hematopoietic cell transplantation with non-myeloablative conditioning is limited to patients younger than 60 years of age

  • Emilie Castermans,
  • Muriel Hannon,
  • Jacques Dutrieux,
  • Stéphanie Humblet-Baron,
  • Laurence Seidel,
  • Rémi Cheynier,
  • Evelyne Willems,
  • André Gothot,
  • Jean-François Vanbellinghen,
  • Vincent Geenen,
  • Brenda M. Sandmaier,
  • Rainer Storb,
  • Yves Beguin,
  • Frédéric Baron

DOI
https://doi.org/10.3324/haematol.2010.029702
Journal volume & issue
Vol. 96, no. 2

Abstract

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Background Long-term immune recovery in older patients given hematopoietic cell transplantation after non-myeloablative conditioning remains poorly understood. This prompted us to investigate long-term lymphocyte reconstitution and thymic function in 80 patients given allogeneic peripheral blood stem cells after non-myeloablative conditioning.Design and Methods Median age at transplant was 57 years (range 10–71). Conditioning regimen consisted of 2 Gy total body irradiation (TBI) with (n=46) or without (n=20) added fludarabine, 4 Gy TBI with fludarabine (n=6), or cyclophosphamide plus fludarabine (n=8). Stem cell sources were unmanipulated (n=56), CD8-depleted (n=19), or CD34-selected (n=5) peripheral blood stem cells. Immune recovery was assessed by signal-joint T-cell receptor excision circle quantification and flow cytometry.Results Signal-joint T-cell receptor excision circle levels increased from day 100 to one and two years after transplantation in patients under 50 years of age (n=23; P=0.02 and P=0.04, respectively), and in those aged 51–60 years (n=35; P=0.17 and P=0.06, respectively), but not in patients aged over 60 (n=22; P=0.3 and P=0.3, respectively). Similarly, CD4+CD45RA+ (naïve) T-cell counts increased from day 100 to one and two years after transplantation in patients aged 50 years and under 50 (P=0.002 and P=0.02, respectively), and in those aged 51–60 (P=0.4 and P=0.001, respectively), but less so in patients aged over 60 (P=0.3 and P=0.06, respectively). In multivariate analyses, older patient age (P