Many of the congenital disorders of platelet function are known to be caused by the lack and/or abnormality of platelet membrane glycoproteins. Flow cytometry using FITC labeled monoclonal antibodies against platelet glycoprotein can be used to analyze the amounts or abnormalities of these platelet glycoproteins and is useful for the diagnosis of these diseases. Expecially, in thrombasthenia and Bernard-Soulier syndrome, the assay of the amounts of platelet glycoproteins using flow cytometry is useful not only for diagnosis of the disease but for carrier detection and prenatal diagnosis. In addition to the quantitation of the amounts of these glycoproteins, flow cytometry can be used for platelet functional analysis, such as fibrinogen binding assay, for identifying the presence of activated platelets, and for functional or quantitative analysis of recombinant platelet-related proteins expressed on the cell surface. Flow cytometric analysis of the congenital disorders of platelet function is a simple and quick method and can be used to assay many patients using small amount of samples. It is able to analyze individual cells without repeated washing, which might cause degradation of platelet proteins. With the development of new specific monoclonal antibodies, the use of flow cytometry in the field of congenital platelet function disorders will be increasing.

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Evaluations on the growth and endocrine functions with 6 children, who underwent peripheral blood stem cell autografts (PBSCT) without the use of preparative total body irradiation (TBI) and have been surviving over 1 year, were performed. Examinations performed were : tolerance tests for insulin, luteinizing hormone releasing hormone (LH-RH) and thyrotropin releasing hormone (TRH). Simultaneous measurements of the basal levels of serum thyroid hormone (T3, T4), testosterone, somatomedin-C (Sm-C), and urinary growth hormone (U-GH), as well as determination of the bone age, were also performed. Abnormal secretions of GH, LH, and FSH upon stimulation and decreased levels of serum Sm-C, testosterone, and urinary GH were found in one patient who received local ir-radiation therapy on the skull and testes for leukemic involvement. Growth-spurt delayed in this patient, but subsequent supplemental therapy with testosterone resulted in successful catch-up growth. However, in the remaining patients, no abnormality was disclosed. The preliminary results may suggest that growth and endocrine functions of children who underwent high-dose chemotherapy without irradiation protocol will be kept intact.

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We studied hepatitis C virus (HCV) antibodies in 130 cases of multitransfused children with hematologic or oncologic disorders by the Ortho ELISA system, and analyzed clinical features of the seropositive 23 cases (17.7%). Eleven cases (8.5%) have been persistently seropositive for HCV antibodies for 8 to 18 months. Their liver function tests have been constantly or intermittently elevated independently of the chemotherapy, and all the cases developed non-A non-B hepatitis 3 to 56 months after their initial blood transfusions. On the other hand, HCV antibodies in the other 12 cases returned to negative sequentially. Their liver function test results worsened transiently during the chemotherapy, but returned to normal rapidly after the therapy. We consider that the former 11 cases have suffered from hepatitis C, but that the results of HCV antibodies in the latter 12 cases may have been false-positive based on their clinical courses. The liver function test results in two of the seropositive 11 cases returned to normal during the chemotherapy and the HCV antibodies in one of them became positive at 28 months after the development of hepatitis. These results suggest that multitransfused children with hematologic or oncologic disorders have a substantial risk for hepatitis C infection and immunosuppression related to the chemotherapy may influence the clinical course of HCV infection, leading to the transient normalization of liver functions and delayed appearance of HCV antibodies.

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Twenty-four totally implantable catheters were inserted in twenty-two pediatric patients mainly with cancer (malignancies, 21; congenital nephrotic syndrome, 1) between June 1989 and July 1991. The main complications in these patients were infection, occlusion of the catheters, and dislodging of needles. Infection occurred in 29% of the insertions, occlusion in 46%, and dislodging in 38%. Removal of this system was required in 29% of the insertions. This complication rate was higher than in previous reports, probably because of the younger patients in this study. The totally implantable catheter is very useful for patients who need long-term venous access. It is necessary to be cautious, especially in younger infants.

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An experimental study of infection accompanying malignant diseases was carried out by the Hokkaido Children's Research Group. The study composed combinations of Aztreonam/Piperacillin (A-group) and Tobramycin/Piperacillin (B-group) in a randomized trial of empiric therapy for febrile neutropenic cancer patients in the pediatric field. Of 121 febrile episodes included in the study between January 1990 and December 1990, 103 were evaluable. The two regimens were equally effective in episodes of documented infection. The response rates were 74.5% (41/55) and 83.3% (40/48) for the A-group and B-group, respectively. There were no differences between the two groups. Side effects were observed in 3 patients (3.2%) in the A-group, 4 (5.5%) in the B-group. However, they disappeared soon after the cessation of the treatment, or in spite of the continuation of the combination therapy. We conclude that the combination of Aztreonam/Piperacillin is a highly effective prophylactic regimen to treat infection in neutropenic patients after anticancer chemotherapy, and that Aztreonam should be considered to be a drug which can substitute for Tobramycin in the treatment of gram-negative infection in neutropenic patients in combination with other antibiotics for empiric therapy.

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A case of infantile genetic agranulocytosis (Kostmann type) was reported and the mechanism of impaired granulopoiesis was evaluated. Peripheral blood mononuclear cells obtained from this patient suppressed both autologous and allogeneic granulocyte-macrophage (GM) colony formation. GM-colony formation was augmented by the treatment of T-cell depletion from the patient's bone marrow mononuclear cells. Neither autologous nor allogeneic GM-colony formation were suppressed by patient's serum. These findings suggested that T-cells played an important role in the pathogenesis of Kostmann-type neutropenia of this patient.

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We report the heterogeneity in natural history of 3 infants with Langerhans cell histiocytosis (LCH). Case 1 was a 1-year and 6-month-old girl who was diagnosed unifocal eosinophilic granuloma. Her tumor was localized at right mandibula bone. We tried to remove the tumor tissues by curettage but we could not stop persistent exudation after operation, so she was treated with irradiation of total 8 gray. She was found to have hemiatrophy of the face of the irradiated site 5 years later. Cases 2 and 3 are both Letterer-Siwe disease. We did not treat Case 2 because of variable symptoms. He is now 5 years old and remains in complete remission. Case 3 received conventional chemotherapy including prednisolone, VCR and VBL. However, we doubt that this therapy could modify the true course of the disease itself. This study suggested the difficulties in categorizing the therapy of LCH. Further study is needed to establish the principle of the therapy of LCH.

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We evaluated the central venous catheter (CVC) -related complications in 37 children with various types of cancer who were receiving intensive chemotherapy and subsequent autografts with blood stem cells. The age of the patients ranged from 1 to 18 yrs, with a median of 8.5 yr. The CVC was used for the administration of drugs and blood sampling. The mean duration of catheter placement was 98 (3-260) days, and in 30 of 50 placements (60%) the procedure had achieved initial purpose without interruption. Infectious complications occurred in 124 occasions, of which 21 occasions had culture-proved bacteremia. In 5 occasions (10%) resistant to antibiotics therapy, CVC was removed. Occlusion of the CVC developed in 1.8 cases per placement. In 5 cases, the attempt to open the catheter with 10, 000 units of urokinase failed and the CVC was removed. The data support the notion that the use of CVC is a reliable procedure, associated with manageable morbidity in children receiving intensive chemotherapy.

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Productive abilities of granulocyte/macrophage-colony stimulating activity (GM-CSA) by monocytes were evaluated in children undergoing peripheral blood stem cell autograft. For this purpose, monocytes obtained from the blood before apheresis, collected cells in the apheresis bag and thawed grafts were cultured with or without M-CSF and then, supernatants were tested for GM-CSA in methylcellulose colony assay system with cord blood cells as a target population. The results indicate that monocytes were activated de novo at the time of harvesting and productive ability of GM-CSA had been retained during freeze-thaw procedure. There is a probability that hematopoietic growth factors produced by these activated monocytes play a part in the early recovery of hematopoiesis observed after peripheral blood stem cell autografts.

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A case of thrombocytopenic purpura after MMR (measles-mumps-rubella) vaccination is reported. A 2-year and 3-month-old boy developed purpura 3 weeks after the administration of MMR vaccine. A platelet count on the 26th postvaccination day was 13, 000/μl and the bone marrow showed increased megakaryocytes without platelets. His condition recovered spontaneously with the platelet count reaching 200, 000/μl on the 65th postvaccination day. Acute thrombocytopenic purpura has been a well-recognized complication of viral infections. It has also been observed after live vaccinations, e.g. for measles, but rarely reported after the administration of MMR vaccine. The present case suggests that thrombocytopenia was associated with MMR vaccination.

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Pearson syndrome is characterized by refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction which occurs during childhood. We reported a male infant suffering from severe anemia since his 6th day of life. He was treated with red blood cell transfusions frequently. Following the use of ubenimex from 6 months old, red blood cell transfusions were not required. He was normal growth and development. However, he developed severe dehydration and metabolic acidosis due to rotavirus infection at 23 months of age. Then dementia and motor disorders also developed. At 28 months of age, he died from Pseudomonas aeruginosa sepsis with severe metabolic acidosis and hypoglycemia. Postmortem specimens showed deletions of the mitochondrial DNA in each tissue. The deletions consisted of 4977bp from 8483 to np 13459. The etiology of anemia may be caused by heme synthetic disturbance because of high protoporphyrin level in his red blood cell and ringed sideroblast.

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This is a case report of severe ovarian hemorrhage in a patient with congenital afibrinogenemia. A diagnosis of congenital afibrinogenemia had been made prior to this bleeding episode. The patient was admitted due to an acute abdomen. The diagnosis of ovarian bleeding was promptly confirmed by blood tests, abdominal ultrasonography and magnetic resonance imaging. The patient was successfully treated with packed red cell, fibrinogen preparations and fresh frozen plasma without any complications. When a patient with congenital afibrinogenemia shows acute abdomen. one should consider the possibility of ovarian bleeding even though it is rare.

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A 15-year old girl with newly diagnosed ALL became febrile with neutropenia after induction chemotherapy. She was started on fluconazole empirically with antibiotics. Although, her fever disappeared when neutropenia was recovered, her serum CRP levels remained elevated. Abdominal CT showed multiple small lucencies throughout the liver, the spleen, and the left kidney. Multiple blood cultures and urine cultures were negative, but urinary fungus was detected by micros-copy, and Candida was isolated in her stools. The fluconazole dosage was increased, then, her CRP level returned to normal. Thereafter, her CRP levels were increased after each course of consolidation chemotherapy, and decreased when neutropenia was recovered. Ultrasound detected “the target lesion” earlier than CT in this patient. One year later, the lesions revealed the findings representing calcifications. She has been in complete remission as of now, receiving maintenance chemotherapy with fluconazole.

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Transient hyperammonemia is reported in two children with acute lymphocytic leukemia. They had no remarkable hepatic dysfunction in spite of being in a hyperammonemic state. Case 1, who had a second bone marrow relapse, had received amphotericin B (Amp-B) for fungal pneumonia. After two months of administration of Amp-B, he lost consciousness due to hyperammonemia, hypokalemia, and metabolic alkalosis. Forty hours later, ammonia, potassium, and blood gas analysis returned to normal, and he regained consciousness. In Case 2, hyperammonemia was present at the onset of his disease, before the initiation of chemotherapy. Ammonia was reduced spontaneously with induction of chemotherapy. Both Case 1 and 2 had no remarkable hepatic dysfunction during these episodes. There was no obvious cause that induced the hyperammonemia.

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A seven-year-old boy with diffuse T cell lymphoblastic lymphoma was treated with combination chemotherapy (predonisolone 60 mg/m², vincristine 1.5 mg/m², l-asparaginase 6, 000 U/m², pirarubicin 20 mg/m², cyclophosphamide 1, 200 mg/m²) and he was in a complete remission state after 16 weeks. However, during the consolidation phase 21 weeks post induction therapy the patient developed a fever and signs of acute respiratory distress. A presumptive clinical diagnosis of cytomegalovirus (CMV) pneumonia was made and treatment with ganciclovir 10 mg/kg and high dose methylprednisolone 20 mg/kg were initiated. Intravenous high-titer anti-CMV immunoglobulin was added after onset of pneumonia. The patient failed to improve and therapy with amphotericin-B and fluconazole were added. After 29 days, despite intensive anti-CMV and antifungal therapy the patient died. Autopsy findings revealed culture-positive CMV interstitial pneumonia and systemic aspergillus infection of the lungs, brain and kidneys. This case emphasizes the importance of careful monitoring for the first signs of opportunistic viral and fungal infection which can be fatal in the immunocompromised patient.

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