Recent topics regarding childhood non-Hodgkin's lymphoma (NHL) are reviewed. First is a new classification system of malignant lymphoma proposed by the International Lymphoma Study Group : Revised European-American Lymphoma (REAL) classification, which incorporates recent knowledge about the morphological, immunophenotypic and genetic information of different lymphomas. In contrast to various types of lymphomas in adults, childhood NHL is primarily limited to three histologic types (lymphoblastic-LBL, small noncleaved-SNC and diffuse large-cell DLC). Therefore, the clinical utility of the REAL classification for childhood NHL must await the accumulation of our experiences. The second topic is the current knowledge on molecular abnormality in NHL. The recent developments in molecular assays have identified various genetic abnormalities which underlie the three histologic types of childhood NHL. The door has been opened to understand the precise link between molecular alterations and the clinical behavior of each subtype of NHL. Thirdly, significant progress in the treatment of NHL is reviewed. A dramatic improvement in the cure rate of children with SNC has been obtained since 1985. More specific approaches with shortened and more doseintensive use of cyclophosphamide, methotrexate and intensive intrathecal therapy have produced event-free survival rates of 70-80% for stage III/IV SNC. Finally, the development of second leukemia (acute myeloid leukemia) among children with NHL is discussed. Although the exact pathogenesis is unknown, accumulated data suggests the use of etoposide on a certain schedule (twice weekly) is the most important risk factor.

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To determine whether or not recent advances in therapy, except for the use of bone marrow transplantation (BMT), contribute to improve the prognosis of aplastic anemia, we retrospectively investigated the survival rate, remission rate and prognostic factors of 33 children with aplastic anemia hospitalized in the Pediatric Department of Hirosaki University School of Medicine. The study covers 3 decades, from 1965 to 1994, and cases were divided to 3 groups according to the chronological period of onset (group I, 1965-1974 ; group II, 1975-1984 ; group III, 1985-1994). For the average of all cases, the survival rate was 69.7% and remission rate was 51.5%. The survival rate was obviously increased in the cases of severe aplastic anemia in group III as compared to group I and group II. However, the remission rate for severe aplastic anemia did not change, rather the remission rate decreased in mild and moderate cases with each passing decade. These results indicate that recent treatments excluding BMT, including immunotherapy and cytokine administration, are not always so favorable as therapies for aplastic anemia. The highest mortality rate was found in the age group under 3 years; so an important prognostic factor was considered to be the disease severity and the age at onset.

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In order to determine the prognostic factor of aplastic anemia (AA) patients, we examined the number of bone marrow colony-forming units-erythroid (CFU-E), serum erythropoietin (Epo), interleukin-2 (IL-2) production and interferon-γ (IFN-γ) production in AA patients. 1. The number of CFU-E colonies was lower in patients with severe AA than in patients with mild or moderate AA. The recovery of CFU-E colonies under treatment was a favorable sign in the course of illness. 2. The serum Epo level depended more on the condition of the patients at the time of examination than the severity at onset. 3. Serum IL-2 production increased in transfusion dependent cases. 4. Serum IFN-y production did not decrease in the cases of AA patients as compared to the controls.

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We evaluated the efficacy of a single administration of half the dose of intravenous immunoglobulin (IVIg) recommended in current therapy to reduce bleeding tendencies and increase platelet counts. Nine cases with idiopathic thrombocytopenic purpura were treated one time with IVIg (1.0 g/kg). Platelet counts before treatment were 0.97 ± 0.6×10⁴/μl. After IVIg treatment, the bleeding tendency improved in all cases, andplatelet counts on the following day were 4.6 ± 2.6×10⁴/μl. Platelet counts increased to more than 5.0×10⁴/μl over an average of 2.2 days, and in 7 out of 9 cases, platelet counts increased by this amount in less than 2 days. Subsequently, 3 cases maintained normal platelet counts without further therapy, while in the other cases, theplatelet count remained at more than 5.0×10⁴/μl for 2 to 17 days. No side effects appeared in any of the cases.We conclude that a single-administration IVIg therapy (1.0 g/kg) seems as effective as the currently recommended therapy in promoting an early increase in platelet counts and in reducing bleeding tendencies. However, a controlled study using a larger number of cases must be carried out.

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The Bone Marrow Transplantation Committee of the Society has conducted anannual registry of bone marrow transplantation in children in Japan since 1983. As of June 30, 1996, 3, 221patients had received stem-cell transplantation, an increase of 535 patients from the 1995 registry, andwere registered from 125 institutions. In this paper, the results of the main diseases were analyzed to determine whether or not the actuarial disease-free survival (DFS) rates of allogeneic bone marrow transplantation were different before and after 7/1/1990 in addition to annual analysis. There were no significant differences in the patients with acute lymphoblastic leukemia or acute myeloid leukemia who received HLA-matched sibling bone marrow at the 1st complete remission (CR) or 2nd CR between the two periods. The DFS rate of patients transplanted at the 3rd CR after 7/1/1990 was better than that of patients transplanted before 7/1/1990 (45.6 ± 14.1% vs 14.3 ± 13.0%, p < 0.01). There were no significant differences in adult-type chronic myelocytic leukemia patients who received HLA-matched sibling bone marrow at the 1st chronic phase, although there was a tendency of better results for patients who were preconditioned with total body irradiation regimens in both of the periods. The DFS rates of patients with severe aplastic anemia who received HLA-matched sibling bone marrow (110 cases) or unrelated bone marrow (19 cases) after 7/1/1990 were 89.2 ± 6.2% and 68.4+ 20.9%, respectively. Unrelated bone marrow transplantation from “donor bank” donors was performed on 214 children with an overall DFS rate of 49.2 8.6%. Allogeneic cord blood stem-cell transplantation was done on 8 children, and allogeneic PBSCT was performed on 27 children.

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A case of early onset hemorrhagic cystitis after an allogeneic bone marrow transplantation successfully treated with prostaglandin E₁bladder instillations is reported. The patient, a five-year-old boy who suffered from non-A non-B non-C hepatitis at four years of age, was rehospitalized because of anemia and thrombocytopenia, and diagnosed as having post-hepatitis aplastic anemia. After a bone marrow transplantation from a HLA identical sibling, hemorrhagic cystitis developed on day one. Bladder instillations with prostaglandin E₁ (500 μg/body) were started on day 23 because treatment with 10% Maalox^® (aluminum hydroxide gel and magnesiumhydroxide, Yamanouchi Co., Tokyo, Japan) from day 3 was not effective. The microscopic hematuria disappeared dramatically on day 29. There were no severe side effects of bladder instillations with prostaglandin E₁observed. Therefore, this treatment may be promising for the treatment of severe hemorrhagic cystitis because ofits availability without any severe systemic side effects.

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Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiencysyndrome, and is characterized by a triad of thrombocytopenia with small platelet size, recurrent infection and eczema. Its novel gene was identified in 1994. At present, stem cell transplantation (SCT) is the only established therapy, and this is performed in the early stage if a HLA-matched donor is available. We report on a 19-year-old WAS patient who received a transplantation from an unrelated donor BMT (UD-BMT). He was the oldest WAS patient to undergo SCT in Japan. Inspite of severe complications, his SCT was successfully conducted. The usefulness of UD-BMT for WAS patients is discussed.

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We report a case of an 8-year-old boy with relapsed acute lymphocytic leukemia who was complicated with adult respiratory distress syndrome (ARDS) due to Streptococcus mitis after bone marrow transplantation (BMT). Although he underwent allogeneic BMT during his third complete remission in November 1991, bone marrow relapse developed in April 1992. During the fourth reinduction therapy, severe dyspnea and hypotension developed and S. mitis was identified by a venous blood culture. A chest X-ray confirmed the diagnosis of ARDS. Cultured S. mitis was susceptible to the antibiotics administered at that time, and the ARDS was successfully treated by mechanical ventilation with PEEP of 8 cmH₂O and steroid pulse therapy. However, the patient died of multiple organ failure with a systemic fungal infection two weeks after recovery from ARDS. Septicemia and ARDS due to α-Streptococci are increasing among pediatric patients with malignant diseases. This case indicates the importance of the awareness of septicemia and ARDS due to α-Streptococci during intensive chemotherapy against malignant pediatric diseases.

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A 5-year-old girl with acute lymphoblastic leukemia showed increased uptake in the bone and decreased uptake in the liver by⁶⁷Ga scintigraphy. Subsequently, the bone uptake decreased after beginning remission induction treatment. It is believed that⁶⁷Ga-citrate was taken by the leukemic cells through the transferrin receptors and distributed to the systemic bone marrow.⁶⁷Ga scintigraphy is widely used for malignancies such as malignant lymphoma, however, its significance for leukemia has not been evaluated.⁶⁷Ga scintigraphy may be useful to evaluate the extent of bone marrow invasion of leukemic cells and response to treatment.

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Cord blood stem cell transplantation (CBSCT) was performed on a patient with advanced neuroblastoma. The patient was a girl, 1 year and 6 months old, who had shown partial remission following treatment with intensive chemotherapy according to the new A 1 regimen. However, 3 weeks after surgical removal of the original tumor and metastatic lymph nodes in the abdomen, extensive relapse occurred. The patient was treated with CBSCT from an HLA-matched sibling donor after the administration of carboplatin, etoposide, melphalan and abdominal irradiation. The number of nucleated cells in the cord blood was 2.0×10⁷/kg, and that of granulocyte-macrophage colony-forming units 3.8×10⁴/kg. Methotrexate was given on days 3 and 6 as a prophylaxis against graft-versus-host disease (GVHD). The neutrophil count rose to above 500/μl on day 24.The platelet count exceeded 50, 000/μl on day 67, and the last platelet transfusion was on day 60. Grade I acute GVHD was treated with prednisolone, which was discontinued on day 46 without any symptoms of GVHD. On day 43, the patient showed local relapse in the left tibial bone and the right patella, which were irradiated for treatment. However, on day 120, systemic relapse occurred. On day 170, the patient died of cancer. Hematopoietic cells in her bone marrow were detected in those derived from the donor. This case, with previously reported CBSCT cases, encourages us to perform unrelated CBSCT in selected patients through our regional cord blood bank, or the Kanagawa Cord Blood Bank.

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