Biology of Blood and Marrow Transplantation
Volume 15, Issue 4 , Pages 496-504 , April 2009

Immune Reconstitution following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation: The Impact of Expanding CD28negative CD8+ T Cells on Relapse

  • Ibrahim Yakoub-Agha

      Affiliations

    • Service des Maladies du Sang, CHU, Lille, France
    • Service d'Immunologie, CHU, Lille, France
    • EA2686, IFR114, Université Lille 2, Lille, France
    • Corresponding Author InformationCorrespondence and reprint requests: Ibrahim Yakoub-Agha, MD, PhD, Service des Maladies du Sang, UAM allogreffes de CSH, CHRU de Lille, F-59037 Lille, France.
  • ,
  • Pasquine Saule

      Affiliations

    • Service d'Immunologie, CHU, Lille, France
    • EA2686, IFR114, Université Lille 2, Lille, France
  • ,
  • Leonardo Magro

      Affiliations

    • Service des Maladies du Sang, CHU, Lille, France
  • ,
  • Pascale Cracco

      Affiliations

    • Service d'Immunologie, CHU, Lille, France
  • ,
  • Alain Duhamel

      Affiliations

    • Centre d'Etudes et de Recherche en Informatique Médicale, Université Lille 2, Lille, France
  • ,
  • Valérie Coiteux

      Affiliations

    • Service des Maladies du Sang, CHU, Lille, France
  • ,
  • Bénédicte Bruno

      Affiliations

    • Service des Maladies du Sang, CHU, Lille, France
  • ,
  • Françoise Dufossé

      Affiliations

    • Service d'Immunologie, CHU, Lille, France
  • ,
  • Jean-Pierre Jouet

      Affiliations

    • Service des Maladies du Sang, CHU, Lille, France
    • Service d'Immunologie, CHU, Lille, France
    • EA2686, IFR114, Université Lille 2, Lille, France
  • ,
  • Jean-Paul Dessaint

      Affiliations

    • Service d'Immunologie, CHU, Lille, France
    • EA2686, IFR114, Université Lille 2, Lille, France
  • ,
  • Myriam Labalette

      Affiliations

    • Service d'Immunologie, CHU, Lille, France
    • EA2686, IFR114, Université Lille 2, Lille, France

Received 31 July 2008 ,Accepted 27 November 2008.

  • Image Result

    Median absolute counts of peripheral blood CD8+ T cells (a) and their CD28-negative subset (b) by days 30, 60, 90, 180, and 365 after myeloablative HLA-matched allo-SCT, comparing patients free of any

    Median absolute counts of peripheral blood CD8+ T cells (a) and their CD28-negative subset (b) by days 30, 60, 90, 180, and 365 after myeloablative HLA-matched allo-SCT, comparing patients free of any clinical complication throughout 395 to 1564 days of follow-up (diamonds and thick solid line) with patients who experienced only cGVHD (triangles and thin solid line) and patients with relapse (squares and dashed line) exclusive of other complication. Error bars indicate the 25th to 75th percentiles. The number of patients studied who were complication-free, who had only cGVHD or only malignant relapse were 17, 13, and 14, respectively, on days 30; 18, 13, and 15 on day 60 and on day 90; 16, 13, and 10 on day 180; and 8, 10, and 8 on day 365. Positions are depicted next to each other around the time point to prevent overlaying 1 subgroup value with another. The horizontal dotted line in (a) denotes the fifth percentile of reference values for the median age of the recipients. ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001 by Kruskal Wallis test with Dunn's posttest evaluation to compare complication-free patients with those who relapsed; differences between complication-free patients and patients with only cGVHD were not significant whatever the time point.

  • Image Result
    Kaplan-Meier estimate of malignant relapse after myeloablative HLA-matched allo-SCT. The 80 patients were categorized as having absolute CD28neg CD8+ T cell numbers by day 60 postgraft falling lower (

    Kaplan-Meier estimate of malignant relapse after myeloablative HLA-matched allo-SCT. The 80 patients were categorized as having absolute CD28neg CD8+ T cell numbers by day 60 postgraft falling lower (solid line) versus equal to or higher than (dashed line) the median (179 CD28neg CD28+ T cells/mm3 of peripheral blood) determined in the subgroup of 18 patients free of any clinical complication by the time of last follow-up. The P value is for the log-rank test.

 The first 2 authors contributed equally to this work and should be considered as first authors.

 Financial disclosure: See Acknowledgments on page 503.

PII: S1083-8791(08)00588-0

doi: 10.1016/j.bbmt.2008.11.038

Biology of Blood and Marrow Transplantation
Volume 15, Issue 4 , Pages 496-504 , April 2009