Clinical findings and immunological abnormalities in patients with chronic active Epstein-Barr (EB) virus infection (CAEBV) were reviewed. The most common symptoms of this disease consist of prolonged fever and lymphoproliferative syndrome. EB-virus specific and nonspecific cellular immunities have been reported to be defective, and these defective immune functions might be corresponding to the development of CAEBV. T/ NK cells are mainly infected with EB-virus, and clonal proliferation of these cell lineages was frequently observed in CAEBV. Several immune abnormalities were also observed in parents of the patients, and NK cell activity of the patients and their mothers were well correlated. Curiously, clinical signs and immunological abnormalities similar to CAEBV were observed in some patients with autoimmune lymphoproliferative syndrome (ALPS). Although CAEBV is a critical disease with poor prognosis, diagnostic criterion and the methods for treatment have not been established. Bone marrow transplantation and adoptive immunotherapy with EB-virus specific cytotoxic T lymphocytes are considered effective in some patients.

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L-Asparaginase (ASP) is a useful antileukemic agent, but has been believed to be very toxic. Common toxic reactions are associated with hypersensitivity and inhibition of hepatic protein synthesis. Under the current method of administration, most toxic reactions are tolerable and avoidable. However, we must be alert to rare serious complications such as anaphylaxy shock, acute pancreatitis, and thrombotic complication of the central nervous system. For prophylaxis and early diagnosis, very close observation of the clinical symptoms are necessary during or after the treatment with ASP. Laboratory tests such as plasma antithrombin III and serum amylase may be useful for monitoring those complications.

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Nine of severe aplastic anemia (SAA) patients who lacked an identical HLA donor for a marrow transplant underwent testing of various therapeutic modalities. Actuarial survivals of these patients at 3 and 5 years were 100% and 87.5%, respectively. Response rates were greater in patients treated with antithymocyte globulin (ATG) /antilymphocyte globulin (ALG) plus methylprednisolone (mPSL). The long-term administration of the granulocyte colony-stimulating factor (G-CSF) induced a multilineage hematological recovery in 3 of 4 patients, and a dose-dependent increase/decrease in the neutrophilic and platelet counts was observed in 2. A patient who underwent lymphocytapheresis 14 years ago remains in hematological remission without need of further therapy. The prognoses have been good for patients with subnormal to normal bone marrow CFU-C and for patients with an early increase of CFU-Cs after immunosuppressive therapy. Three patients with CFU-C-suppressing T lymphocytes have exhibited a good response to ATG/ALG therapy. Long-term bone marrow cultures (LTBMCs) revealed an impaired CFU-C generation; however, the prognoses of 2 patients in whom CFU-C production was maintained for 8 weeks remain good. Although ATG/ALG were found to be effective therapies for patients with SAA, the HD _γgl and G-CSF therapies are also beneficial. Lymphocytapheresis might be one of the useful therapeutic modalities for SAA patients. A bone marrow CFU-C assay and an LTBMC may be useful for selecting the proper treatment regimen for SAA patients.

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A novel pre-B leukemic cell line carrying TEL/AML1 chimeric mRNA, KOPN-41, established from the bone marrow blood at initial diagnosis, was characterized. KOPN-41 cells expressed surface CD10, CD19, CD20, CD22, and HLA-DR antigens and had cytoplasmic μ-chain, compatible with the definition of pre-B characteristics. A normal karyotype was obtained by conventional chromosome analysis, but a reverse transcriptase-polymerase chain reaction method finally confirmed TEL/AML1 chimeric mRNA. Besides to the reciprocal translocation between the 12 th and 21st chromosomes, the fluorescence in situ hybridization method demonstrated the deletion of another allele of the TEL gene and a duplication of the translocated AML1 gene.

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Since the 1960s, intrathecal therapy with or without cranial irradiation in combination with systemic chemotherapy has greatly contributed to reduce the incidence of central nervous system (CNS) recurrence in acute lymphoblastic leukemia (ALL) in children. However, CNS recurrence has continued to be still observed in approximately 5-10% of patients. We report 4 children with an isolated CNSrelapse of ALL, diagnosed from 1986 to 1993. All except one were initially treated with standard risk regimen, including high-dose methotrexate (MTX) infusion and intrathecal medication without cranial irradiation. Thelength of first remission ranged from 24 to 56 months. All patients achieved second remission by triple-drug intrathecal medication combined with high-risk ALL-oriented systemic chemotherapy followed by radiation therapy. Second, a CNS relapse occurred in two cases 17 and 84 months later, respectively. To one of them, melphalan and total body irradiation with purged marrow rescue was carried. As a result, all 4 patients are alive in complete remission.

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We report two patients with severe aplastic anemia who rechallenged with antiserum from the same animal source. One patient received a second course of antiserum therapy because cyclosporine A could not be tapered, and the other did because of rapidly progressing anemia. Both patients rechallenged with equine ATG or ALG, and hematological improvement was observed without serious complications. We suggest that repeated courses of ATG or ALG for severe aplastic anemia are useful if careful prophylactic measures against anaphylactic reactions are employed.

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A 10-year old boy was admitted to our hospital with generalized lymphoadenopathy. He had a mediastinal mass, but no organomegaly. Based on a right cervical lymph-node biopsy, he was diagnosed as having lymphoblastic-type non-Hodgkin's lymphoma (NHL). An immunological study of tumor cells showed only positive surface Ia and CD7 antigens. When the patient relapsed in the right inguinal lymph nodes, the tumor cells were positive for CD5, CD 10, and CD13. The blasts in the bone marrow 34 months after diagnosis showed additional positivity for CD1 lb, CD33, and CD34. A cytochemical study revealed positivity for peroxidase and Sudan-Black B staining. When we examined the gene rearrangement of the tumor cells at diagnosis, at relapse, and at myeloid conversion, they all showed the same T-cell receptor 6 gene rearrangement and germ line of the other genes. As a result, the monoclonality of tumor cells was confirmed. We therefore suspected that the NHL of this case originated from an immature prothymocyte (CD7 +) and thereafter developed into more differentiated lymphoid and/or myeloid precursor cells with the progression of disease and treatment.

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We report on a girl with juvenile chronic myelogenous leukemia (JCML), who presented at the age of two months with hepatosplenomegaly and leukocytosis. At seven months, she underwent allogeneic bone marrow transplantation (BMT) from her completely HLA-matched brother, when the spleen was enlarged to pelvic cavity, and anemia and thrombocytopenia developed profoundly. Splenectomy was not done before BMT despite remarkable splenomegaly and hypersplenism. She was conditioned with busulfan 5 mg/kg/day × 4 days (days-8, -7, -6, -5), etoposide 60 mg/kg/day × 1 day (day-4), and cyclophosphamide 60 mg/kg/day × 2 days (days-3, -2), and prophylaxis for GVHD consisted only of methotrexate. Although engraftment was confirmed with chromosomal analysis on day 21, frequent transfusions of both erythrocytes and thrombocytes had been needed for several weeks. After cessation of prophylaxis for GVHD, acute GVHD (Grade 3) of skin and liver appeared at about day 60, thereafter splenomegaly started to reduce, and anemia and thrombocytopenia improved gradually. An improvement of acute GVHD was induced by steroid pulse therapy (methylprednisolone 50 mg/kg/day X 3 days and tapered). Six months after BMT, chronic GVHD (dry skin, decrease of lacrymation, photophobia) was observed. She has been in complete remission for 10 months. We suggest that in JCML, splenectomy is not necessary except when the condition is critical.

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We report two children with primary mediastinal large B cell lymphoma (PMLCL). Patient 1, a 10-year-old girl, presented with engorged veins on the chest and abdominal wall. MR image revealed a large mediastinal mass that invaded and occluded the superior vena cava. Patient 2, a 14-year-old boy, presented with swallowing discomfort and dry cough. Imaging study showed a huge mediastinal mass and pleural effusions. In both patients, the tumor cells showed mature B cell phenotype, and histopathology in patient 2 showed diffuse large-cell lymphoma with sclerosis. We treated them with an intensive short-term chemotherapy regimen “B-93 protocol.” Both patients showed good response initially, but residual tumors were observed after the completion of chemotherapy. We confirmed complete remission by open biopsy in patient 1 and imaging study in patient 2. These two cases suggest that residual tumors of PMLCL are due to sclerosis and that they do not always show a resistance to treatment.

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We reported three young girls with localized Langerhans cell histiocytosis of ilium, who were accompanied by gait disturbance. Plain radiograph showed the lytic defect of ilium, and computed tomography scans revealed mass lesion with bone destruction. They were diagnosed as eosinophilic granuloma by open biopsy. Their clinical courses followed the treatment well with direct injection of steroids into bone lesion. In Patient 3 with rib lesion other than iliac lesion at presentation, the osteolytic lesion of both rib and ileum disappeared within 2 months after only a single injection of methylprednisolone into the ilium. This suggested that the direct-injection therapy of steroids may be effective in cases with multiple bone lesions. Because the direct injection of steroids is relatively noninvasive and easy without severe complications, it might be considered as a first-line therapy for the localized Langerhans cell histiocytosis of bone.

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