The number of pediatric HIV-infected persons and AIDS patients is showing a tendency to increase worldwide. Approximately 90% these cases are due to mother-to-infant transmission. Three routes of infection are recognized : 1) intrauterine infection, 2) intrapartum infection during delivery and 3) infection via breast feeding. Accordingly, prophylactic strategies include preventative administration of AZT (zidovudine) to both the mother and child, planned cesarean section, and prohibition of breastfeeding. Pediatric AIDS is broadly divided into a rapidly progressive type (20%) and a slowly progressive type (80%), and to prevent the onset of AIDS early diagnosis within 6 months of birth using the PCR method is indicated. After the diagnosis is established, HIV markers and CD4 counts are periodically monitored, and early administration of ST compounds to prevent Pneumocystis carinii pneumonia is intiated. For the infected mother, counseling is mandatory according to the period, and in addition it is essential that after delivery a social support system be established for the patient and family.

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Lymphocyte subpopulations and the distribution in the spleen and the lymph nodes in children who had hematopoietic malignancy or solid tumor, were investigated immunohistologically by the PAP method and by flow cytometry. Monoclonal antibodies used in this analysis were Leu4 (CD3), Leu3a (CD4), Leu2a (CD8), Leu 16 (CD20), IL-2 receptor (CD25) and TCRγ/δ. Eleven cases of hematopoietic malignancies (acute myelocytic leukemia, acute lymphocytic leukemia, malignant lymphoma), histiocytosis, neuroblastoma, and brain tumor were studied. Accessory spleen and hypersplenism were investigated as a control study. Immunohistologically, the lymph node and the spleen of the patients with malignant neoplasms showed that T and B lymphocytes decreased in number throughout, but their distribution was not unusual. The CD4/CD8 ratio was normal or slightly low. IL-2 receptor-positive cells decreased in number, but the CD25⁺CD3⁺/CD3⁺ ratio was higher than the usual level. The T lymphocyte-activating function seemed to be preserved in the patients with malignant neoplasms. These results suggest the possibility that immuno-activating therapy, for example cytokine therapy, may improve cellular immunity in the pediatric patient bearing malignancy. Bone marrow transplantation (BMT) decreases the CD25⁺CD3⁺/CD3⁺ ratio and lymphocyte activation, as compared with other chemotherapy. Therefore, it may be necessary that the patients undergoing BMT should be treated with more effective immuno-activating therapy.

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Fifteen children, 5 boys and 10 girls, with hemophagocytic syndrome (HPS) were treated between 1982 and 1994. They ranged in age from 8 months to 10 years. None of them had an affected siblings with a similar disorder. Two of the 15 patients received no therapeutic drug during the clinical course. Two received oral prednisolone (Pred). Eleven were treated with antineoplastic drugs. Eight received etoposide (VP-16) and Pred, 1 VP-16 and cytosine arabinoside (CA), 1 ACOP [adriamycin (ADR), vincristine (VCR), cyclophosphamide (CY) and Pred] and 1 CHOP [CY, ADR, VCR and Pred]. Complete remission (CR) was achieved in 9 patients. Ten are now alive and free of disease 9+ to 144 + months from the onset of disease. Five of the 15 patients died with a median survival of 26 days. Among several clinical findings, loss of consciousness and a high level of serum glutamic oxaloacetic transaminase and lactate dehydrogenase were closely associated with a poor prognosis. Serum levels of interferon gamma (IFN-γ) and soluble interleukin 2 receptor (sIL-2R) were assayed in 7 children during the acute phase of HPS. Serum IFN-γ and sIL-2R levels were elevated significantly with a median of 9.6 U/ml (range 0.5-30<U/ml) and 6, 184 U/ml (range 2, 476-12, 000<U/ml). Six of 9 patients treated with VP-16 achieved CR, irrespective hypercytokinemia. VP-16 is effective in HPS, so we should use it cautiously, considering the leukemogenesis. Further investigations of staging system and protocol studies should improve the outcome.

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Circulating mononuclear cells stained with CD34 monoclonal antibody were analyzed using a fluorescence-activated cell sorter (FACS) in 10 cases of aplastic anemia. After immunosuppressive treatment, CD34-positive cells increased in 5 of 6 cases. CD34-positive cells also increased after administration of granulocyte colony-stimulating factor (G-CSF) in 5 of 7 cases. The increase of CD34-positive cells was correlated with the immunosuppressive response and G-CSF therapy. Compared with other hematological diseases and solid tumor, the increase of CD34-positive cells in the cases of aplastic anemia was delayed after administration of G-CSF.

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Thrombomodulin (TM) is a vascular endothelial cell membrane glycoprotein which complexes with thrombin to accelerate protein C activation. Recently, its soluble forms have also been demonstrated to be present in plasma and urine. These soluble forms of TM are expected to be a specific parameter of endothelial cell injury. In this study, plasma and urine levels of TM were investigated in neonates, infants and children. There was a good correlation between plasma TM and urinary TM levels in healthy children. The level of soluble TM in neonates and infants is higher than that in adults, and it decreases to adult levels in children.

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A 13-year-old boy diagnosed as having Philadelphia chromosome-positive chronic myelogeneous leukemia received interferon-alpha therapy and a cytogenetical minor response was obtained. Subsequently, bone marrow from his HLA-identical MLC-negative sister was transplanted. As a conditioning regimen, little BU/CY was applied instead of a total body irradiation-containing regimen. The doses of each drug were calculated on the basis of ideal body weight. Significant regimen-related toxicity was not observed. Monitoring of minimal residual disease by RT-PCR and endocrinological evaluation were performed for 2 years following BMT and no chimera mRNA from BCR-ABL fusion gene were detected. GH secretion stimulated by L-dopa and arginine showed normal response and the boy's height increased at a normal rate. However, LH-RH test showed hypersecretion of LH and FSH whereas serum testosterone and IGF-1 levels were appropriate for his age. Thus, normal development of pubertal process was observed during the next 2 years. These data indicated the presence of mild hypergonadtropic hypogonadism. In addition, TRH test showed hypersecretion of TSH and prolactin, although serum T3, T4 and TSH were all within the normal range, which suggested latent hypothyroidism. This case suggested that : 1) preconditioning by little BU/CY is safe and effective, when cyotogenetical minor response is obtained by IFN-alpha, 2) endocrine organ dysfunction may be caused by this conditioning regimen.

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Hereditary elliptocytosis (HE) is a heterogenous group of inherited disorders characterized by the presence of elliptical red blood cells (RBC) on peripheral blood smears and rarely leads to hemolysis. Recently, HE has been revealed to result from various membranous skeletal protein defects and some of them have been characterized by chromosomal and/or DNA sequence abnormalities. The patient was a 7-year-old boy who was admitted as PSAGN (poststreptococcal acute glomerulonephritis) complaining of macroscopic hematuria and facial edema. During evaluation of his peripheral blood smear, HE was found incidenally. SDS-PAGE revealed a partial deficiency of membrane protein band 4.1. We performed some drug-induced hemolysis tests on the patient's RBC. From the results of this hemolysis tests, it was suggested that his RBC have higher sensitivity to ampicillin than normal RBC. Although he showed no obvious hemolysis clinically, some membrane instability of his RBC was demonstrated by the hemolysis test.

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The patient was a 14-year-old girl who presented with hematuria due to disseminated intravascular coagulation (DIC), and subsequently she was diagnosed with acute promyelocytic leukemia (APL) by bone marrow aspiration. The bone marrow aspiration revealed 81.8% atypical promyelocytes, many of which contained multiple Auer rods and prominent coarse granules. Chromosomal analysis of bone marrow aspirate showed a 46, XX/46, XX, 15q⁺, -7, + i (17q^-) (29 : 4). She was treated for 77 days with oral all-trans retinoic acid (ATRA 45 mg/m²/day). On the second day after the therapy started, her bleeding tendency was improved significantly and white blood cell counts were gradually elevated, leukocytes were differentiated to myelocytes and metamyelocytes from 2-wk to 4-wk. However, at week 5, leukocyte counts were decreased and the leukocytes no longer differentiated to mature granulocytes. On day 53, ATRA therapy combined with granulocyte colony-stimulating factor (G-CSF 100, μg/m²/day s. c.) was tried, and the leukocyte counts elevated (maximum 9, 100/μl) and leukocytes were differentiated to mature granulocytes. On day 63, she entered complete remission in the bone marrow. On gene analysis, RAR-ca rearrangement disappeared. As a side effect, headache, nausea and thirst sensation appeared but resolved within 3 days. ATRA therapy was the most effective treatment for APL associated with DIC and may be useful as a remission induction therapy without bone marrow suppression. For those who respond poorly to ATRA therapy alone, ATRA and G-CSF combined therapy appears to be quite useful.

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Diffuse alveolar hemorrhage (DAH) is one of the life-threatening complications after bone marrow transplantation (BMT). A 4-year-old boy with acute lymphocytic leukemia received BMT from an unrelated bone marrow donor. The preconditioning regimen consisted of total body irradiation, melphalan and thiotepa. After BMT, severe mucositis was seen. Recovery of white blood cells was seen on day 12 after BMT. On day 22, he developed severe graft-versus-host disease (GVHD) with rash on general skin, bloody diarrhea and fever accompaning cytomegalovirus enteritis. By treatment with steroids, FK506 and ganciclovir, these symptoms seemed to improve. On day 33, however, he showed severe dyspnea. On the basis of bloody sputum and diffuse consolidation of the chest X-ray, diagnosis of DAH was made. Therapies such as steroid pulse and surfactant were ineffective, and he died at day 42. Intensive prophylaxis of GVHD and reduction of mucosal toxicity of conditioning regimen may be needed to prevent DAH in allogeneic BMT.

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We report two patients who developed chronic progressive radiation myelopathy (CPRM). Patient 1 was a 16-year-old boy with group IV rhabdomyosarcoma of cervical soft tissue. He underwent partial excision of the tumor and received systemic and intrathecal chemotherapy and 44 Gy of local radiotherapy (C4 through Th3). These therapies were followed by high-dose chemotherapy including thio-TEPA and busulfan with autologous bone marrow rescue. One year after the completion of the therapies, he developed CPRM. Patient 2 was a 15-year-old girl with acute lymphoblastic leukemia on the 3rd complete remission. She received 18 Gy of irradiation to whole brain during the 1st remission and another 18 Gy to whole brain and 9 Gy to spinal cord after her 1st CNS relapse. After successful reinduction therapy for the 2nd relapse in CNS and bone marrow, she underwent an allogeneic bone marrow transplantation (BMT). The preconditioning regimen consisted of 12 Gy total body irradiation, thio-TEPA and cyclophosphamide. Seven months after BMT, she developed CPRM at CO-C1 level, which was included in the area of whole-brain irradiation. In both patients, MR images showed a swelling of the cervical cord and ring-like images by gadolinium enhancement. Their neurological disability transiently responded to the administration of corticosteroid, but they developed progressive quadriplegia. Although it is reported that a dose of 45-50 Gy may be safe, these cases suggest that administration of high-dose chemotherapy combined with intrathecal chemotherapy and radiotherapy to the cord might increase the risk of developing CPRM.

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