The most significant recent advances in bone marrow transplantation in children include the increasing number of diseases which can be treated successfully by this therapy, methods of increasing the number of available donors and the prevention of cytomegalovirus (CMV) infections. Matched allogeneic marrow transplantation is now established therapy for selected patients with leukemia, myelodysplastic syndromes, aplastic anemia, immunodeficiency syndromes and osteopetrosis. Recently, marrow transplantation has been successfully extended to the treatment of hemoglobinopathies, particularly thalassemia, and certain metabolic storage disorders such as Hurler's syndrome and metachromatic leukodystrophy. The development of effective marrow T-cell depletion techniques and unrelated donor registries offer the promise of increasing the number of patients who can benefit from this therapy by enabling mismatched transplantation. Obstacles that have to be overcome include the increased risk of graft failure and leukemic relapse associated with T-cell depletion, and graftversus-host disease characterizing mismatched transplantation. Finally a major advance in preventing CMV pneumonia, until recently the major cause of death following bone marrow transplantation, has been use of CMV-negative blood products when the patient and marrow donor are CMV negative.

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The inherited marrow failure syndromes are a heterogeneous group, with all types of genetic patterns, and the entire gamut of symptoms and physical findings. The only condition which can be diagnosed with certainty is FA, because of the chromosome breakage ; even this diagnosis requires thinking of it first. Many of the patients with these syndromes are not properly diagnosed initially; since treatment depends on diagnosis, it is important that these conditions be considered for every patient with single or pancytopenia. Hematopoietic cultures may be useful for defining the diagnosis or determining the prognosis. Many of these syndromes can be detected in utero in subsequent pregnancies, and thus there is an additional reason for early diagnosis of the propositus. Since at least heterozygotes for some of these conditions may be common (e.g. FA 1/200), it is reasonable to suggest that aplastic anemia genes may be sufficiently prevalent to explain even “acquired” aplastic anemia.

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We have analyzed the alteration of hexokinase (Hx), pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6PD), malate dehydrogenase (MDH) and δ-aminolevulinate systhetase (δ-ALA s) activities of erythrocytes, bone marrow and spleen cells during erythropoietic stimulation. The studies in vivo were carried out on female Wistar rats that received an intraperitoneal injection of acetylphenylhydrazine (APH) at a dose of 60 mg/kg body weight. Peripheral blood and bone marrow cells were collected daily from the beginning to the recovery stage of anemia. Increasing of erythrocyte Hx and G6PD activities were observed from 4 to 6 days after APH injection. Both Hx and G6PD activities of bone marrow cells decreased at 3 days after the injection and recovered to normal activities at 6 days after the injection. We have also examined the enzyme activities of suspended spleen or bone marrow cells after stimulation with 1 U/ml erythropoietin (Epo) in vitro. PK and G6PD activities of bone marrow cells were stimulated at 2-4 hours after exposure to Epp. The increase of MDH and δ-ALA s activities were detected after 24 hours of incubation with Epo. These data suggest that the alteration of glycolytic enzyme activities were induced earlier than that of MDH or δ-ALA s in rat bone marrow and spleen cells under the erythropoietic stimulation.

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It has been well recognized that anemic condition is prevalent in premature infants. It is a purpose of this study to find if the anemia of prematurity is related with the low or lack of erythropoietin production. Serum specimens were harvested from premature infants with gestational age between 30 weeks 5 days and 40 weeks 1 day and birth weight ranging from 1, 600 to 1, 900 g. Specimens were obtained from babies without any clinical abnormality except low birth weight, with age between one to 106 days. Erythropoietin activity was studied utilizing radioimmunoassay method. Erythropoietin was detected since the first day of life and increased after three weeks, when the values reached almost the same level as compared to those of healthy adults. The hemoglobin concentrations in premature infants were decreased rapidly after birth and reached the lowest level approximately eight weeks later. The relatioship between hemoglobin concentration and erythropoietin level showed negative correlation. However, elevated erythropoietin activity still remained within the normal range of those shown in the adults except two cases. Also, negative correlation between hematocrit and erythropoietin activity was observed. All subjects were classified into two groups on the basis of the lowest hemoglobin concentration during the course, i.e. below 10 g/dl as group A and 10 g/dl or above than that as group B concomitantly. The erythropoietin activity in group A showed much higher than that of group B. These findings suggest that the premature infant has the ability to produce erythropoietin. However, producibility of erythropoietin responding to the anemia seems to be lower as compared to other types of anemia.

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I examined platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) on healthy children. Platelet count increased during the first week following the birth of a baby, was maximal at 2-3 weeks old and remained at a high level from 1 to 6 months of age. Thereafter, platelet count was decreasing with age. MPV was 8.03 μ³, 8.31 μ³, 8.08 μ³, 7.62 μ³, 7.82μ³, 8.10 μ³, 8.53 μ³ and 8.62 μ³, in normal babies with full term, in premature babies, in normal individuals at the age of 1-6 months, 1/2-2 years, 2-6 years, 6-12 years, 12-16 years and in normal adults, respectively. MPV was larger at neonatal period and 1-6 months old than those at 6 months-2 years old and smallest at 6 months-2 years old and gradually increasing with age. Therefore there was an inverse relationship between the number of platelets and their MPV. PDW was wide, with number of platelets at 100-200 × 10³/μl. Also PDW at 1-6 months old was significantly wider than those at any other ages. No significance was seen regarding PDW over 200 × 10³/μl of platelets for children after the age of 6 months. Its mean PDW was 16.17-16.31%.

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An 11-year-old girl presented with a history of right cheek swelling. Histological findings of specimen excised from a tumor in the right maxillary sinus showed Burkitt's lymphoma. Computed tomography revealed her maxillary and ethmoidal sinuses in the right side to be filled with tumor, and a part of zygomatic bone to be destructed by invasion. An analysis of the surface marker of tumor cells revealed Ia⁺, B1⁺ B2^-, CALLA- and SIgM⁺ (70%), indicating that cells of this tumor classified into B cell type. A chromosomal analysis of tumor cells showed 11q+, dup (12), lacking t (8 ; 14), t (2 ; 8), nor t (8 ; 22). She received systemic chemotherapy including high-dose (HD) CPM and HD MTX, attained a complete remission and received periodic consolidation therapies together with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). She underwent no radiation therapy. She has presently remained in complete remission for abont 3 years, and is now followed as therapy-free. Further study is needed to clarify Burkitt's lymphoma without nonrandom translocation.

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An infantile case of microgranular variant of acute promyelocytic leukemia (APL) is reported. The patient was a 1-year-old girl who suffered from disseminated intravascular coagulation and chromosomal abnormality of 15 ; 17 translocation. WBC count at diagnosis was 180, 000/μl. Blasts appeared not only in bone marrow but also in urine and CSF. Distinctive features of the blasts were bilobed nuclei, “dust-like” azurophilic inclusions and no faggots in the cytoplasmas. Shs was in remission after three courses of chemotherapy regimens. After ten months from diagnosis she died of fulminant hepatitis of type B. Previously reported cases with APL in childhood including our case were also reviewed.

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We reported a case of tuberous sclerosis with acute lymphocytic leukemia. A 9-year-old girl with tuberous sclerosis consulted her local pediatrician because of fever and general fatigue. The results of the examination of peripheral blood and bone marrow led to the diagnosis of acute lymphocytic leukemia, and she was admitted to our hospital. The blasts were positive for PAS stain, and negative for peroxidase stain. Surface marker analysis revealed that the blasts were positive for CD9, CD 10, CD 19, CD 20 and HLA-DR. She was treated with chemotherapy, and bone marrow remission was attained. Several cases of neurofibromatosis with leukemia are reported, but it is uncommon that tuberous sclerosis is complicated with leukemia.

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A 7-year-old girl was admitted due to cough, fever, chest pain and facial edema. Her left lung was collapsed by the remarkable pleural effusion. The anterior mediastinal tumor shadow became clear radiographically after the drainage of the pleural fluid, which was found to contain numerous lymphoblasts with positivity of monoclonal antibodies such as CD 1, 2, 3, 4, 5, 7, 8, 38 and 57. With the diagnosis of the mediastinal T-cell non-Hodgkin's lymphoma, she was treated with chemotherapy resulting in no remarkable shrinkage of her anterior mediastinal tumor and she died of infections. With a marked contrast, five patients with CD57-T-cell malignancy treated during this period had good responses by chemotherapy similar to the regimen prepared for the CD57+ patient. Natural killer cell-associated surface antigen (NK-At) -positive non-Hodgkin's lymphoma should be distinguished as a biologic subtype from the NK-At-negative T-cell non-Hodgkin's lymphoma because of its poor response to chemotherapy. Especially in this subtype, CD57+ cases are more frequently seen in young females with the anterior mediastinal tumor. No similar case has yet been reported in Japan. A special strategy should be considered for more effective treatment on this tumor.

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An 11-year-old boy with severe aplastic anemia was treated by allogeneic bone marrow transplantation (BMT). The transplant donor was his 3-year-old sister, who was HLA-identical, MLC-negative, and ABO mismatched. Beginning the day after BMT, the patient received an intravenous injection of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) at a dosage of 250μg/m²/day for 25 consecutive days. The increase in granulocytes started on day 15 and exceeded 500/cmm by day 19. A platelet count greater than 105 was obtained on day 29. We compared the recovery of granulocytes and platelets in the patient with those in two patients with severe aplastic anemia, who were treated with the same conditioning regimen and received recombinant human granulocyte colony-stimulating factor (rhG-CSF) after BMT. Although recovery of granulocytes by rhGM-CSF administration was similar to that by rhG-CSF, rhGM-CSF seemed to more intensively stimulate platelets recovery than rhG-CSF. He had antibiotics-resistant high fever until the administration of rhGM-CSF was discontinued, suggesting rhGM-CSF itself might be a cause of high fever. No other side effects were observed. These results suggest that rhGM-CSF may be beneficical to hemopoietic recovery after BMT in pediatric patients.

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A 6-month-old infant with antoimmune pancytopenia who presented with gingiva bleeding was treated by combination therapy with prednisolone and recombinant human granulocyte colony-stimulating factor (rhG-CSF). Initially, intravenous high dose immunoglobulin and oral prednisolone were found to be of no benefit. Subsequently, the patient received combined prednisolone and rhG-CSF (25-100 μg/m²/day, intravenously or subcutaneously) for 3 months, which were effective but transient. Thereafter, similar combination therapy including rhG-CSF (50-200 μg/m²/day, subcutaneously, 6 months) was shown to be very effective. The hemogram has dramatically improved and the patient is in complete remission for more than 9 months after discontinuation of the therapy. No adverse effect of rhG-CSF was observed.

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We report an 8-year-old girl case with B-cell ALL (FAB L3) presenting exophthalmus and meningitis-like symptoms. There was a histological difference between cells in cerebrospinal fluid (CSF) and bone marrow (BM) cells. Repeated cytological examination of CSF could define the disease. We diagnoted her B-cell ALL by surface marker study. CT scan revealed a tumor in paranasal cavity, so we considered this case a leukemic stage of Burkitt lymphoma.

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Three children with refractory acute lymphocytic leukemia received therapy with vincristine/ prednisolone/ l-asparaginase and recombinant human granulocyte colony-stimulating factor (G-CSF). One patient achieved complete remission and other patients achieved incomplete remission (5% or less blasts in bone marrow with abnormal peripheral and differential counts except a granulocyte count). Remission durations were short with a median of 40 days; the median survival was 137 days. One patient died of pulmonary fungal infection, but other deaths were due to relapsed leukemia. Side effects included infections, hypoalbuminemia, hypofibrinogenemia and hyperglycemia. In conclusion, the combination of vincristine/ prednisolone/ intensive l-asparaginase and recombinant human G-CSF had significant activity in children with refractory acute lymphocytic leukemia but the duration of remission was short. The addition of recombinant human hemopoietic growth factors to the intensive chemotherapy and the use of the combination regimen as part of front-line maintenance intensification therapy may further improve the prognosis in these patients.

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We reported a 13-year-old boy with acute myeloblastic leukemia (AML) having specific chromosomal translocation t (6 ; 9) (p23 ; q34) and marked hypophosphatemia in the terminal stage. He was admitted for fever and hip joint pain. His white blood cell showed to be 35, 300/μl with 92.5 % blasts. His bone marrow showed to be 46, 300/μl with 36.5% blasts which were classifiable as M1 according to the French-American-British (FAB) classification. A chromosomal analysis of bone marrow leukemic cell revealed t (6;9) (p23 ; q34). In spite of various intensive chemotherapy, he did not attain complete remission, and he died after the 5 months since the initiation of induction therapy. Peripheral basophilia appeared during the course of this first treatment, and a marked decrease in serum and urinary phosphates occurred in the terminal stage. We discussed the clinical features of this translocation and hypophosphatemia observed during the course of this patient.

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A 6-year-old boy with Stevens-Johnson syndrome was seriously ill with infection due to agranulocytosis on the 5th day of the disease. rhG-CSF (Cyugai rG·CSF) alone was given subcutaneously at the doses of 2μg/kg/day from the 9th day of the disease. No corticosteroids were administered. Granulocytes increased up to 7, 000/μl on the 13th day of the disease and his general condition was markedly improved. The serum G-CSF level was detected to be 8, 445 pg/ml during an agranulocytic period, which gradually decreased after the normal range of granulocytes was obtained. This case report indicates that treatment with rhG-CSF is beneficial for patients with Stevens-Johnson syndrome associated with agranulocytosis.

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It is known that acute leukemia with 11q23 chromosome abnormality has unique characteristics. In this paper we reported an infant acute leukemia with t (6; 11) (p21; q23). A 5-month-old boy presented in October 1989 with complaints of fever and vomiting. On clinical examination he was found to have hepatosplenomegaly. His WBC was 83, 600/μl with 58% blast calls. Based on cell morphology and cytochemical examinations, he was diagnosed as having acute myelomonocytic leukemia (AMMoL; FAB M4). Cytogenetic analysis showed 73% (11 of 15) cells with t (6; 11) (p21; q23). He was treated with adriamycin, cytosine arabinoside, 6-mercaptopurine and prednisolone and attained complete remission. However, CNS relapse occurred after 6 months. He was treated with another ANLL protocol and obtained second complete remission. While the translocation involving band 11q23 such as t (4; 11), t (9; 11) and t (11 ; 19) has been reported in the literature, t (6; 11) (q27; q23) has been reported in only three cases and this abnormality, t (6; 11) (p21 ; q23), is the first case.

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We report here a case of juvenile chronic myelogenous leukemia preceded by idiopathic thrombocytopenic purpura (ITP) -like thrombocytopenia. The patient was a one-year-old boy with thrombocytopenia, increased megakaryocyte in bone marrow and no other hematological abnormalities. Prednisolone was effective in this thrombocytopenia. About 7 months later, severe thrombocytopenia, monocytosis and leukoerythroblastosis in peripheral blood appeared without increased blast cells in bone marrow. After 5 months, juvenile chronic myelogenous leukemia was diagnosed by hepatosplenomegaly and hematological findings such as remarkable leukocytosis, especially monocytosis, and increased hemoglobin F of fetal type. ITP-like symptoms at clinical onset might be considered the preleukemic stage of juvenile chronic myelogenous leukemia.

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