The hemophagocytic syndrome (HPS) includes malignant histiocytosis (MH), familial erythrophagocytic lymphohistiocytosis (FEL), and virus-associated hemophagocytic syndrome (VAHS). Clinically, the patients with HPS demonstrate persistent fever, weight loss, pancytopenia, hepatosplenomegaly, and disseminated intravascular coagulopathy. These symptoms reflect hypercytokinemia elicited by activated T lymphocytes and macrophages. An overproduction of cytokines may be caused by either neoplastic cells in MH or abnormal immunological responses to various antigenic stimuli in VAHS/FEL. Recent research has shown that true histiocytic malignancies are rare and that the majority of cases of MH is associated with malignant lymphoma.

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We examined mean platelet volume (MPV) and platelet distribution width (PDW) in children with idiopathic thrombocytopenic purpura (ITP) and with various kinds of thrombocytosis. MPV was remarkably small at the onset of acute ITP and large during recovery phase. MPV normalized when platelet count reached the normal level. MPV and PDW was large at a low platelet count level in children with chronic ITP and normalized as the platelet count increased to the normal range. There were many cases of thrombocytosis in newborns and infants which occurred in conjunction with infectious disease, respiratory disease, hematological disorder, surgery, bleeding and chemotherapy of malignant tumors. Under these conditions the MPV was found to be significantly low and the PDW in the normal range.

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We examined platelet counts, mean platelet volume (MPV) and platelet distribution width (PDW) in children with acute leukemia and aplastic anemia. The MPV after the cessation of therapy in children with acute leukemia was slightly smaller than in healthy children, but the PDW was normal. After intensive chemotherapy the MPV of children with acute leukemia significantly decreased. Before the platelet count recovered to the normal level, the MPV had increased. This seems to be one index of bone marrow recovery. When the platelet count increased to the normal level, the MPV was significantly small, but the PDW was still wide. It is suspected that this is due to the effects of antileukemic drugs on the production of platelets. When the platelet count was 10-20×10³/μl in children with aplastic anemia, the MPV was small. When the platelet count increased to over 50×10³/μl, the MPV reached the normal level. The PDW was usually large.

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We studied the effects of colony-stimulating factors on erythroid progenitors, the production of hematopoietic factor and the dynamics of progenitor cells in premature and mature infants. Colonies of burst-forming unit-erythroids of the cord blood of premature and mature infants increased in response to interleukin-3 and erythropoietin. The burst-promoting activities of cord blood of premature and mature infants were significantly lower than those of adults. Erythroid progenitors of the cord blood of premature infants were more significantly increased than those of mature infants. There was no significant difference between the erythropoietin sensitivity of the cord blood of mature infants and the peripheral blood of premature infants.

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Peripheral blood examinations were performed 1 month after birth in 621 neonates. Test values were compared between groups classified according to birth weight. When birth weight was low, hemoglobin (Hb) concentration tended to be low. The white cell count tended to be significantly lower in the low-birth-weight group. The 621 neonates were also divided according to Hb concentration, and their mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and white cell count were compared. There were no differences in MCV or MCH between the groups. Testing for the relationship between Hb concentration and the white cell count showed that the white cell count tended to be low when Hb concentration was low. These results suggest that in cases of neonatal physiologic anemia, the lower the hematopoietic activity, the lower the birth weight, regardless of maturity or immaturity, and the higher the activity, the higher the birth weight. The white cell count in this period was also believed to reflect hematopoietic activity.

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The in vitro production of tumor necrosis factor-α, (TNF-α) induced by the streptococcal preparation, OK432 was examined to assess the monokine production of leukemic blasts obtained from patients. The producing cells of TNF-α in normal peripheral blood were monocytes stimulated with OK432 or 12-O-tetradecanoyl-phorol 13-acetate (TPA), although both lymphocytes and monocytes were stimulated with phytohemagglutinin (PHA) and produced TNF-α. The capacity of the leukemic cells from 43 patients with acute lymphoblastic leukemia (ALL), 18 with acute non-lymphocytic leukemia (ANLL) and 2 with chronic myelogenous leukemia (CML) to produce TNF-α was investigated in the present study. Leukemic blasts from only 7 out of 43 ALL patients produced relatively small amounts of TNF-α. These patients included 4 cases of common ALL, 2 of undifferentiated type ALL and 1 of. B-cell ALL. Two of seven cases expressed myeloid antigens on leukemic blasts. Two cases of undifferentiated type ALL were under one year of age. 18 cases of ANLL, 2 of 3 M1 cases and 1 of 3 M2 cases showed distinct production of TNF-α. All cases of M4 (6 cases) and M5b (4 cases) revealed large amounts of TNF-α production. None of M5a (2 cases) secreted TNF-α in vitro. Both cases of CML showed small amounts of TNF-α production. The production of TNF-α by leukemic blasts was well correlated with the expression of monocyte-specific CD14 antigen. TNF-α, production in childhood leukemia may be characteristic of leukemic blasts with monocytoid differentiation.

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We report two cases of Down's syndrome with acute megakaryoblastic leukemia, who remain in continuous complete remission following the cessation of therapy. Patient 1 was a 25-month-old girl and Patient 2 was a 21-month-old boy. Blasts in both patients were positive for monoclonal antibodies recognizing platelet associated antigen (CDw41 and CDw42) and for platelet peroxidase by analysis with electron microscopy. Chemotherapy regimen in Patient 1 consisted of cytocine arabinoside 100 mg/m² for 7 days and daunomycin 30 mg/m² for 2 days. In addition, VP-16 150 mg/m² was given to Patient 2 for 3 days. After being treated with eight courses of the chemotherapy for eight months, both patients have been given follow-up examinations without chemotherapy. Complete remissions were obtained after two courses of chemotherapy in Patient 1, and after three courses in Patient 2. They have remained in complete remission for 36 months (Patient 1) and 17 months (Patient 2) since the cessation of therapy.

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It is rare for hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) to occur in members of the same family at the same time. We report two cases of HUS/TTP who were successfully treated with high-dose γ-globulin and gabexate mesilate (FOY®). Case 1 : A 5-year-old girl was admitted to our hospital because of bloody diarrhea. On admission, the peripheral blood analysis revealed leukocytosis without anemia and thrombocytopenia. Gastrointestinal symptoms were improved with antibiotics. Five days later, however, her laboratory tests demonstrated Hb 9.7 g/dl, platelet 29 × 10³/μl, WBC 14, 600/μl with 71.0% neutrophils, BUN 30.9 mg/dl and creatinine 0.8 mg/dl. Urine sediment had numerous red cells and the peripheral blood picture revealed marked fragmentation of red cells. Both direct and indirect Coombs tests were negative. Based on the data, a diagnosis of HUS was made. She was treated with gabexate mesilate (FOY®) and high-dose γ-grobulin infusion. The platelet count and BUN were normalized by the 5th day of γ-globulin administration. Case 2 : A 77-year-old male, the grandfather of Case 1, had ileocecal pain when Case 1 was admitted. Shortly after admission, he showed acute abdominal symptoms and underwent surgery. The diagnosis was ischemic enterocolitis. After 8 days, he developed symptoms related to anemia, thrombocytopenia and neurological manifestations, including convulsion and dementia. Initially FOY was administered under the diagnosis of DIC, and the platelet count temporarily increased. Highdose γ-gibulin therapy was started, and the neurological signs and laboratory data were improved significantly. Our experience shows that HUS and TTP might be variable expressions of a single clinical entity and high-dose γ-grobulin therapy could be an effective treatment for HUS/TTP.

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A 1-month-old male infant was admitted to our hospital for petechiae over the extremities. Physical examination showed a firm mass at the left upper part of the abdomen. Laboratory findings were; hemoglobin 6.0 g/dl, platelet count 4, 000/μ1, prothrombin time 18.0 sec (control 11.3 sec), activated partial thromboplastin time 57.0 sec (control 33.6 sec), fibrinogen 33 mg/dl, and fibrinfibrinogen degradation products 40 μg/ml. Because ultrasound, CT, MRI scans and angiography suggested a pancreatic hemangioma, Kasabach-Merritt syndrome was diagnosed. Unresponsive to treatment with prednisolone, gabexate mesilate and heparin, thrombocytopenia and hypofibrinogenemia persisted, and the tumor size remained unchanged. Soon after the initiation of alternating pulse methylprednisolone and high-dose intravenous γ-globulin therapy, platelet counts rapidly increased. During the treatment platelet antibody became negative, and platelet-associated IgG (PAIgG) decreased in an inverse relation to platelet counts. Subsequently blood coagulation data returned to normal, and the mass gradually reduced in size. The histology of biopsied tumor specimens proved the illness to be capillary hemangioma. Further regression of the mass was achieved by continuation of the therapy.

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A case of transient abnormal myelopoiesis (TAM) with myelofibrosis was reported. A 1-month-old male with Down's syndrome was admitted to our hospital because of hepatosplenomegaly and jaundice. The WBC count of peripheral blood increased to 69, 000/μl with 60% blasts, but neither anemia nor thrombocytopenia was recognized. Bone marrow examination showed the presence of 15% blasts cells. In cytochemical studies, a large number of blasts were peroxydase negative, naphtal AS-D chloroacetate esterase negative, α-naphthyl butyrate esterase negative and acid phosphatase positive. Fresh blood cells reacted to monoclonal antibodies and recognized platelet-associated antigen (pI-gpIIb/IIIa). The blast cells were positive for platelet peroxidase (PPO) on analysis by electron microscopy. We hypothesized that TAM evoked leukocytosis and no therapeutic measurement was applied. The blast cells gradually subsided in the peripheral blood. At that time, the bone marrow biopsy showed a marked fibrosis with no blast cells, and hepatic biopsy did not showed blast infiltration. The patient died when 60-days old because of hepatic complication. To establish the disease entity, further studies of many cases by cytochemical, immunological, and ultrastructural microscopic examination are necessary.

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An infantile case of common ALL with extreme hyperleukocytosis is reported. A 6-month-old female was admitted to our hospital because of hepatosplenomegaly and marked hyperleukocytosis. The white blood cell count at diagnosis was 1, 753, 000/μl. She was diagnosed as FAB-L1 on the basis of negative myeloperoxidase and partially granular positive periodic acid-schiff staining. Surface marker analysis revealed that the blasts were positive for CD10 and CD19. Rearrangement of the immunoglobulin heavy chain gene was detected. In addition, chromosomal analysis of peripheral blood revealed +der (19) t (19; ?) (p13; ?). We performed exchange transfusion using 1, 200 ml (160 ml/ kg) of group O red blood cells with group AB fresh frozen plasma and the WBC count after exchange transfusion was 263, 000/μl. Chemotherapy, including vincristine, prednisolone, daunorubicin and Lasparaginase was initiated immediately. No metabolic abnormalities or bleeding complications appeared. She has been in complete remission for 20 months since the diagnosis.

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A 10-year-old-girl complaining of a hoarseness of voice for one month was admitted to our hospital. Otolaryngologic examination showed a granular mass arising from right false cord. The histology of tissue taken from the mass revealed non-Hodgkin's lymphoma, with a diffuse mediumsized cell type. No evidence of disease had been found elsewhere in the body. She was successfully treated with CHOP therapy and 40 Gy of irradiation. Non-Hodgkin's lymphoma of the larynx is a rare occurrence in children. The disease is curable when early diagnosis and therapy are instituted. Long-term hoarseness may be an early sign of malignant lymphoma of the larynx.

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Two cases with childhood Ki-1 lymphoma were reported in this paper. An eight-year-old female (Case 1) had a stage III lymphoma of tracheo-bronchial origin. She had a resection of the tumor, chemotherapy for 3 years and survived for 6 years. A six-year-old female (Case 2) had an abdominal lymphoma also involving mediastinum and cervical lymph nodes (stage III). She had a biopsy of the tumor, chemotherapy for 3 years and survived for 4 years and 7 months. These cases were diagnosed as malignant lymphoma (diffuse, large cell type in the LSG classification) that also had the histologic characteristics of an anaplastic large cell lymphoma, positivity for Ki-1 antigen (CD30), and no specific cell marker. So far, thirty-eight cases of childhood Ki-1 lymphoma have been reported in the literature. Clinical findings indicate they have a high occurrence rate in the older child, skin involvement (one third of the cases), good response to chemotherapy and a favorable prognosis.

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A 4-year-old boy was diagnosed in September, 1983 as having acute lymphoblastic leukemia (ALL) with 1 ; 19 translocation. Complete remission was obtained with VPL (vincristine, prednisolone, and L-asparaginase) therapy. Afterwards he received intrathecal administration of methotrexate and Ara-C (12 mg/m², 20 mg/m² × 6), and whole-skull irradiation (2, 000 rad) for prophylaxis of CNS leukemia. Unconsiousness and convulsion developed 5 months after the onset of the treatment. Computed tomography and EEG demonstrated leukoencephalopathy. A survey of the literature, including our case, demonstrated a total of 3 ALL cases with 1; 19 translocation having a leukoencephalopathy during early remission. Some ALL cases with 1 ; 19 translocation may have a leukoencephalopathy following standard prophylactic therapy for CNS leukemia.

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A cases of severe aplastic anemia (SAA) that transformed to myelodysplastic syndrome (MDS) with 7-monosomy and finally to acute leukemia is presented. The patient was first diagnosed as SAA at 5 years of age in October 1986. He did not respond to various conventional treatments. In May 1989, when he had severe infection he received high-dose rhG-CSF (KRN 8601 up to 1, 200 μgl m²) for 8 weeks. There was a remarkable monocytic response, but it fluctuated thereafter. In November his bone marrow showed normal cellularity with 12.6% myeloblasts, which is comparable to MDS. Chromosomal analysis revealed 48, XY, -7, +10, +21, +22. At the beginning of 1990 MDS changed into overt leukemia and he expired in April. It is unclear whether he had clonal abnormality since the onset of aplastic anemia or additional clonal abnormality induced by such treatments as androgen, antilymphocyte globulin (ALG), and rhG-CSF. There is a good chance that the rhG-CSF switched on the development and growth of the 7-monosomy clone in this patient.

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A boy with familial erythrophagocytic lymphohistiocytosis (FEL) is reported. His two siblings had died of the same disease. He was diagnosed at the age of 1 month and was treated with an exchange transfusion and chemotherapy consisting of VP16, prednisolone and intrathecal methotrexate. He attained complete remission. Four months later in remission, he received bone marrow transplantation (BMT) from an HLA-identical brother. The conditioning for BMT included intrathecal methotrexate 12 mg/m²/day×1, busulfan 4 mg/kg/day×4, VP16 60 mg/kg/day×1, cyclophosphamide 60 mg/kg/day×2 and anti-human lymphocyte globulin (AHLG) 30 mg/kg/day×3. cyclosporin A and MTX were used for the prophylaxis of GVHD. After BMT leukocytes counts increased to more than 1, 000/μ1 by day+18, and his blood type became identical with that of the donor at day+50. Grade 2 GVHD was treatable with prednisolone. His NK cell activity was very low at the onset of the disease, but improved after the transplant. Currently over 3 years old, he remains free of disease.

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