Recent progress in molecular biology has led to the discovery of novel genes which reside in the vicinity of the breakpoints of chromosome abnormalities in childhood acute lymphoblastic leukemia (ALL). Chromosome abnormalities were divided into three groups : (1) translocation, (2) deletion, (3) increase of chromosome number groups. Among the translocation group, novel genes on donor chromosomes were cloned using rearrangement of immunoglobulin heavy chain genes in B-lineage associated 14q32 translocations, and rearrangement of T-cell receptors in T-lineage associated 14q11 and 7q35 translocations, respectively. Recently t (1 ; 19), which was associated with pre-B phenotype, has been studied molecularly. In addition to previous data of t (8 ; 14) and t (9 ; 22), new interesting data was found and its clinical association is controversial. Among the deletion group, recessive oncogenes were presumed on 9p, 6q, and 12p. The regions of chromosome abnormalities are a good place to search for a number of genes which seem to be associated with development or advance of ALL in children. Moreover, a number of genes will be identified and their structure and gene products will be searched. Prevention and cure of ALL can be expected in the near future.

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Since the myelodysplastic syndrome (MDS) usually occurs with elderly patients, there have been few reports describing the syndrome during the childhood period. But recently, pediatric hematologists clearly recognize that MDS is less rare than was previously thought. Childhood MDS is diagnosed on the classification of the French-America-British Cooperative Study Group (FAB) but we still have such cases with hematopoietic dysplasia which are difficult to classify by the FAB system. The classification of ill-defined dyshematopoiesis has not been widely accepted yet but is considered to be very useful to observe and treat patients with unexplainable cytopenias. We reported ten childhood cases that correspond to the criteria of ill-defined dyshematopoiesis and analyzed their hematological features. Six patients out of ten developed leukemia after four months to nine years. Elevated serum levels of LDH (above 400 IU/l) and especially elevated LDH II ratio at the onset may be a factor for predicting leukemia development. More data regarding the MDS and ill-defined dyshematopoiesis in children is obviously needed.

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Twenty-three infants (under one year old) with acute leukemia were studied for immunological and cytogenetic characteristics. Thirteen patients were diagnosed as acute lymphoblastic leukemia (ALL) and ten were acute non-lymphocytic leukemia (ANLL). In 11 cases among the 13 ALL patients, the leukemic blasts did not express CD10 (J5). Two out of 11 patients had leukemic cells with concomitant expression of CD13 (MY7) and. CD19 (B4) antigens, and they eventually underwent remarkable changes in morphology from (FAB) -L1 to M5b at relapse. In four other cases, the leukemic cells disclosed additional expression of CD13, CD14 (MY4), and CD33 (MY9) antigens after short-term culture, although the blasts of the remaining five cases were not altered phenotypically by the treatment, and stayed only HLA-DR and CD19 positive. Ten ANLL cases were classified as 6 monocytic or myelomonocytic and 4 megakaryocytic leukemias. Cytogenetic analyses were carried out in 15 cases. Translocations involving 11q 23 site were identified in 8 of 9 ALL and 3 of 6 ANLL patients. Two megakaryocytic leukemia cells showed trisomy of No. 21 chromosome. These observations imply that acute leukemia in infancy is a distinctly heterogeneous disease in phenotypical respects, but that in the majority of cases, except megakaryocytic leukemia, biphenotypic features were demonstrated. The leukemic cells of infant leukemia may be of stem cell origin with a potential for lymphoid, myeloid, and conclusively monocytic differentiation.

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Two cases of allogenic bone marrow transplantation (BMT) for children with Philadelphia chromosome (Ph¹) -positive acute lymphoblastic leukemia were reported. The first case was a 13-year-old boy who received BMT from an HLA genotypically identical brother in the first remisson. The second case was a 7-year-old boy who received BMT from an HLA-A, B, and DR matched and MLC positive mother in the third remission. In this latter case, chromosomal analysis revealed that chromosome of leukemic cells in the first admission was normal, but chromosome at the first bone marrow relapse was Ph¹-positive. He relapsed again in central nervous system (CNS) at 3 months of second complete remission (CR), and BMT was done following the therapy of CNS leukemia. The first case was conditioned with cyclophosphamide (CY) 60 mg/kg×2, araC 3 g/m²×3, and total body irradiation (TBI) 10 Gy. The second case was conditioned with CY 60 mg/kg×2, araC 3 g/m²×4, and TBI 10 Gy plus 6 Gy of craniospinal irradiation. The first case received cyclosporine A (CyA) and the second case received CyA and methotrexate for graft-versus-host desease (GVHD) prophylaxis. The first case had grade II of acute GVHD, chronic GVHD, and interstitial pneumonia, and is free of leukemia at 39 months after BMT with 100% Karnofsky performance scale. The second case had grade I of acute GVHD, chronic GVHD, and is free of leukemia at 8 months after BMT. Allogenic BMT for children with Phi-positive ALL should be done if a suitable marrow donor is available.

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Recombinant human granulocyte colony stimulating factor (rhG-CSF) was administered to 18 neutropenic children to evaluate its effect. RhG-CSF was given intravenously or subcutaneously at the doses of 50-178 μg/m². In five cases of congenital agranulocytosis and two cases of aplastic anemia, the peripheral neutrophil counts above 500/μl were observed for 15.9±6.6 days in the 28-day rhG-CSF treatment period, compared to 0 days in the 28-day control period (p < 0.01). In seven cases with solid tumor receiving chemotherapy, the recovery of white blood cell counts was accelerated by rhG-CSF and exceeded 2, 000/μ1 at 12.8±2.6th day versus 17.8±2.5th day in the control (p<0.01). Beneficial effect of rhG-CSF for terminal ALL and CML patients was not obtained. In this study, no adverse effect of rhG-CSF was observed.

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Twenty-six children with non-Hodgkin's lymphoma were treated between 1977 and 1988. Fifteen of them were treated with CHOP, COMP, and LSA5L2 protocol before 1984, eleven were treated with CCLSG protocols (NHL-8201, NHL-855) after 1985 until 1988. Induction rate was 85%; overall failure-free survival rate was 45%. There were no relapses after 17 months since treatment started. Eighteen of the 26 patients were in advanced stages : stages III, IV : ten who were treated before 1984 relapsed in 17 months; failure-free survival rate of eight who were treated after 1985 until 1988 was 45%. Of eight relapsed children, 5 were lymphoblastic type; these 5 died of the diseases. Two of the rest were small non-cleaved types; the other was diffuse large cell type. Two lymphomas, one small non-cleaved type, and one diffuse large cell type have survived twelve and sixty-one months. In conclusion, there are some difficulties in improving the prognosis of pediatric lymphomas, especially lymphoblastic lymphomas.

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A case of non-Hodgkin's lymphoma of the bone, which originated in the left humerus, metastasized in the right humerus and the left femur was reported. A five-year-old girl was admitted to our hospital because of bulging of the left upper arm. The bone marrow and the peripheral blood were not involved by the neoplastic cells. A skeletal survey showed multiple osteolytic lesions and bone membrane reactions on the left humerus. The surface marker analysis of the biopsy specimens on the left humerus revealed that tumor cells were positive for common ALL antigen. The surface marker analysis of biopsy specimens on the right humerus and the left femur regions suspected to be involved in the skeletal survey, also revealed common ALL phenotype. She has been in remission for 48 months after diagnosis.

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We reported a case of a 17-year-old boy with severe aplastic anemia complicated with liver cirrhosis induced by post-transfusion hepatitis and secondary hemochromatosis. B3cause of refractory anemia, he received many blood transfusions, and died of hepatic failure. At autopsy a large amount of hemosiderin deposition was found in the liver, pancreas, spleen, adrenal cortices, thyroid gland, stomach, and colon. There was marked lymphocyte infiltration in the liver, which was considered to be due to hepatitis. The liver also showed mild fibrosis with hemosiderin deposition in Kupffer cells. It is suggested that post-transfusion hepatitis was aggravated by secondary hemochromatosis, and developed liver cirrhosis.

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A case of posterior mediastinal T-cell lymphoma presenting with epidural spinal cord compression is reported. A five-year-old girl was admitted to our hospital because of backache, muscle weakness and paresthesia of lower extremities, and urinary and fecal incontinence. Chest X-ray showed a paravertebral tumor and a myelogram revealed a complete block at the level of Th9. MRI also demonstrated a paravertebral tumor invading the spinal tube through the intervertebral foramen. Because of rapid progression of spinal cord compression symptoms, an emergency laminectomy was per-formed. A biopsy of the tumor was done concomitantly. A paravertebral tumor invading the epidural space through the intervertebral foramen was observed at operation. Light microscopic examination of the biopsy specimen showed a small round cell tumor, and immunocytochemical examination demonstrated a T-cell lymphoma with positive MTI. The paravertebral tumor completely dis-appeared soon after treatment with combination chemotherapy and the symptoms of spinal cord compression improved. She has been disease-free for more than six months.

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An infantile case of combined autoimmune neutropenia and thrombocytopenia is reported. A 5-month-old boy was referred to our department because of petechiae over the whole body. Hematological examination showed a white cell count of 6, 000 cells/μl with severe neutropenia and thrombocytopenia (2, 000 platelets/ μl). Bone marrow aspiration revealed normocellularity (16.9 x 10⁴ cells/ μl) with a normal megakaryocyte count (90 cells/μl). However, platelets adhering to megakaryocytes and percentage of segmented neutrophils were decreased in May-Giemsa stain of bone marrow specimens. An increase of toxic granules in the cytoplasm was also observed. Immunological examination showed positive findings for platelet-associated IgG and neutrophil-binding IgG. A diagnosis of autoimmune neutropenia with thrombocytopenia was made, and therapy with prednisolone and intact-typed γ globulin was started. The platelet count immediately improved, but the neutrophil count did not increase until 20 days. He was discharged from the hospital after 3 months of treatment. However, bleeding tendency and recurrent infection were often seen.

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We reported a case of Ph¹-positive acute leukemia whose blast cells had both lymphoid and myeloid phenotype. The leukocyte count of peripheral blood was 33.4 × 10⁴/cmm. Seventy- one percent of the cells were blasts with myeloid appearance (FAB, M₂ type). Bone marrow was occupied with 71.8% blasts cytochemically positive for myeloperoxidase. Cytogenetic marker was Ph¹ chromosome. Surface markers analysis revealed that the blast cells were positive for Ia, CD 19 (B₄), CD10 (CALLA), CD33 (My₉). J₅ and My₉ were simultaneously expressed on the same blast cells by two-color flowcytometry. In addition, rearrangement of heavy chain of immunoglobulin gene was detected. This acute leukemia was considered to occur at the level of uncommitted multipotential progenitor cell of both lymphoid and myeloid cells. He was treated with doxorubicin, vincristine, L-asparaginase, and prednisolone, and obtained complete remission.

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Three children with chronic idiopathic thrombocytopenic purpura (ITP) were treated by repetitive (monthly) high-dose (1 g/kg) intravenous gammaglobulin, which was started 4-6 years after the onset of ITP. Excellent effects were observed in 2 cases 5-6 months after initiation of therapy and they remained in complete remission for more than 2years. In the third case, the elevation of platelet counts was transient, though bleeding tendency was markedly relieved. Immunologically, platelet-associated IgG, natural killer (NK) cell activity, and lymphokine activated killer (LAK) cell activity were normalized by high-dose gammaglobulin therapy in all three cases, though the effects were transient in the third case in whom consistently elevated CD8+HLADR+ (activated T suppressor) lymphocytes and inverted CD4/CD8 ratio were observed. Headache of short duration was the only adverse effect, in the first case. We would like to emphasize that monthly high-dose (1 g/kg) gammaglobulin therapy in effective in treating chronic ITP both clinically and immunologically, and complete remission may be attained by this therapy.

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