The function of IgG antibody with regard to L-asparaginase (L-asp) was investigated in vivo. Blood samples were collected before, during and after IV administration of L-asp (6,000 U/sqm for 10days) in 18 children with acute lymphoblastic leukemia (ALL) previously treated with L-asp. Using enzyme-linked immunosorbent assay (ELISA), serum levels of L-asp and anti-L-asp IgG antibody were measured simultaneously. In 11 cases, the level of anti-L-asp IgG antibody increased prior to, but decreasd to within the normal range after drug administration whereas the level of serum L-asp increased after drug administration. In 5 cases, the level of anti-L-asp IgG antibody increased as the level of serum L-asp decreased after drug administration. In contrast, in the 13 cases with no increase in anti-L-asp IgG antibody during L-asp administration, the serum L-asp level was stable. These data indicate that anti-L-asp IgG antibodies play an important role in the immunoclearance of L-asp. We would like to continue to carefully follow patients showing high titers of anti-L-asp IgG antibody during the administration of L-asp.

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The efficacy of various combination chemotherapies employed for the 37 patients with low-grade non-Hodgkin's lymphoma between 1981 and 1994 was evaluated retrospectively. The overall survival at 5 years was 68%. The 5-year survival of the 27 patients achieving complete response (CR) was 87%, which was significantly higher than that of 9 patients with partial response (p=0.0005). The CR rate of stage III and IV patients was 64% for the 22 patients treated with ACOMP-B (D), and was 38% for 8 others treated with milder chemotherapy regimens including VEPA. The 22 advanced stage patients had a 5-year survival of 88% after the treatment with ACOMP-B (D) and 69% of them remained free of disease at 5 years. In this group no relapse occurred beyond 1.6 years after treatment. These findings suggest a possible role of third generation chemotherapy in the treatment of patients with advanced-stage low-grade non-Hodgkin's lymphoma.

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In performing cancer chemotherapy, it is essential to know the expression of multidrug resistant (MDR) P gycoprotein (p-gp) on cancer cells. In the present study, in order to clarify the relationship between MDR of leukemic cells and cytologic, immunological and clinical features of acute nonlymphocytic leukemia (ANLL), leukemic cells in peripheral blood and/or bone marrows obtained from 28 ANLL patients were examined. Each smear was stained with C219 monoclonal antibody against P-gp by the APAAP method, and then 1,000 ANLL cells in each smear were observed. Among the FAB subtypes, M4 showed the highest proportion of leukemic cells expressing P-gp. Concerning the response to chemotherapy, five of seven patients (71%) having 1.0% or more of P-gp positive leukemic cells and 11 of 19 patients (58%) having less than 1.0% of those cells achieved complete remission. However, there was no significant correlation between P-gp expression and clinical outcome. There was also no significant correlation between P-gp expression and CD7 or CD34. Furthermore, no significant correlation between chromosome 7 abnormality and P-gp expression was observed. From these results, if we can clarify the mechanism of MDR and the relationship between MDR and cytogenetic or clinical features of ANLL with further study, P-gp expression may become a useful marker for predicting the outcome of ANLL

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Blood genotyping was performed in three patients with ABO-group transformation hematological disorders. Serological examinations revealed the following A-subtype transformations: case 1 was AML with A₃B; case 2 was RAEB in transformation with A₃; case 3 was AML with A_int. Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis of the area flanking the two points 261 and 796 of the cDNA coding region revealed the genotypes of cases 1, 2 and 3 to be AB, AO, and AA, respectively. Four points in the cDNA coding region (467, 526, 703, and 871) were analyzed by PCR-RFLP to detect A-subtype-specific substitutions. Nucleotide position 467 is the substitution site for A-subtype allelic cDNA and 871 is the substitution site for the A₃-subtype. At nucleotide positions 526 and 703, non-isosemantic substitutions are known to take place between the A₁ and A_int alleles. No nucleotide substitutions specific to A-subtypes in this region were detected in any of the three cases. Thus, ABO blood group genotyping may be a useful way to distinguish between subtypes and transformations of phenotype.

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Concerning parenteral iron therapy in iron deficiency anemia, Nakao's formula has been used to calculate the total amount of iron to be given, based on 80 ml/kg of circulating blood volume and 17 mg/kg of storage iron in healthy Japanese. Recent studies using radionuclide and radioimmunoassay revealed 65 ml/kg as the circulating blood volume and 500 mg as storage iron. From these data, the total amount of iron can be calculated from the following formula; 3.4 (16-X)×65×body weight/100+500 mg (B) where 3.4 is the conversion factor for grams of hemoglobin to mg iron and X is the hemoglobin value before treatment. Parenteral iron therapy was performed in 15 patients with iron deficiency anemia using a total dose of iron calculated by the above the formula (B). The results were effective, and no decrease of hemoglobin was seen except in cases with continuous bleeding. In such cases, iron doses depending upon the amount of continuous bleeding should be added to the total amounts obtained from formula (B).

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Ten year old boy with acute promyelocytic leukemia (APL) was treated with all-trans retinoic acid (ATRA). Immediately after the oral administration of ATRA (nine mg/m² three times a day), DIC was controlled, and complete remission was achieved at day 39. The patient received ATRA therapy for 47 days, and then followed by conventional chemotherapy. Plasma ATRA level after 90 minutes of drug administration was 84.6 ng/ml. The superoxide generating activity of neutrophils in the bone marrow and peripheral blood was measured by chemiluminescence. The phagocytic function of neutrophils was markedly reduced in the ATRA-induced remission period, and was normal in the chemotherapy-induced remission. APL could be induced complete remission by three divided small doses of ATRA, and the ATRA-induced differentiated neutrophils might have lower phagocytic function.

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A 38-year-old female with acute myelogenous leukemia (M2) recieved an allogeneic bone marrow graft from an HLA-DR one locus-mismatched sister during the first remission. The conditioning regimen consisted of busulfan and cyclophosphamide. Acute graft-versus-host disease (GVHD) developed on day 11 after transplantation. Although the GVHD was successfully treated with methylprednisolone, peripheral blood neutrophils that had begun to increase disappeared in association with improvement of the GVHD and graft rejection was eventually diagnosed. The second bone marrow transplantation from the same donor ended up with engraftment failure. She died of sepsis due to Candida albicans following the development of Epstein-Barr virus-associated B-lymphoproliferative disorder. The clinical course of this patient indicates that successful therapy of severe GVHD with methylprednisolone may lead to marrow graft rejection.

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We report a patient with adult T-cell leukemia (ATL) complicated with intestinal tuberculosis. A 57-year old man was admitted to our hospital because of fever and dyspnea. He was diagnosed as ATL by leukocytosis [leukocyte count 18,200/μl with 56% of abnormal lymphocytes which express CD4(+) and CD25(+)] and seropositive result of anti-HTLV-1 antibody. Combination chemotherapy for ATL improved his serum LDH level and peripheral lymph nodes, but fever was still persistent. He had an emergency operation because of perforation of the cecum during the chemotherapy. Histological examination of the resected cecum revealed caseous necrosis and numerous mycobacterium, which induced a diagnosis of intestinal tuberculosis. Although there have been several reports on pulmonary tuberculosis in patients with ATL, this is the first report of intestinal tuberculosis in ATL as far as we know. We conclude that if the patients with ATL have persistent fever of unknown origin, we should take account of intestinal tuberculosis as one of differential diagnosis.

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A 57-year-old woman was admitted to our hospital complaining of left exophthalmos in July, 1991. Biopsy specimen of a tumor in the left orbit suggested an inflammatory pseudotumor. The orbit was irradiated and the exophthalmos disappeared. During admission, an erythema was noted on her anterior chest wall. After discharge, right exophthalmos and generalized skin eruptions developed. The skin eruption on her anterior chest wall was histopathologically diagnosed as angiocentric lymphoma and she was readmitted. Since her serum was positive for anti-HTLV-I antibody, adult T-cell leukemia/lymphoma was suspected. Chemotherapy yielded limited relief of the right exophthalmos and transient fading of the skin eruptions. She died due to progression of the disease. Close examination of the skin eruption on the calf revealed that the lymphoma cells were CD56-positive immunohistochemically and electron microscopy revealed that they had large membrane-bound granules. Rearrangement of the T-cell receptor β chain gene was observed. Incorporation of HTLV-I proviral DNA was not observed. Re-examination of the left orbital tumor confirmed the infiltration of these lymphoma cells. This is a rare case of T-cell lymphoma with NK cell phenotype involving orbits and skin, and showing a rapid clinical course.

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A male patient with severe aplastic anemia was admitted for bone marrow transplantation. While waiting for a donor, high doses of methylprednisolone, anabolic steroid and granulocyte colony stimulating factor were given without response. Deferoxamine was administered for prophylaxis of hemochromatosis because of high level of ferritin. Acute right lower abdominal pain and pyrexia developed. A diagnosis of acute appendicitis was made and appendectomy was performed. The histopathological examination of the resected appendix revealed necrotizing hemorrhagic appendicitis with numerous hyphae of Mucorales. Though anti-fungal agent (amphotericin B) administration was continued, he subsequently developed ileo-cecal abscess and eventually died due to myoglobinuric nephropathy caused by extensive necrosis of the iliopsoas muscle. Autopsy revealed dissemination of hyphae of Mucorales in lungs, kidneys, large vessels and muscle of the bilateral lower limbs. Systemic vascular invasion and embolization of fungal hyphae were also observed. However, culture of exudate sampled from ileocecum yielded no Mucorales. It was emphasized that antemortem diagnosis and effective anti-fungal treatments are essential for the management of intestinal mucormycosis. The relation ship between mucormycosis and deferoxamine was also discussed.

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A 46-year-old man with idiopathic thrombocytopenic purpura (ITP) refractory to corticosteroid, splenectomy and other drugs was admitted to our hospital in August, 1994, because of aseptic necrosis of the right femoral head. Although high-dose intravenous gamma-globulin was ineffective, the platelet count was increased within two weeks by the combination therapy that consisted of 0.02 mg/kg vincristine alternating with 0.1 mg/kg vinblastine by slow infusion at a 1-week interval, and oral 1.5 mg/day colchicine. He subsequently underwent the femoral head replacement. This combination therapy seems to be useful for refractory ITP in preparation for surgery.

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An 84-year-old female was admitted to our hospital because of fever. Physical examination and computed tomography revealed hepatosplenomegaly without lymphadenopathy. Anemia and thrombocytopenia were noted and the serum levels of LDH, IL-6 and sIL-2R were elevated. Bone marrow aspiration showed infiltration of lymphoma cells and proliferation of histiocytes with hemophagocytosis. Southern blot analyses revealed rearrangements of both IgJH and IgJK genes. She received corticosteroids with improvement of her general state but she died on the 110th hospital day. Necropsy of the spleen showed diffusely proliferating large lymphoma cells, immunoreactive for B cell marker L-26, and scattered histiocytes with hemophagocytosis.

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