Mechanisms responsible for decision-making in hematopoietic development remains unknown. However, recent discoveries of erythroid-specific transcription factors that directly control lineage-specific transcription offer a means to solve this problem. The transcription factor GATA-1 is a fundamental regulator for erythroid development and belongs to a family of factors that bind to the consensus sequence WGATAR. The GATA-1 mRNA isoforms are transcribed tissue-specifically from two alternative promoters. The GATA motif was originally identified in cis-regulatory elements of globin and other erythroid-specific genes, but the range of genes controlled by GATA factors have expanded. Members of the GATA factor family share a conserved zinc finger DNA-binding domain, but the expression profile of each GATA factor is distinct. The second erythroid-transcription factor NF-E2, which is a heterodimetric protein complex comprised of products of p45 and the small maf family protooncogene (p18), is crucial for regulation of erythroid-specific gene expression and platelet formation. p45 NF-E2 mRNA isoforms are transcribed from two alternative promoters and encode the same protein. The first step towards an understanding of the.mechanisms for decision-making in hematopoietic development is to analyse the mechanisms of transcriptional control of these lineage-specific transcription factors themselves.

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Twenty-seven children with idiopathic thrombocytopenic purpura (ITP) were treated with high-dose intravenous immunoglobulin as the initial therapy. This therapy was effective in 25 of 27 patients (92.6%), with an increment in the platelet counts of more than 20, 000/μl. Their bleeding tendency was immediately controlled following the treatment. Adverse effects were limited to fever in 3 of 27 (11.1%) and febrile convulsion in 1 of 27 (3.7%). In spite of high-dose gammaglobulin therapy at the early onset, 8 of 27 patients (29.6%) proceeded to chronic type. Our results indicated that high-dose gammaglobulin therapy could not reduce the rate of proceeding to chronic type, compared to other agent such as corticosteroids. There was no difference in the clinical features at the diagnosis between the patients with acute and chronic ITP. The most effective therapy for childhood ITP must be determined thereafter, based on prospective and randomized studies.

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At present, the timing of collection of peripheral blood stem cells (PBSC) is determined from clinical observation based on the peripheral leukocyte and platelet counts. To assess the value of high fluorescence ratio (HFR) of reticulocytes as a guide for the collection of PBSC, this study was conducted since HFR is an early marker of hematopoietic recovery after bone marrow transplantation. Between 1991 and 1994, 64 stem cell apheresis were conducted for 21 patients with acute leukemia, malignant lymphoma, or solid tumors. After conditioning chemotherapy, G-CSF was used for every patient to increase leukocyte counts of 10, 000/μl or more. The number of mononuclear cells, CFU-GM and CD34⁺ cells in the collected blood were determined. Significant correlations were noted between HFR and the number of mononuclear cells collected (p<0.0001), between HFR and the number of CFU-GM (p<0.01), and between HFR and the number of CD34+cells (p<0.0001). HFR corresponding to young reticulocytes rose a few days prior to the outflow of stem cells into the peripheral blood in the course of bone marrow recovery. HFR serve as a useful guide for the collection of PBSC in preparing for apheresis.

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The Bone Marrow Transplantation Committee of the Society has conducted an annual registry of bone marrow transplantation in children in Japan since 1983. As of June 30, 1995, 2, 686 patients had received stem-cell transplantation and were registered from 120 institutions. Among them, autologous bone marrow transplantation was performed in 623 children (325 alive) and peripheral blood stem-cell transplantation was done in 509 children (321 alive), respectively. Allogeneic or syngeneic bone marrow transplantation were given to 1, 503 children, namely 461 cases of acute lymphoblastic leukemia (222 alive), 351 cases of acute myeloid leukemia (223 alive), 95 cases of adult-type chronic myelocytic leukemia (61 alive), 9 cases of juvenile-type chronic myelocytic leukemia (5 alive), 65 cases of non-Hodgkin's lymphoma (49 alive), 45 cases of malignant solid tumors (25 alive), 240 cases of severe aplastic anemia (211 alive), 42 cases of severe combined immune deficiency (20 alive), and 98 other cases (73 alive). The total number of transplanted cases has increased from 2, 166 to 2, 686 during the past one year. Unrelated bone marrow transplantation from “donor bank” donors was performed in 120 children, with an overall actuarial disease-free survival rate of 52.4±9.7%. Allogeneic cord blood stem-cell transplantation was done in 3 babies and allogeneic PBSCT was performed in 2 children. The details are reported in this paper.

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A ten-month-old boy was admitted to our hospital for pancytopenia. On admission, his white blood cell count was 2, 630/, μl, his hemoglobin level was 7.4g/dl, and his platelet count was 16, 000/μl. The bone marrow examination showed 7.4% blastic cells. However, one month after the admission, the pancytopenia was resolved and blastic cells in the bone marrow disappeared without specific treatment. One month after discharge, the patient was readmitted for a perianal abscess. On second admission, his white blood cell count was 6, 900/μl with 21% blastic cells. In the bone marrow, there were 26% blastic cells, which registered negative on the myeloperoxidase stain, but registered positive for CD13 and CD33. Chromosomal examination of blastic cells showed 47, XY, t (7 ; 12), + 19. Characteristically, 17% of the blastic cells were positive with platelet peroxidase. The diagnosis was MO according to the FAB classification. Complete remission was attained by chemotherapy with pirarubicin, vincristine and cytarabine. Spontaneous remission of pancytopenia before overt leukemia is unusual. Such a clinical course is similar to some cases of M7 leukemia. We suggest that some of M0 leukemia have similar findings of M7 leukemia.

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Using the recombinant human granulocyte colony stimulating factor (rhG-CSF), ecthyma gangrenosum in a neonate with congenital neutropenia was successfully treated. On day 4 of life, the male baby had perianal deep erythema, which rapidly developed to necrotic demarcated ulcerations caused by Pseudomonas aeruginosa. He had severe neutropenia (200/, μl), and was treated with rhG-CSF in combination with intensive antibiotics. After the administration of rhG-CSF, the number of neutrophils was elevated and the perianal ecthyma resolved. Bone marrow (under the treatment of rhG-CSF) revealed hypoplasia of neutrophils and their precursors. Antineutrophil antibodies were not detected in his serum. The maintenance therapy with rhG-CSF (10→25→40μg/day) was performed and the number of neutrophils was maintained 300-500/μl. Daily administration of rhG-CSF was altered to intermittent administration, but he has been free from severe infectious diseases. His mother also had had moderate neutropenia (200-500/μl) for a long time without severe infections. The congenital neutropenia in the patient is probably classified as familial benign chronic neutropenia, although he had severe infections during the newborn period. rhG-CSF was also effective for prophylaxis of severe infections in this case.

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n one-year-3-month-old boy was admitted to our hospital because of anemia, thrombocytopenia and subcutaneous bleeding. He was subsequently diagnosed as having acute mixed lineage leukemia (MLL) by surface marker analysis. The chromosome abnormality of leukemic cells was 47, XY, +21, 12p+. The complete remission was achieved by intensive chemotherapy. We performed the peripheral blood stem cell autotransplantation (PBSCT) when he was 2 years and 11 months old. Seven months after the PBSCT, chromosomal analysis of his bone marrow cells showed 47, XY, +21, 12p+. This abnormality, which was the same one revealed at the time of first admission to our hospital, was found only in one cell out of 20 examined cells. Then we began to treat him with the adjuvant therapy of 6-mercaptopurine and prednisolone for about 7 months. We think that PBSCT is safe and effective therapy for MLL in childhood ; however, adjuvant therapy is necessary for cases showing minimal residual disease after receiving PBSCT.

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We describe herein the case of an 8-year-old girl with CMMoL. Previously, she was treated with etoposide and prednisolone, but she did not improve. Thus, we tried to administrate cytarabine ocfosfate (SPAC) as a treatment. Three courses of oral administration of SPAC (50 mg/day) for 2 weeks was given, and 100 mg/day for 2 weeks was repeated for two courses. During these treatments, thrombocytopenia improved without any adverse effects. So, she has been able to go to school and this treatment has resulted in an apparent improvement of QOL. However, there was no improvement on bone marrow and the treatment was discontinued for 7 months. She died of acute respiratory failure 6 months after the termination of treatment. We consider that the QOL of a patient is very important, especially in diseases with a poor prognosis. We recommend that SPAC is an effective treatment for MDS patients who can not receive bone marrow transplantation.

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A 13-year-old girl with hemoglobin (Hb) Hamadan was found in routine examination for adult disease in childhood because of her low Hb A_1c level. Abnormal Hb was detected using HPLC and cellulose acetate membrane electrophoresis. In further analysis of abnormal Hb, the 56th amino acid of the β-chain was found to be arginine instead of glycine. Her elder brother also had the same abnormal hemoglobinopathy. Although hemoglobin Hamadan is one of the asymptomatic hemoglobinopathies, the incidence of this disease has been increasing recently. Recognition and frequent employment of Hb A_1c measurement as a useful tool for patient care of diabetes mellitus is thought to be the reason for this increase.

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We describe herein siblings with neonatal allo-immune thrombocytopenic purpura (NATP) due to fetomaternal human platelet antigen (HPA) -3a incompatibility. This is the third case report in Japan. The mother was healthy and had no history of bleeding tendency. Both infants were born vaginally after an uneventful term pregnancy. In both cases, petechial hemorrhages were noted immediately after delivery. The platelet count was 2.0 × 10⁴/μl in the first and 1.0 × 10⁴/μl in the second infant, respectively. The second infant developed intracranial hemorrhages. The mother's serum reacted specifically with platelets from her infants and husband, and was found to contain anti-HPA3a and anti-HLA platelet-specific alloantibodies. In both, the platelet count exceeded 10.0 × 10⁴/μl 4 weeks after the high-dose intravenous administration of gammaglobulin. The platelet count transiently increased after transfusion with random-donor platelets in the second infant. Correct diagnosis and early treatment of NATP is desirable in order to reduce the mortality and neurological sequelae secondary to intracranial hemorrhage in the neonatal period.

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