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Immune reconstitution in children following chemotherapy for haematological malignancies: a long-term follow-up
Authors:van Tilburg Cornelis M  van Gent Rogier  Bierings Marc B  Otto Sigrid A  Sanders Elisabeth A M  Nibbelke Elisabeth E  Gaiser Jacobus F  Janssens-Korpela Pirkko L  Wolfs Tom F W  Bloem Andries C  Borghans José A M  Tesselaar Kiki
Affiliation:Department of Paediatric Haematology/Oncology, University Medical Center Utrecht, The Netherlands. c.m.vantilburg@umcutrecht.nl
Abstract:Modern intensive chemotherapy for childhood haematological malignancies has led to high cure rates, but has detrimental effects on the immune system. There is little knowledge concerning long-term recovery of the adaptive immune system. Here we studied the long-term reconstitution of the adaptive immune system in 31 children treated for haematological malignancies between July 2000 and October 2006. We performed detailed phenotypical and functional analyses of the various B and T cell subpopulations until 5 years after chemotherapy. We show that recovery of newly-developed transitional B cells and naive B and T cells occurred rapidly, within months, whereas recovery of the different memory B and T cell subpopulations was slower and incomplete, even after 5 years post-chemotherapy. The speed of B and T cell recovery was age-independent, despite a significant contribution of the thymus to T cell recovery. Plasmablast B cell levels remained above normal and immunoglobulin levels normalised within 1 week. Functional T cell responses were normal, even within the first year post-chemotherapy. This study shows that after intensive chemotherapy for haematological malignancies in children, numbers of several memory B and T cell subpopulations were decreased on the long term, while functional T cell responses were not compromised.
Keywords:Immune reconstitution  haematologic neoplasm  B‐lymphocyte subsets  T‐lymphocyte subsets  thymic output
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