Hiroshi Ayukawa

Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan

This report presents a retrospective study of 26 Japanese children with recurrent anaplastic large cell lymphoma. The first relapses were documented at a median of 10·5 months after the initial diagnosis. Twenty‐four patients achieved a second remission. After a median follow‐up period of 47 months, 18 patients are still alive: 15 patients are in second complete remission (CR), three patients are in third CR or later. The 5 year overall and relapse‐free survival rates were 61 ± 12% and 51 ± 12% respectively. The patients who received allogeneic haematopoietic stem cell transplantation during second CR showed a superior outcome to other patients.

Prognostic factors for relapsed childhood acute lymphoblastic leukemia: impact of allogeneic stem cell transplantation--a report from the Kyushu-Yamaguchi Children's Cancer Study Group.

The treatment results of childhood acute lymphoblastic leukemia (ALL) with a first relapse were retrospectively analyzed to determine prognostic factors. In particular, an attempt was made to clarify whether stem cell transplantation (SCT) had any advantages over chemotherapy.

Expression of CTLA-4 (CD152) in peripheral blood T cells of children with influenza virus infection including encephalopathy in comparison with respiratory syncytial virus infection.

Influenza virus and respiratory syncytial virus (RSV) are the most common causes of acute severe respiratory infection in children during the winter. There have been few reports about peripheral blood T cell activation in vivo in influenza virus infection and conflicting results concerning peripheral blood T cells activation in RSV infection. Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4, CD152) is a receptor present on T cells that plays a critical role in the down‐regulation of antigen‐activated immune responses. To clarify the status of peripheral blood T cells, we investigated intracellular CTLA‐4 expression in T cells in patients with influenza virus and RSV infection. We collected blood samples from 15 patients with influenza virus infection, including three with complications of influenza virus‐associated encephalopathy and 18 patients with RSV infection, as well as 44 healthy children. We determined the intracellular expression of CTLA‐4 in CD4+ and CD8+ T cells by flow cytometry. There were no significant differences in the percentages of intracellular CTLA‐4‐positive CD4+ T cells and CD8+ T cells by age. The percentages of intracellular CTLA‐4‐positive CD4+ T cells in the patients with influenza virus infection were significantly higher than those in healthy children (P < 0·01). In particular, the patients with influenza virus‐associated encephalopathy had sevenfold higher percentages of CTLA‐4‐positive CD4+ T cells than influenza patients without encephalopathy (P < 0·05). The patients with influenza virus‐associated encephalopathy had increased percentages of CTLA‐4‐positive CD8+ cells at the acute stage in comparison with the convalescent stage and in control subjects (P < 0·01, respectively). RSV patients showed no increase in CTLA‐4‐positive CD4+ T cells or CD8+ T cells. The immunological status of peripheral T cell activation is substantially different in influenza virus infection and RSV infection. The patients with RSV infection did not show any increase in CTLA‐4‐positive peripheral blood T cells. There was a remarkable increase in intracellular CTLA‐4 in CD4+ and CD8+ T cells in influenza virus‐associated encephalopathy. Down‐regulation of antigen‐activated peripheral blood T cell activation might play an important role in the pathogenesis of influenza virus‐associated encephalopathy and host defence against influenza virus infection.

Fosfomycin inhibits NF-κB activation in U-937 and Jurkat cells

Abstract Fosfomycin exerts anti-inflammatory effects through inhibiting the production of proinflammatory cytokines. Transcription of the genes for these proinflammatory cytokines is regulated by NF-κB. We tested the hypothesis that fosfomycin inhibits the activation of NF-κB induced by tumor necrosis factor-α (TNF-α) in human monocytic U-937 cells, and a T cell line (Jurkat). Western blot analysis demonstrated that fosfomycin inhibits NF-κB activation in both cells. Flow cytometry revealed that fosfomycin suppresses NF-κB activation in both cells in a dose-related manner. These findings are consistent with the idea that fosfomycin suppresses the production of proinflammatory cytokines via inhibition of NF-κB activation.

TREATMENT OF CHILDHOOD ACUTE MYELOGENOUS LEUKEMIA WITH ALLOGENEIC AND AUTOLOGOUS STEM CELL TRANSPLANTATION DURING THE FIRST REMISSION: A Report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan

A total of 64 newly diagnosed acute myelogenous leukemia patients (except FAB M3 and/or Down syndrome) under 18 years of age were consecutively enrolled into the study. Patients having an HLA-identical sibling (allo group) were assigned to undergo allogeneic bone marrow transplantation (allo BMT) in the first complete remission (CR). Others (non-allo group) were assigned to undergo autologous peripheral blood stem cell transplantation (PBSCT) or autologous BMT (auto BMT). Conditioning regimen was busulfan + melphalan for all transplantation. Of 64 patients (allo group 24; non-allo group 40), 59 (92.2%) achieved a CR. Eighteen relapses occurred (allo group 4; non-allo group 14) and 6 died during the first CR. The 5-year event-free survival (EFS) rate was 53.3 +/- 6.4% at a median follow-up period of 45 months. The 5-year EFS rates of allo and non-allo groups were 70.8 +/- 9.3% and 43.0 +/- 8.1%, respectively (p = .08). The EFS rates at 5 years post-transplant for allo BMT from an HLA-identical sibling (n = 18), PBSCT (11), and auto BMT (6) were 88.1 +/- 7.9%, 41.6 +/- 19.7%, and 83.3 +/- 15.2%, respectively. The outcome of allo BMT was superior to that of autograft. Auto BMT rather than PBSCT might contribute to a long-term survival in case of no available HLA-identical siblings.