MDS in children is less common and has less clearcut findings than in adults. To clarify clinical features of childhood MDS, questionnaries were sent to all centers which had the members of the Japanese Society of Pediatric Hematology and the Japanese Society of Clinical Hematology. Data were collected on 165 patients treated between 1981 and 1990. The total group of patients consisted of 87 boys and 78 girls, aged 0-17 years. The distribution among the 5 subgroups of MDS was : RA 69, RARS 4, RAEB 36, CMMoL 13, RAEBT 37 and 6 patients who were difficult to classify. About 30% of patients exhibited bone marrow hypoplasia. Cytogenetic studies in 138 children showed karyotype abnormalities in 75; 35 and 13 had monosomy 7 and trisomy 8, respectively. Because of the generally poor prognosis, a prospective study of childhood MDS in Japan should be considered.

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Regulation of thrombopoiesis was studied in Kawasaki disease (KD). Serum levels of CRP and IL-6 were markedly elevated in the first week of the disease and then rapidly reduced in the second week. Although there was no increase of platelet counts in the first week, a sharp increase of it occurred after reduction of IL-6, up to the maximal level in the second week, and then the counts gradually declined through the third week and later. CFU-Meg was cultured in the medium with the addition of PHA-LCM derived from patients with KD. The relative activities to control PHA-LCM were 1.28±0.20 in the first week, 1.62±0.36 in the second week, 1.58±0.40 in the third week, 0.93±0.20 in the fourth week and 1.22±0.13 in the fifth week concomitantly, showing a peak level in the second to third weeks. To study the activity of the inhibitory factors in thrombopoiesis, IL-3 was added to be the maximal optimal-concentration to the cultured cell line of CFU-Meg, and this was cultured. Count of colony was low in the first week, but increased in the second week, and remained to be a certain level in the third week and later. This might suggest that the inhibitory factors were most potent in the first week and then gradually diminished. It was suggested that IL-6, Meg-CSF (principally, IL-3) and their inhibitors are involved in the change of platelet counts in KD.

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It is known that stomatitis is often observed in children with acute lymphoblastic leukemia (ALL) and it is often the source of ingestion difficulties. An oral rinse may be used to prevent or treat the lesions caused by gingivitis or stomatitis. The purpose of this research was to determine the most effective rinse for use in the treatment of gingivitis and stomatitis among children with ALL at Kobe children's hospital. As a basis for determing the best rinse for use in the treatment of children with ALL, 2 oral symptoms were clinically observed : lesions, their location and their length of duration, and the fluctuation in the amount of bacteria flora. The findings were as follows : 1) Stomatitis was observed in almost all cases. 2) Bleeding from the gingival region corresponded to a decrease in blood platelets in cases which involved the use of anti-leukemic drugs. 3) In almost all cases where etoposide was used, the clinical findings were observed in the gingival region. 4) The total amount of oral bacteria decreased after administration of the antibiotics. 5) In the case of children who have ALL, oral Candidiasis developed more often than in healthy children.

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The lymphoreticular organs, including lymphnodes, spleen and thymus of 43 autopsied cases with hematopoietic malignancies, were histologically and immunohistologically investigated. Immunostain was performed by PAP method using UCHL-1, L26, leukocyte common antigen, S100, immunoglobulins, and so on. In the histological findings, though the basic construction of lymphoreticular organs were preserved, lymphoid follicles of the spleen and the nodes were apparently decreased or diminished and the thymus showed conspicuous involution, associated with fibrous proliferation. Immunohistological findings, especially significant decrease of T cell, B cell and antigenpresenting cell lineage in the spleen and the nodes, suggests suppression of the cell-mediated immunity and also the humoral immunity. These findings in the immunocompromised pediatric patients seemed to correspond with that of severe combined immunodeficient disease.

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In this paper we report on the effect of recombinant human IL-3 on CFU-GM in human umbilical cord blood progenitor cells in liquid culture. The study was conducted using the 2-step culture method. In the 1st, mononuclear cells, including adherent cells, were cultured under serumfree liquid culture conditions, dividing them into those to which rhIL-3 20 ng/ml was added and those to which it was not. We then isolated CFU-GM derived colonies in the presence of G-CSF 20 ng/ml. The CFU-GM derived colonies increased considerably more in the presence of rhIL-3 than in its absence. The CFU-GM derived colonies in 6 serially-tested specimens before and after serum-free liquid culture increased 1.46-2.84 times in response to rhIL-3. No significant difference in effect on the CFU-GM derived colony number increasing action was observed in a liquid culture system supplemented with 10% FBS. The results of these studies demonstrated that the CFU-GM derived colony increasing action is observed even in serum-free liquid cultures, and this appears to be a method enabling more accurate analysis of the effect of rhIL-3 on hematopoietic stem cells.

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A case of idiopathic severe aplastic anemia treated mainly with cyclosporin A is described. A 13-year-old boy was admitted for dizziness, pale face, and petechia on the extremity. His blood counts were as follows : white blood cells 2, 200/μl (neutrophil 23%); red blood cells 1.62×10₆/μl; hemoglobin 5.5 g/dl; platelets 1.8×10₄/μl. These hematological examinations showed pancytopenia. The results of his bone marrow aspiration were as follows : nuclear cells 32, 000/μl; megakaryocytes less than 6.25/, al. He was revealed to have fatty bone marrow. There was no colony formation of erythrocytic series and granulocytic series from his bone marrow cell culture. So he was diagnosed as having idiopathic severe aplastic anemia. As we could not find an adequate donor for the bone marrow transplantation, medication was started. He was successfully treated with cyclosporin A. It was found to be useful reducing the frequency of blood transfusions. And his condition took a turn for the better. The side effects were hirsuteness and reversible kidney trouble. rhG-CSF was used to prevent infection, and the use of erythropoietin was administered to decrease the amount of blood transfusions. Now, it has been about 2 years since he became ill. He can spend his daily life as usual, and the interval between blood transfusions has been much longer than before.

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Two cases of untreated aplastic anemia (severe type) in childhood were treated by recombinant human granulocyte colony stimulating factor (rhG-CSF). In response to rhG-CSF, the first case suspectedly associated with infection showed increase of neutrophils followed by increase of erythrocytes and platelets within two weeks. The other idiopathic case also showed partial response. Furthermore, during rhG-CSF therapy, serum immunoglobulin levels were doubled and T cell subsets were altered in both cases. rhG-CSF appeared to influence the immune system in vivo and to be effective for a certain group of patients with aplastic anemia.

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We report two cases of acute leukemia with pneumatosis intestinalis (PI). A 5-year-old girl with acute lymphoblastic leukemia in relapse presented abdominal pain, abdominal distension, tenderness and decreased bowel sound 14 days after chemotherapy with antileukemic agents. Plain X-ray films showed small bullae along the contour of the bowel, suggesting PI. She was managed with conservative therapy with fasting and antibiotics. Air in the wall of the large bowel disappeared at the 6th day from the onset of PI. The 2nd patient was a 9-year-old girl with acute myeloblastic leukemia, who could not attain complete remission for 4 months from the onset. She developed an acute appendicitis and PI. She received appendectomy, and was treated with antibiotics and leukocyte transfusion, hence her general condition improved. After 10 weeks, PI disappeared, but fistula between the skin and bowel canal remained and she died 5 months after the operation. The stool culture in case 1 grew Enterococcus avium and Pseudomonous aeruginosa, and the culture of pus discharge in case 2 Enterobacter cloacae and Klebsiella pneumoniae. A leukemic infiltration to the bowel and treatments with antileukemic agents such as steroid or cytosine arabinoside might result in a decreased defense mechanism and ulcer formation, followed by microbial infection and PI formation through ulceration.

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A 2-year-old male child case of M4Eo accompanied by hyperleukocytosis was reported. Not less than 10% of eosinophils having specific eosinophilic granules and coarse basophilic granules were contained in bone marrow. Treatments by exchange transfusion, heparin, VP-16 and cytosine arabinoside diminished hepato-splenomegaly and improved blood gas, but caused no change in WBC. The child died of intracranial bleeding fours days after admission.

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Two patients with viral encephalitis complicated by acute lymphoblastic leukemia were diagnosed clinically. Hand-foot-mouth disease preceded in one patient and aphthous stomatitis in the other patient, respectively. Furthermore, herpes simplex virus DNA was detected from cerebrospinal fluid of the second case by polymerase chain reaction (PCR) analysis. PCR analysis is thought to be a useful method for the detection of causative agent of encephalitis which occurs in immunosuppressive individuals including patients with leukemia.

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A case of acute promyelocytic leukemia following etoposide-based combination chemotherapy for Letterer-Siwe disease is reported. The patient was a 3-year-4-month-old girl who had been treated with vincristine, cyclophosphamide, methotrexate, prednisolone and etoposide because of Letterer-Siwe disease diagnosed by bone marrow examination and lymph node biopsy at the age of 5 moths. The total cumulative dose of etoposide was 4, 800 mg/m². She had remained well for 9 months after completion of chemotherapy. Then she came to our hospital with fever and purpura. Bone marrow examination confirmed a diagnosis of acute promyelocytic leukemia. The bone marrow karyotype was 46, XX, t (15; 17) (q22, q12). She was treated with BFM-83 protocol and attained remission after induction chemotherapy. But she died of heart failure after one year of consolidation chemotherapy. The risk of developing secondary leukemia in high-dose etoposide therapy is discussed.

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A 5-year-old boy presented with a history of left postauricular mass (20 mm × 17 mm). The tumor was an enlarged lymph node and was completely resected. Histological diagnosis was Non-Hodgkin's lymphoma, lymphoblastic type, by Japanese Lymphoma Study Group class. An immunophenotyping analysis of frozen tissue sections revealed that tumor cells showed HLA-DR⁺, CD 10⁺, CD 19⁺, CD20^- and CD34^- indicating that they classified to pre-B-cell phenotype. Bone marrow contained 22.3% atypical lymphocytes with basophilic nuclei, dusky chromatin, and scanty cytoplasm, but not convoluted nuclei. Immunophenotyping of marrow mononuclear cells revealed that about 30% of cells had the same surface markers as tumor cells of the resected lymph node. He was treated with chemotherapy designed for intensive high-risk acute lymphoblastic leukemia (CCLSG 874), and has now been in complete remission for 6 months after induction chemotherapy. Previous reports with pre-B-cell lymphoblastic lymphoma including our case were also reviewed.

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A 14-year-old girl with neurofibromatosis type-1 complicating with the cecal non-Hodgkin's lymphoma is reported. She was referred to our hospital because of an abdominal mass, and was found to have a solid tumor of the cecal region, 4 cm in diameter, by ultrasonographic examination. Recurrent ileo-cecal intussusception occurred after admission. Precise barium enema study demonstrated two mass defects, 4.5 cm and 2.0 cm in diameter, of the cecal region. The cecum including tumor was widely resected with ileo-colonic anastomosis. Histological diagnosis was non-Hodgkin's lymphoma, diffuse medium-sized cell type (LSG class). The tumor cells showed CD 10⁺, CD 19⁺, CD20⁺, HLA-DR⁺, cytoplasmic, μ⁺, and surface IgM⁺ by immunophenotyping analysis, indicating that they were classified to the mature B-cell phenotype. Previous reports of neurofibromatosis type-1 with malignant lymphoma including our case were also reviewed.

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A fifteen-year-old girl with acute nonlymphocytic leukemia (M4) is reported on. She was in first complete remission for one year. In July 1991, after the scheduled consolidation chemotherapy, she had severe myelosuppression. This was further complicated by bilateral pneumonia. In spite of aggressive antibiotic therapy including antifungal agents, the pneumonia did not improve. About one month later, she suddenly complained of severe dyspnea and chest pain. She went into a critical condition with cyanosis, hypotension, and cardiac arrest. At the autopsy, multiple fungal balls and infiltrations of aspergillus were found in her lungs. Moreover, a massive hemothorax (the volume was about 3, 600 ml) was revealed. Also, the left subclavicular artery was ruptured by invasive aspergillosis.

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An 11-year-old boy with chronic mucocutaneous candidiasis (CMC) received allogenic bone marrow transplantation (BMT), with marked improvement in symptoms and immunological findings. The patient had recurrent thrush from age 2 months and was diagnosed as having CMC at age 4 months. He showed many episodes of bacterial respiratory infections, growth retardation and circulatory disturbance of his right leg due to aortitis from age 10. BMT was performed from his 9-year-old HLA-identical brother as a donor and with busulfan 4 mg/kg/day × 4 days and cyclophosphamide 50 mg/kg/ day × 4 days in the conditioning, methotrexate and cyclosporine in the prophylaxis for GVHD. Oral amphotericin B and intravenous fluconazole were administered to prevent exacerbation of candida infections. Recombinant human G-CSF was also administered. He recovered without any problems and attained neutrophils more than 500/μl on day +12. From day +20, thrush disappeared and on day + 77 the patient showed an improved lymphocyte blast formation against Candida albicans.

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A 4-year-old-boy with two kinds of complex hemostatic defects, type IIA von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia (HHT), was reported. He was admitted with the complaint of paleness due to severe anemia. Telangiectatic lesions were detected in his face and anterior thoracic wall. Laboratory tests of blood coagulation revealed decreased factor VIII coagulant (VIII : C), ristocetin cofactor (RCoF) and von Willebrand factor antigen (vWF : Ag) levels, as well as the impairment of aggregation of platelets in response to epinephrine and ADP. Evidence for von Willebrand disease was found in his father and younger sister. Telangiectatic lesions were also detected in his father. Impaired aggregation of platelets was found in his younger sister. Family study suggested that the two traits appeared to have been inherited together, therefore the strong association between vWD and HHT might be postulated.

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We treated an azidothymidine (AZT) -refractory AIDS patient with dideoxyinosine (ddI). This is a 15-year-old boy with hemophilia A. Anti-HIV antibody has been positive since 1985. He suffered from pneumonia in April 1989 and was treated with antibiotics and sulfamethoxazole-trimethoprim (S-T). Absolute CD4 positive cells (CD4) were 59/μl at that time and we started oral AZT 100 mg every 6 hours. After 17 weeks, CD4 count increased up to 326/μl. However, CD4 count decreased to 60/μl after 24 weeks. He complained of dyspnea in June 1990. CD4 count was 16/μd. We made a diagnosis of Pneumocystis carinii pneumonia based on the diagnostic criteria of the AIDS Surveillance Committee of Japan Government. We treated him with S-T and pentamidine. On admission, HIV was cultured from his peripheral blood and the HIV was still proliferating even in coculture with AZT (1.0 μM). DNA analysis of the HIV strain showed such mutation in reverse-transcriptase gene as seen in AZT-resistant HIV strain reported by Larder et al. So we diagnosed this case as refractory to AZT. In other words, he was refractory to AZT therapy clinically and through in vitro study as well as gene analysis. We stopped AZT and started ddI 167 mg every 12 hours. His CD4 count transiently increased to 70/μl after 16 weeks. He has been doing well for 21 months. His CD4 count is 5/μl, with no peripheral neuropathy. Karnofsky score is 100%.

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A one-year-old girl was diagnosed as having Philadelphia chromosome-positive chronic myelogenous leukemia, which was successfully controlled with interferon-a alone. She was in the chronic phase for two years. However, Philadelphia chromosome in her bone marrow cells had not reduced. Two years after the diagnosis, she received allogeneic bone marrow transplantation (BMT) from an HLA-identical, 12-month-old sister. Preparative regimen consisted of busulfan 4 mg/kg/day ×4, cyclophosphamide 60 mg/kg/day × 2. Cyclosporine A and methotrexate were used for the prophylaxis of GVHD. Her blood type became identical with that of the donor at day +180 posttransplantation. Currently 4 years old, she remains free of disease.

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Two siblings, a 2-year-3-month-old boy and a 14-day-old boy, who were afflicted with infantile genetic agranulocytosis (Kostmann Type) received different methods of treatment with rhG-CSF. Each patient was closely observed so as to monitor any differences in the response to the treatments. Specifically we looked at changes in their clinical symptoms and subsequent levels of neutrophils following their treatments. The rhG-CSF was administered to the patients in the following ways continuous intravenous infusions over a period of 24 hours, intravenous infusion for an hour, and subcutaneous injection. In both patients we observed rapid appearance of neutrophils and marked improvement of their clinical symptoms. The patient who received continuous infusion of rhG-CSF over a 24-hour time span showed an increase in the number of neutrophils and an improvement in CRP. We conclude that further study regarding the proper administration of rhG-CSF should focus on the relationship between the number of neutrophils and the concentration of rhG-CSF in the serum at the time of each administration.

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A case of biphenotypic acute lymphoblastic leukemia coexpressing CD2 and CD19 antigens is reported. The patient, a 12-year-old boy, had generalized, remarkable, lymphadenopathy, especially at cervical, axillar, paraaortic, and inguinal regions. The peripheral leukocyte counts were 5, 000/μl with 58.0% blasts. Bone marrow was occupied with 97.5% large or small blasts with lymphoid appearance. The surface marker analysis by two-color flowcytometry revealed that the blasts were positive for both CD2 and CD 19 at single cell level. The rearrangement of IgH and TCR-β genes were both detected. After responding to our protocol for high risk group ALL, he has achieved a complete remission and remains free of disease for eighteen months.

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