Immune function in children under chemotherapy for standard risk acute lymphoblastic leukaemia - a prospective study of 20 paediatric patients
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Immune function in children under chemotherapy for standard risk acute lymphoblastic leukaemia - a prospective study of 20 paediatric patients. / Eyrich, Matthias; Wiegering, Verena; Lim, Annick; Schrauder, Andre; Winkler, Beate; Schlegel, Paul G.
in: BRIT J HAEMATOL, Jahrgang 147, Nr. 3, 11.2009, S. 360-370.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Immune function in children under chemotherapy for standard risk acute lymphoblastic leukaemia - a prospective study of 20 paediatric patients
AU - Eyrich, Matthias
AU - Wiegering, Verena
AU - Lim, Annick
AU - Schrauder, Andre
AU - Winkler, Beate
AU - Schlegel, Paul G
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - Adolescent
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - B-Lymphocyte Subsets/drug effects
KW - Child
KW - Child, Preschool
KW - Cytokines/biosynthesis
KW - Female
KW - Genetic Variation
KW - Humans
KW - Immunity, Cellular/drug effects
KW - Immunophenotyping
KW - Killer Cells, Natural/drug effects
KW - Lymphocyte Count
KW - Male
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
KW - Prospective Studies
KW - Receptors, Antigen, T-Cell/genetics
KW - T-Lymphocyte Subsets/drug effects
KW - Thymus Gland/immunology
U2 - 10.1111/j.1365-2141.2009.07862.x
DO - 10.1111/j.1365-2141.2009.07862.x
M3 - SCORING: Journal article
C2 - 19694715
VL - 147
SP - 360
EP - 370
JO - BRIT J HAEMATOL
JF - BRIT J HAEMATOL
SN - 0007-1048
IS - 3
ER -