To analyze the complex mechanism of growth of leukemic cells In vivo, the immunodeficient (SCID) mouse model will provide a powerful new approach to characterize, human leukemia. Most human leukemic cells grow by interacting with stromal or accessory cells In vivo and in vitro. Cytokines produced by these supporting cells or by the leukemic cells stimulate the proliferation of leukemia in paracrine or autocrine fashion, respectively. The contact of leukemic cells to extracellular matrix is one of the main pathways to disseminate to peripheral organs. Normal hematopoietic cells engrafted in SCID mice grow and differentiate in BM by the support of several growth factors. The ALL cell lines and cells from patients grow and disseminate in the SCID organs, and the growth pattern of leukemic cells in SCID mice correlates with the course of disease in each patient. However, most AML cells grow in SCID organs with the presence of several growth factors. The proliferation of leukemic cells in SCID mice can be prevented by immunotoxins and anticancer drugs, suggesting that these drugs will be effective to treat the patients with refractory leukemia. The SCID mouse model will provide useful information to analyze the mechanism of growth of leukemic cells In vivo.

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Biphenotype leukemia has been considered to be one of the therapy-resistant leukemia that express ectoenzymes on their surface. We investigated the activity of neutral endopeptidase (CD 10) and aminopeptidase N (CD 13 : APN) in acute lymphoblastic leukemia (ALL), biphenotype ALL and acute non-lymphoblastic leukemia (ANLL) cell lines. Biphenotype cell had both activities that mean to have ALL and ANLL character. The enzyme inhibitors could inhibit these activities in a dose dependent manner. Especially, ubenimex, a specific inhibitor of APN, inhibited APN activity and cell growth under the concentration of clinical use. These results suggest that ubenimex has some clinical benefits on CD13-positive ALL-like ANLL.

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Proportions of CD 10⁺ cells in bone marrow cells were analyzed in 18 children with leukemia (13 cases of ALL, 4 of AML and 1 of CML) and 1 child with neuroblastoma. Higher proportions of CD 10⁺ cells in bone marrow were observed in patients less than 18 months after cessation of maintenance therapy of leukemia than after induction or consolidation therapy and during maintenance therapy. The increment of CD 10⁺ cells was observed in the bone marrow of all cases after cessation (or completion) of maintenance therapy. Therefore, it is important to distinguish CD 10⁺ cells from the relapsed leukemia cells, especially in common ALL. A significant positive correlation between the proportions of CD 10⁺ cells and CD 19⁺ cells and a negative correlation between CD 10⁺ cells and CD2⁺ cells were observed in bone marrow cells. These data suggest that increment of CD 10⁺ cells in the bone marrow might reflect a recovery state of the bone marrow from the suppression by chemotherapy.

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We herein describe 5 children (1 boy, 4 girls) who were diagnosed with idiopathic pulmonary hemosiderosis (IPH) during these 10 years. The age of onset ranged from 11 months to 3 years. The first symptoms of all children were fever and anemia, however one child complained of hemoptysis. With the exception of one child, there were respiratory symptoms at the onset of IPH in all cases. Blood transfusions were needed in 3 children, all of whom died within 6 months after onset, and 2 others are alive. Four children had various perinatal abnormalities, and 3 of them received mechanical ventilation. Barotrauma due to mechanical ventilation may cause the alveolar epithelial alterations. We suggest that in our cases, these alterations may be one of the pathogenic mechanisms of IPH.

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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, 1994, 2, 166 patients had received stem-cell transplantation and were registered from 100 institutions. Among them, autologous bone marrow transplantation was performed in 543 children (292 alive) and peripheral blood stem-cell transplantation was done in 357 children (224 alive). Allogeneic or syngeneic bone marrow transplantation were given to 1, 229children : 375 cases of acute lymphoblastic leukemia (190 alive), 302 cases of acute myeloid leukemia (188 alive), 79 cases of adult-type chronic myelocytic leukemia (49 alive), 7 cases of juvenile-type chronic myelocytic leukemia (3 alive), 47 cases of non-Hodgkin's lymphoma (34 alive), 37 cases of malignant solid tumors (17 alive), 215 cases of severe aplastic anemia (188 alive), 39 cases of severe combined immune deficiency (19 alive), and 128 other cases (81 alive). The total number of transplanted cases has increased from 1, 735 to 2, 166 during the past one year. Unrelated bone marrow transplantation from “donor bank” donors was performed in 54 children, with an overall actuarial disease-free survival rate of 48.1 ± 15.8%. The details are reported in this paper.

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We experienced a 12-year-old boy with T-cell lymphoma positive for CD45R0 which developed as midline granuloma syndrome after remittent fever of about 3 years. Differential diagnosis was difficult in this patient, and the onset followed a specific course. Moreover, the condition was complicated with HPS resistant to various treatments, and the prognosis was unfavorable.

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We report a case of Ph¹-positive myelodysplastic syndrome (MDS) which was supposed to evolve into aplastic anemia. In February 1986, a 6-year-old girl was referred to our hospital because of a bleeding tendency. Peripheral blood pancytopenia and hypercellular bone marrow with myelodysplastic changes indicated a diagnosis of MDS. Cytogenetic study of bone marrow cells revealed t (9; 22) in one of 7 metaphasic cells. Four years after onset, progressive pancytopenia compatible to severe type of aplastic anemia and hypoplastic bone marrow were observed. At that time no myelodysplastic change or Ph¹ chromosome could be detected. She underwent bone marrow transplantation (BMT) from an HLA-matched sibling and has been in continuous complete remission 30 months after the BMT. This may be the first report of Phi-positive childhood MDS which developed into aplastic anemia.

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We reported an 11-year-old boy with chronic myelogenous leukemia having t (2; 9) (p13; q34) who was admitted to our hospital with complaint of short stature. Breakpoint cluster region (BCR) rearrangement was shown to be negative by Southern blot hybridization, but chimeric BCR-ABL mRNA was detected. He achieved complete remission by α-interferon and hydroxyurea and allogeneic bone marrow transplantation successfully performed.

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Here we report a case of myelo-dysplastic syndrome (MDS) with monosomy 7, which occured after chemotherapy. The patient was a 5-year-old girl who had undergone surgery for ependymoblastoma at the age of 1 year and 5 months followed by chemotherapy for 2 years. However, 36 months after the start of chemotherapy, pancytopenia developed and blast cells were found in the peripheral blood. Bone marrow aspirate revealed hypocellularity with about 30% blast cells lacking peroxidase stain. Chromosome analysis of the blast cells revealed them to be 45, XX, -7. Therefore, MDS with monosomy 7 developed after chemotherapy. Treatment with prednisolone and a low-dose cytosine arabinoside regimen was started. The blast cells were decreased in peripheral blood. At that time Granulocyte colony-stimulating factor was administered to her, subsequently the leukocyte count increased, accompanied by a more rapid increase of blasts. She died because of sepsis.

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A 7-year-old boy suffering from Bloom's syndrome (BS) developed a submucosal tumor in the duodenum. Following a subtotal resection, the diagnosis was made as non-Hodgkin's lymphoma (diffuse mixed type and B-cell type). The patient was in stage IV with bone marrow involvement. The patient was treated according to the B-8801 protocol of TCCSG (Tokyo Children's Cancer Study Group). A reduction of anticancer agents to half of the scheduled doses was required due to hematological toxicity and severe mucositis. He has been disease-free for a year after the completion of a 12-month chemotherapy protocol. Our case requires careful follow-up study including late adverse effects and for a second malignancy. Previous reports from Japan revealed that 8 of 16 patients with BS developed malignant neoplasms.

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We report a case of non-lymphocytic leukemia which was considered to be related to etoposide containing chemotherapy for relapsed acute lymphoblastic leukemia (ALL). A 10-year-old boy was admitted in our department in April 1988 because of bone pain and was diagnosed as having common ALL with normal karyotype. He was treated by our standard risk ALL protocol (UH-8201) until December 1990, but he had bone marrow and testicular relapse 2 months after off-therapy and was treated by the PVDA and BFM rez87 regimen until December 1991. Blast cells appeared in peripheral blood in July 1992. Blast cells in that time changed to monocytoid appearance with t (9; 11) (p22; q23) and the rearrangement of MLL gene. Therefore this case was considered secondary leukemia related to etoposide used in a chemotherapy regimen. The total cumulative dose of etoposide was 1, 060 mg/m².

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