Immune function in children under chemotherapy for standard risk acute lymphoblastic leukaemia - a prospective study of 20 paediatric patients.
Multidrug chemotherapy is a highly effective treatment for paediatric acute lymphoblastic leukaemia (ALL), but at the same time compromises immunity of patients. Immune function in a homogenous cohort of 20 children with standard- and intermediate-risk ALL was analysed by immunophenotyping, intracellular cytokine staining, assessment of serum cytokine concentrations, T-cell receptor (TCR) repertoire diversity and thymic function. B-cells were most severely affected by chemotherapy, rapidly declined under induction and did not recover until the cessation of maintenance therapy. This recovery was paralleled by a relative increase in naive IgM(+)IgD(+)CD27(-) B-cells, indicating de novo B-cell generation as the major pathway for B-cell reconstitution. T- and Natural Killer-cells were less severely affected. Although numerically diminished by chemotherapy, they had partially recovered at the end of induction. Interestingly, CD4:CD8 ratio, distribution of naive versus memory T-cells, cytokine production, TCR-repertoire complexity and thymic function were all only marginally affected by chemotherapy. Patients receiving dexamethasone had significantly less IFNgamma(+) T-cells than those receiving prednisone. Our data show that during chemotherapy in standard- and intermediate-risk paediatric ALL patients the T-cell system remains relatively well preserved. Future studies will show if this effect can be exploited for inclusion of immunotherapy in standard ALL treatment protocols.
Eyrich
Matthias
M
Department of Paediatric Haematology/Oncology and Stem Cell Transplantation, Children's Hospital, University of Würzburg, Würzburg, Germany. eyrich_m@klinik.uni-wuerzburg.de
Wiegering
Verena
V
Lim
Annick
A
Schrauder
Andre
A
Winkler
Beate
B
Schlegel
Paul G
PG
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology*; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell