Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group

• OBJECTIVE: The aim was to examine the immune reconstitution after current chemotherapy for childhood ALL, with a special focus on finding immunologic variables that predict a poor immune response to vaccinations. PROCEDURE: In a cross-sectional study of 31 children after treatment with the NOPHO ALL-1992 protocol peripheral blood lymphocyte subsets, T- and B-cell function in vitro and serum immunoglobulins (Ig) were measured. All patients were examined once, at 1 or at 6 months after cessation of chemotherapy, immediately before vaccination with DT and Hib. RESULTS: Lymphocytes, T-cells, and CD4+ T-cells were low at 6 months after treatment. Naive T-cell subsets were more reduced than memory subsets. In the high risk (HR) ALL group, CD8+ T-cells were reduced at 6 months. NK-cells were low at 1 month, but normal at 6 months; however, the CD3+CD56+ (NKT) subset was reduced at both time points. Total B-cell number was low at 1 month, but normal at 6 months. A relative increase of CD5+ B-cells (B-1 cells) was evident, particularly in the HR group. Antigen-independent T- and B-cell function in vitro were affected at 1 month, but virtually normalized at 6 months. Serum IgM level was decreased at 1 month and IgG3 level was increased at 1 and 6 months. CONCLUSIONS: This study shows that immune reconstitution after childhood ALL is slower than previously reported and emphasizes the influence of treatment intensity. The most intensively treated patients still have persistent abnormalities in T-, B-, and NK-cell subsets at 6 months post therapy and show a poor response to immunization with T-cell dependent antigens. In the HR group, routine re-immunizations before this time point are of limited benefit, and the effect of repeated vaccinations should be evaluated.

Nyckelord

Adolescent

Adult

Antigens

CD/analysis

Antineoplastic Agents/adverse effects/therapeutic use

B-Lymphocytes/cytology/immunology

Case-Control Studies

Child

Child

Preschool

Cross-Sectional Studies

Humans

Immune System/cytology/*physiology

Immunoglobulins/blood

Immunosuppression/methods

Killer Cells

Natural/cytology/immunology

Leukemia

Lymphocytic

Acute

L1/*drug therapy

Lymphocyte Subsets/cytology

*Regeneration

T-Lymphocytes/cytology/immunology

Time Factors

*Vaccination

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