Cytotoxic T lymphocytes (CTLs) undoubtedly play an important role in protection against viral infections. Virus-specific CTLs recognize virus-derived peptides in the context of major histocompatibility complex (MHC) class I molecules and lyse virus-infected cells via perforin/granzyme and Fas/Fas ligand pathways. Infection of viruses, especially herpesviruses, induces down-regulation of the surface MHC molecules, resulting in viral escape from immunosurveillance system. Viruses also modulate the chemokine/chemokine receptor system through various mechanisms, including virus-encoded chemokine ligand homologs that function as agonists or antagonists, virus-encoded cell-surface chemokine receptor homologs, virus-encoded secreted chemokine-binding proteins, and down-and up-regulation of chemokines and chemokine receptors. In this review, viral subversion of the immune system focusing on MHC expression and the chemokine system is discussed. Insight into strategies used by herpesviruses to modulate MHC expression and the chemokine system might generate novel approaches for protecting and treating viral infections.

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Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder in infancy characterized by isolated thrombocytopenia and megakaryocytopenia without physical anomalies. CAMT often progresses to bone marrow failure in later childhood, suggesting a defect in the hematopoietic stem cells as well as in the megakaryocytic lineage cells. The current studies have demonstrated that most CAMT patients suffered the disorder because of c-mpl mutation, which disrupts the function of thrombopoietin (TPO) receptor. The reported 16 types of mutations from 16 CAMT patients comprised 4 types of nonsense mutations, 4 deletions, 5 missense mutations, and 3 mutations around exon-intron junctions. Phenotype-genotype correlations were generally observed. The mutations in most patients were derived from their parents in accordance with an autosomal recessive pattern of inheritance. Many phenotypic similarities between human CAMT and murine c-mpl-deficiency were also reported. These findings confirmed the importance of TPO receptor as a development and maturation of megakaryocytic lineage and early hematopoietic progenitor cells. In the future, the analysis of the TPO receptor gene, c-mpl, in a great many patients with CAMT will help in understanding the pathophysiology of CAMT as well as its diagnosis, genetic counseling, and therapeutic judgment of the application of recombinant TPO.

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EBV-HLH is characterized by a rapidly deteriorating clinical course, caused by uncontrolled severe hypercytokinemia. In recent years, the international HLH-94 protocol has begun to be used with success in the treatment of HLH ; however, there is no consensus on the best therapy for EBV-HLH. It has been widely proven that cyclosporin-A (CSA) efficiently and rapidly suppresses T cell function and lymphokine production. It seems rational to administer CSA in the early phase of EBV-HLH to suppress the cytokine storm caused by abnormally activated T cells and activated macrophages. In this report, we present three patients with severe EBV-HLH who were treated successfully with the HLH-94 protocol-based immunochemotherapy. One was treated with the HLH-94 protocol, and two patients who suffered from very severe tissue damage were treated simultaneously with the HLH-94 protocol and CSA (3 mg/kg/day, conti.div). All of them entered remission and have been well for more than 33 months. To evaluate the clinical effects of CSA, laboratory data were compared between cases. Hematopoietic recovery and the normalization of liver enzyme and ferritin level were faster in the two patients treated with HLH-94 protocol and CSA. We observed no adverse effects attributable to CSA. These observations suggest that the introduction of CSA along with HLH-94 protocol in the early clinical course has a beneficial effect, especially on patients with severe EBV-HLH.

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We have experienced two cases of engraftment syndrome (ES) among 17 patients who underwent transplantation with autologous peripheral blood stem cells from 1994 to 2000. Four patients, including the two cases with ES, received transfusions of over 10.0×10⁶/kg of CD34 positive cells or over 10×10⁶/kg of colony forming unit-granulocyte/macrophage (CFU-GM). The other two patients without ES experienced complications of infection in the early period of peripheral blood stem cell transplantation. Prednisolone was effective to improve the symptoms of ES. To avoid ES, it is suggested that transfusion of peripheral stem cells be restricted to less than 10.0×10⁶/kg CD34 positive cells or 1.0×10⁶/kg CFU-GM.

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A 24-year-old Japanese man with a history of acute lymphoblastic leukemia, which occurred during childhood, developed malignant fibrous histiocytoma of his left knee. His past history revealed that he had undergone leukemic blast cell invasion of the left knee and subsequent radiation therapy 9 years ago. The total radiation doses for the upper part of the left tibia and the lower part of the left femur were 60 Gy and 40 Gy, respectively. Neither distant metastasis nor a relapse of leukemia occurred. A curative resection of the left femur with a noninvasive margin was performed. Adjuvant chemotherapy including high-dose methotrexate was given successfully before and after surgery ; this was followed by relapse-free survival for 3 years. The nature of postirradiation malignant fibrous histiocytoma is highly aggressive. When a patient complains of persistent symptoms in a previously irradiated field, the possibility of this tumor must be taken into account. The importance of early diagnosis cannot be over-emphasized.

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An 8-year-old Japanese girl with severe aplastic anemia who did not respond to immunosuppressive therapy underwent allogeneic bone marrow transplantation (BMT) from her HBsAg-positive HLA-identical brother. To decrease his serum HBV-DNA level, lamivudine was administered to him 7 weeks before bone marrow harvest. The pretransplant conditioning regimen consisted of cyclophosphamide and anti-thymocyte globulin, and bone marrow cells (3.38 × 10⁸ cells/kg) were then infused after plasma depletion. In order to neutralize HBV with anti-HbsAb, HB immune globulin was infused on days 0, 1 and 2. The clinical course was uneventful, and hematological recovery occurred rapidly. Her HBsAg status remained persistently negative throughout the posttransplant periods, indicating that HBV has not been transmitted to her. Lamivudine administration to the HBsAg-positive bone marrow donor may be useful to prevent HBV infection.

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We report two patients with thrombocytopenia induced by carbamazepine (CBZ). They were diagnosed as having epilepsy and treated with CBZ. Case 1, a 12-year-old girl, was admitted because of purpura on the legs and thrombocytopenia (30×10³/μl) 15 days after the initiation of CBZ treatment. Case 2, a12-year-old boy, was admitted because of purpura and thrombocytopenia (10×10³/μl) 13 days after the beginning of CBZ treatment. We studied the circulating levels of thrombopoietin (TPO) and interleukin-6 (IL-6). TPO values during the acute phase were higher than those during the recovery phase. Especially, the TPO value for Case 1 during the acute phase was higher than that in controls. IL-6 value during the acute phase was higher than that during the recovery phase for Case 2. There was no significant, fluctuation in Case 1. Further studies are required regarding the clinical relevance of TPO in drug-induced thrombocytopenia.

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