ABSTRACT
Chemotherapy for childhood acute lymphoblastic leukemia may cause severe immune damage. The lymphocyte compartment of 140 patients during and after a new strongly reduced (standard risk (SR), n=43) and intensive chemotherapy regimen (medium risk (MR), n=97) was studied between 2006 and 2009. Transitional and naive B cells and IgG(+)/A(+), IgM(+) and IgM only memory B cells were significantly reduced during chemotherapy; significantly more in MR group. One year after treatment CD27(+)IgG(+)/A(+), IgM(+) and IgM only memory B cells had still not fully recovered, but this was not confined to the MR group. The T cell compartment was less but also significantly affected during chemotherapy and recovered to normal levels. In the MR group, NK cells had not fully recovered to normal levels 1 year after treatment. Thus, intensive chemotherapy regimens cause severe, mainly B cell memory damage that persists even 1 year after treatment.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Adolescent , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Child , Child, Preschool , Female , Flow Cytometry , Humans , Immunologic Memory/drug effects , Immunologic Memory/immunology , Infant , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Lymphocyte Count , Lymphocytes/drug effects , Lymphocytes/immunology , Male , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Time Factors , Treatment Outcome , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunologyABSTRACT
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.
