Immune function in children under chemotherapy for standard risk acute lymphoblastic leukaemia - a prospective study of 20 paediatric patients

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 -