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Ichiro TSUKIMOTO
1993 Volume 7 Issue 3 Pages
177-186
Published: June 30, 1993
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The major uses of transfusion therapy in the children have been treatment of hematologic and malignant disease, cardio-vascular surgery and neonatal anemia. Transfusion therapy in children differs in many respects from transfusions in adults. The relatively smaller size of children permits a broad spectrum of transfusion technology, particularly as regards exchange transfusion or autologous transfusion. Some donated blood is collected into specific pediatric multiple-pack systems to minimize the number of donors. The complication rate related to transfusions may differ remarkably from that seen in adults. An example of this is much greater incidence of graft-versus host disease and cytomegalovirus infection following transfusion therapy in children. The objectives of this paper are to review (1) the hematophysiology of the children, especially in the newborn ; (2) transfusion therapy of the children employing whole blood or separated blood products such as red cells, platelets, granulocytes and plasma ; and (3) the causes and prevention of transfusion related infections and graft-versus-host disease.
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A Trial of Three Modalities of Therapy for Groups Classified According to Stage and Histology
Keiko NIBU, Fumio YANAI, Masahiro KIKUCHI, Eiichi ISHII, Kohji UEDA, Y ...
1993 Volume 7 Issue 3 Pages
187-193
Published: June 30, 1993
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Children with non-Hodgkin's lymphoma (NHL) were stratified into groups according to their histology and stage, and were treated with three treatment regimens which included different schedule of chemotherapy and central nervous system prophylaxis. Between 1985 and 1988, 28 patients were treated. All were diffuse type NHL, of which 9 cases were localized (stage I and II), and 19 were advanced (stage III and IV) NHL. Twenty-five of the 28 cases (89%) achieved complete remission. During maintenance phase, however, 8 cases relapsed (4 were in the bone marrow). Seventeen cases completed 2-year duration of therapy, among which only 1 case relapsed thereafter. At a median observation period of 61 months, disease-free survival (DFS) and overall survival for all cases at 60 months were 52% and 61%, respectively. The patients of the first group with large cell histology (stage I-IV) and lymphoblastic histology (LBL) (stage land II) received no prophylactic cranial irradiation. They did not relapse beyond 23 months after diagnosis and DFS was 70%. The patients of the second group with small non-cleaved histology (SNC), Burkitt type (stage I-IV) and NHL with abdominal mass (either LBL or SNC, stage I-IV) were treated with intensive chemotherapy and intrathecal medication. This group showed DSF of 57% (No relapse occurred beyond 4 months). The patients of the third group, mainly LBL with mediastinal mass, showed stepwise relapse until 37 months and DFS was 25% at 60 months, which was the worst among the 3 groups.
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Hiroshi KUWABARA, Toshiki OHKUBO, Masamune HIGASHIGAWA, Minoru SAKURAI
1993 Volume 7 Issue 3 Pages
194-198
Published: June 30, 1993
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We studied the effect of 4'demethylepipodophyllotoxin 9- (4, 6-O-ethylidene-β-o-glucopyranoside) (etoposide) on influx and accumulation of 1-β-D-arabinofuranosylcytosine (ara-C) and 6-mercaptopurine (6MP) in several cell lines, including P388 murine leukemic cell line, and human acute lymphoblastic leukemia (ALL) cells. 1) Influx of ara-C and 6MP was inhibited by etoposide in a dose-dependent manner. 2) Accumulation of ara-C and 6MP was also inhibited by etoposide in a dose-dependent manner. 3) The IC
50 was defined as the concentration of etoposide that inhibits influx or accumulation by 50% as compared with untreated control. The IC
50 of accumulation was higher than that of influx in leukemic cell lines. On the other hand, the influx and accumulation in human ALL cells were inhibited by etoposide to the same extent. We concluded that much attention to the timing of administration of etoposide and ara-C or 6MP might be needed in chemotherapy of human ALL.
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Mitsuru IMAI, Kouichi INOUE, Yasuzou HIROTA, Keiichi ISOYAMA, Kouichir ...
1993 Volume 7 Issue 3 Pages
199-204
Published: June 30, 1993
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The effects of recombinant human growth hormone (rhGH) on the colony-forming unit granulocyte/macrophage (CFU-GM) in human umbilical cord blood were studied. In conventional semisolid cultures, rhGH had no effect on CFU-GM. However, in serum-free liquid cultures, CFU-GM increased by the addition of rhGH under the presence of rhIL3. Furthermore, increased proliferating cell nuclear antigen (PCNA) -positive cells were observed in the presence of rhGH. A good correlation between the total number of CFU-GM in liquid culture and PCNA-positive cells ratio was observed. These results suggest that rhGH might promote the proliferation and differentiation of hematopoietic stem cells into CFU-GM.
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Takeshi SUZUE, Yoichi TAKAUE, Takashi SHIMIZU, Yasuhiro OKAMOTO, Shin- ...
1993 Volume 7 Issue 3 Pages
205-209
Published: June 30, 1993
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Twenty-six children (1-16 y ; median, 8y) with acute lymphoblastic leukemia (ALL) underwent high-dose chemotherapy without total body irradiation and autologous peripheral blood stem cell transplantation (PBSCT). Five patients with delayed initial induction underwent PBSCT in the first complete remission (CR) after second-line induction therapy. Twelve patients underwent PBSCT in the second CR, and 4 in subsequent remission (advanced CR). Five patients were treated at refractory relapse. After PBSCT, the median number of days required to achieve a white blood cell count of 1000/μl, a granulocyte count of 500/ μl and a platelet count of 5 × 10
4/μl were, respectively, 13, 13, and 16. Fifteen patients developed relapse of the leukemia, but the remaining 11 patients are surviving disease-free for 2 to 56 months posttransplant. The data justify the incorporation of PBSCT in the treatment of children with ALL associated with high-risk features.
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Susumu KAWAI, Takeo FUJIMOTO, Zhimin ZHA, Asayuki IWAI, Ken SUZAKI, Hi ...
1993 Volume 7 Issue 3 Pages
210-216
Published: June 30, 1993
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Frequency and clinical significance of myeloid associated antigens expression in blast cells were assessed in 198 consecutive children with acute lymphoblastic leukemia (ALL). Thirty cases (15.5%) reacted with at least one myeloid monoclonal antibodies (CD 13 and CD33). In comparison of clinical features between My
+ALL (myeloid antigens positive ALL) and My
-ALL (myeloid antigens negative ALL), the mean age at onset was 7.0 years for My
+ALL and 6.3 years for My
-ALL. The mean initial white blood cell count was 96.4 × 10
3/μl for My
+ALL, which was higher than the 80.0 × 10
3/μl for My-ALL. Twenty patients (67%) with My+ALL were stratified to “high-risk group ALL.” The 3 years event-free survival rate (EFS) was 56.2%± 10.4% for My
+ALL, which was lower than the 76.7%±3.6% for My
-ALL. But, the difference was not statistically significant. The 3 years EFS rate for Ph
1 + ALL (
n=5), CD 13
+, CD33
-ALL (
n=11), CD 13
-, CD33
+ALL (
n=5), CD 13
+, CD33
+ALL (
n=9) were 0%, 100%, 42.7% and 53.5%, respectively. The Ph
1+ALL patients and CD33
+ALL (
n = 14) patients had worse prognosis than My-ALL patients. Further studies are required to determine the prognostic significance of CD33 expression in blast cells.
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Ryoji KOBAYASHI, Hideki ARIOKA, Hiroyuki NAITO, Takaaki SHIKANO, Yorik ...
1993 Volume 7 Issue 3 Pages
217-220
Published: June 30, 1993
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In 55 treatment histories of 24 leukemia and lymphoma children with non-remission state, 12 cases had acute tumor lysis syndrome (ATLS). ATLS was defined as complication of either hyperuricemia (>10 mg/dl), hypocalcemia (<7 mg/dl) or hyperphosphatemia (>7 mg/dl) after initiating antineoplastic agents. Pretreatment LDH was higher in ATLS group (
n=12) than non-ATLS group (n=43) and many patients of ATLS group had organomegaly in pretreatment state. Pretreatment FEUA (fractional excretion of uric acid) was higher in ATLS group, but they were not statistically different. %TRP (% tubular reabsorption of phosphorus) was also lower in ATLS group, but they were not statistically different, because of small study size. FEUA and %TRP may be useful adjunct in supporting estimation of occurrence of ATLS in pretreatment state.
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Ryoji KOBAYASHI, Hideki ARIOKA, Hiroyuki NAITO, Takaaki SHIKANO, Yorik ...
1993 Volume 7 Issue 3 Pages
221-225
Published: June 30, 1993
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Fourteen cases of acute tumor lysis syndrome (ATLS) complicated with leukemia and lymphoma were described. Acute tumor lysis syndrome was defined as complication of either hyperuricemia, hyperphosphatemia or hypocalcemia after initiating antineoplastic agents. Hyperphosphatemia was observed in all cases, but hyperuricemia was only in 9 cases. Patients with hyperuricemia were relatively younger and many of them were in first induction therapy of acute lymphoblastic leukemia (ALL), and achieved high rate of complete remission. Patients without hyperuricemia were all above 10 years old and almost all were relapse case or chronic myelocytic leukemia (CML) in blastic crisis. Maximum values of uric acid and LDH were well correlated and high CR rate was obtained in the cases having these high values.
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Study of Combination Therapy of Cyclosporine, Antilymphocyte Globulin and Methylprednisolone
Yorikazu ISHIKAWA, Hideki ARIOKA, Ryoji KOBAYASHI, Hiroyuki NAITO, Yos ...
1993 Volume 7 Issue 3 Pages
226-229
Published: June 30, 1993
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We compared retrospectively the treatment with combination of cyclosporine A (CyA), antilymphocyte globulin (ALG), and methylprednisolone (mPSL) to single or combination of 2 drugs from these 3 immunosuppressive drugs in patients with aplastic anemia (AA). Sixteen patients with AA (8 severe, 8 moderate type) were treated. Complete responses of initial treatment were shown in 3 of 4 patients treated with a combination of 3 drugs and in only 1 of 12 patients treated with 1 to 2 drugs within 3 months. Patients who did not respond at initial treatment were given other immunosuppressive drugs. Finally 27 times of the treatments in 16 patients with AA were done. Four of 6 cases treated with 3 drugs and 3 of 21 cases treated with 1 to 2 drugs were effective. Serious side effects were not observed in the combination therapy of these three drugs. This therapy appears to be beneficial and may be used as initial treatment for patients with aplastic anemia.
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Yuji MIYAJIMA, Shin-ichiro NUMATA, Isao KATAYAMA, Keizo HORIBE
1993 Volume 7 Issue 3 Pages
230-235
Published: June 30, 1993
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We reported 14 cases of childhood acute lymphoblastic leukemia (ALL) with hyperleukocytosis (> 10 × 10
4/μl) at diagnosis. Two cases were less than one year old and three were more than nine years old. Immunophenotypically, eight cases were common ALL, five were T cell ALL and one was null ALL. Structural abnormality in karyotype of leukemic cells was seen in nine cases. At presentation, serum lactate dehydrogenase was more than 1000 IU/l in ten cases, marked hepatosplenomegaly was seen in ten and leukemic infiltration to the central nervous system was seen in two. All cases received vigorous hydration with sodium bicarbonate and oral allopurinol. Five patients received steroid therapy prior to intensive chemotherapy, but neither leukapheresis nor exchange transfusion was not done in any case. Complications during induction therapy were as follows : hypocalcemia in five cases, hyperkalemia in two and coagulopathy in five. However, neither complications associated leukostasis nor tumor lysis syndrome was experienced in any case. Complete remission rate was 78.6%. Nine of 14 cases have remained in the first remission for 23 to 93 months, as of March, 1993. Five-year event-free survival estimated by Kaplan-Meier method was 64.8%. In conclusion, prognosis of ALL with hyperleukocytosis has improved with intensive chemotherapy, but patients with special chromosomal translocation, i.e., t (9;22) and t (9;11) still had a poor prognosis.
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A Case Report and an Overview of the Cases in Japan
Masato SAITOH, Keigo NAKATANI, Naoki TACHIBANA
1993 Volume 7 Issue 3 Pages
236-240
Published: June 30, 1993
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A case of acute lymphoblastic leukemia accompanied by severe acute pancreatitis is reported. A 5-year-old boy was admitted with diagnosis of common type ALL. The patient was started on treatment according to Tohoku Pediatric Leukemia Study Group Protocol ALL89A. This included weekly intravenous vincristine, daily oral prednisolone, and
Escherichia coliL-asparaginase 6, 000 IU/m
2intramuscularly. Ten days after starting L-asparaginase, a clinical picture of an acute pancreatitis appeared with abdominal pain, nausea and vomiting. Physical examination revealed severe abdominal distension with pleural effusion and ascites. Serum and urine amylase level had arisen 1, 352 IU/l and 9, 748 IU/l respectively. CT scan revealed marked enlargement of pancreas and mild fatty liver. After symptomatic treatment, the patient recovered. Previous reports with L-asparaginase-induced pancreatitis in Japan were also reviewed.
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Kiriko TOKUDA, Nobuyuki KODANI
1993 Volume 7 Issue 3 Pages
241-244
Published: June 30, 1993
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We report a case of acute lymphoblastic leukemia with vertebral compression fractures. A 14-year-old male presented with 2 months' history of gradually progressing back pain, and associated X-ray evidence of vertebral compression fractures. A bone marrow aspiration and biopsy revealed infiltration with L 1 (FAB classification) lymphoblasts. After remission had been achieved by antileukemic treatment, his back pain disappeared despite persistence of spine abnormalities on repeat radiologic examinations. Vertebral compression fracture is a rare manifestation with childhood ALL. But it is often associated with good prognosis.
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Yoshiki SATOH, Takamichi UMENAI, Junko WATANABE, Jun'ichi KITAZAWA, Yo ...
1993 Volume 7 Issue 3 Pages
245-250
Published: June 30, 1993
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An 11-year-old boy was admitted to our department for testicular relapse of ALL. Testicular irradiation and reinduction therapy according to PVDA III regimen were administered and severe hyperlipemia of type V (WHO Classification) developed during a two-week course of L-asparaginase (10000 IU/m
2/day). When the patient was given reinforcement chemotherapy including L-asparaginase, he showed remarkable hyperlipemia again. The serum triglyceride reached 9, 208 mg/dl and LDL apheresis was performed. Plasma lipoprotein disk electrophoresis disclosed a marked increase in the VLDL fraction and a decrease in the LDL fraction. Plasma level of apo-lipoprotein C-III fraction, which is considered to inhibit lipoprotein lipase (LPL), increased remarkably. We observed that the administration of L-asparaginase made no significant change in the plasma activity of LPL and tended to decrease the plasma activity of hepatic triglyceride lipase (HTGL). HTGL is generally considered to catabolize chylomicron remnant and IDL. It suggested that HTGL played some part in this abnormality of fat metabolism
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Taketora ECHIZENYA, Hiroshi FUJITA, Mihoko OOTUKA, Kiyoshi CHIBA
1993 Volume 7 Issue 3 Pages
251-256
Published: June 30, 1993
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A case of low titer cold agglutinin disease with rapidly severe hemolytic attack, which occurred after suffering from rubella, is reported. A 7-year-old girl visited the outpatient clinic of Mutsu General Hospital becuse of fever and exanthema on January 24, 1992 ; she was diagnosed as having rubella. She was admitted with appearance of icterus on January 27, 1992. Examination of the blood showed a hemoglobin 8.6 g/dl, but that dropped rapidly to 3.0 g/dl after 2 days. Blood chemistry findings revealed increased serum indirect bilirubin, serum LDH3 value and decreased serum haptoglobin. Broad-spectrum direct anti-globin test was strongly positive at low (4°C) and room temperature, and weakly positive at body temperature (37°C). Anti-IgM antibody was detected by dithiothreitol test. Serological markers for rubella virus were positive. Cold agglutinin titer was 1 : 256, but the hemolysis occurred near body temperature because cold agglutinin thermal amplitude was broad spectrum. Hence the diagnosis of low titer cold agglutinin disease with rubella virus infection was made.
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Mitsuyoshi URASHIMA, Kanako ANZAI, Yoko KATOH, Hiroshi UCHIYAMA, Kohji ...
1993 Volume 7 Issue 3 Pages
257-262
Published: June 30, 1993
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We experienced a 6-year-old boy with chronic myelomonocytic leukemia (CMMoL) as a part of myelodysplastic syndrome. He was admitted with fever, vomiting, general fatigue, and peripheral blood leukocytosis. Monocyte-like cells were increased and 1.0% blast cells were recognized in the peripheral blood. All stages of myeloid cells with evidence of dysgranulopoiesis were increased and 4.0% blast cells were recognized in the bone marrow. Erythroid cells also showed morphological abnormalities. Ara-C continuous therapy was applied, but repeated remissions and relapses occurred. An acute crisis developed 1 year and 2 months after the onset. He died three months after the acute crisis.
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Chika NAKAJIMA, Seiji KOJIMA, Kimikazu MATSUMOTO, Koji KATO, Takaharu ...
1993 Volume 7 Issue 3 Pages
263-267
Published: June 30, 1993
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Several studies using alternative donors have been carried out to improve the survival rate in patients with severe aplastic anemia who do not have an HLA identical sibling. We report a 4-year-old male with heptitis-associated aplastic anemia who received an allogeneic bone marrow graft from an HLA DR mismatched 7-month-old brother. The patient was prepared with cyclophosphamide combinated with 500 cGy total lymphoid irradiation and 500 cGy total body irradiation. We used a combination of cyclosporin plus methotrexate for the prophylaxis of graft-versus-host disease (GVHD). Although the patient engrafted promptly, he developed acute GVHD (grade III), which was treated with high dose methylprednisolone. He has had full hematopoietic recovery and no signs of chronic GVHD for 16 months following bone marrow transplantation.
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Masami YAMATANI, Ken SUZAKI, Hiromichi KUBOTA
1993 Volume 7 Issue 3 Pages
268-273
Published: June 30, 1993
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Clinical and laboratory features of a patient with acute lymphoblastic leukemia are presented. A 13-year-old girl presented a few weeks history of fatigue and anemia. White blood cells were310×10
4/l consisting of 5% neutrophils and 95% blasts. The bone marrow aspirates were hypercellular and replaced by 91.7% L2 lymphoblasts which were negative for myeloperoxidase and non-specific esterase. Surface marker analysis revealed that leukemic cells expressed CD22, CD19 and CD38 antigens, but not CD10 antigen. The patient's leukemic cells had both the t (4 ; 11) and t (9 ; 22) chromosomal translocations. Gene rearrangement of Ig heavy chain was demonstrated, but Ig light chain and beta-TCR gene rearrangement were not found. No rearrangement of bcr3' and bcr5' was identified. Complete remission was achieved after 4 weeks induction therapy. After three months of chemotherapy she relapsed. In spite of reinduction therapy, the patient did not respond considerably and died 2 months later. To our knowledge, this is the first case having two chromosomal translocations t (4 ; 11) and t (9 ; 22).
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Hisamichi TAUCHI, Yasushi ISHIDA, Tetsushi INOUE, Yoshiko YOKOTA, Hiro ...
1993 Volume 7 Issue 3 Pages
274-277
Published: June 30, 1993
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The patient, a 1-year-5-month old boy, was referred to our hospital because of fever, lymphadenopathy, hepatosplenomegaly and pancytopenia. Serum ferritin and LDH levels were elevated on admission. The patient was treated with etoposide for 3 days following exchange transfusion because of DIC and consciousness disturbance. His symptoms and laboratory data improved promptly after treatment and he has been disease-free for more than 2 years without any further therapy. The diagnosis of virus-associated hemophagocytic syndrome (VAHS) was made from his clinical course and antibody titers to Epstein-Barr virus (EBV). However, the bone marrow findings were compatible with those of malignant histiocytosis (MH) by the definition of Manoharan et al.
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1993 Volume 7 Issue 3 Pages
279
Published: 1993
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