title: Cellular immunosuppression in children with acute lymphoblastic leukemia: effect of consolidation chemotherapy.
abstract: The present study was designed to evaluate the chemotherapy-induced cellular immunosuppression in 20 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy. Peripheral blood was serially obtained from leukemic children during vincristine/cyclophosphamide/6-mercaptopurine/prednisone combined consolidation chemotherapy. The mean absolute number of peripheral blood lymphocytes as well as the mean absolute numbers of lymphocyte subsets (T cells, T cell subsets, B cells, and natural killer cells) from leukemic children before consolidation chemotherapy were all significantly lower than in control subjects; however, the percentages of lymphocyte subsets were similar in both groups. After consolidation chemotherapy, the percentages of CD4+ T lymphocytes and natural killer (NK) cells were significantly decreased and the percentages of monocytes and CD8+ T lymphocytes were significantly increased. Phytohemagglutinin- and 12-O-tetradecanoylphorbol-13-acetate-induced production of interleukin-2 (IL-2) and NK-cell-mediated cytotoxic activity by peripheral blood mononuclear cells (PBMC) were also substantially decreased in the post-therapy groups. NK activity correlated with the percentage of NK cells in PBMC. In contrast, OK432-induced production of tumor necrosis factor alpha (TNF alpha) and killer activity against NK-resistant target cells were significantly increased after therapy as compared with the pre-therapy and control groups. TNF alpha production correlated with the percentage of monocytes in PBMC. These results demonstrate that substantial quantitative and qualitative chemotherapy-induced abnormalities of the cellular immune system are present in the majority of patients treated with ALL. It is also suggested that the increased TNF alpha production by monocytes and the appearance of potent killing activity against NK-resistant targets might compensate for the defects of IL-2 production and NK activity during intensive consolidation chemotherapy.
authors.affiliation: Department of Pediatrics, Mie University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Komada
authors.forename: S L
authors.initials: SL
authors.lastname: Zhang
authors.forename: Y W
authors.initials: YW
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Hanada
authors.forename: T
authors.initials: T
authors.lastname: Shibata
authors.forename: E
authors.initials: E
authors.lastname: Azuma
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015122:Mercaptopurine / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010844:Picibanil / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D011241:Prednisone / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil; D014750:Vincristine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D011241:Prednisone