Clinical and cytological features of CD7 positive acute leukemias with biphenotypic characteristics in childhood were documented. From 87 patients with CD7⁺ acute leukemias, nine patients were selected on the basis of the biphenotypic expression of T-lymphoid and myelomonocytic antigens. The blasts of these patients expressed cell surface CD7, cytoplasmic CD3 and cytoplasmic CD13. In addition to these antigens, surface CD13 was also expressed after short term culture without any mitogens or stimulators. The double PAP method for detecting cytoplasmic antigens (CD3, CD13, βF1, δTCS1) was employed in this study. The average age of these patients was higher (10.2 y/o) than patients with common ALL. Mediastinal masses were observed in 4 of 9 patients. They were treated according to the diagnoses based on conventional hematological methods and surface antigen expression. In all 9 patients, complete remission was achieved, however, early relapse was noticed in 7. This study suggests that the leukemia cells of these patients may be derived at an early stage during the differentiation of multipotential hematopoietic stem cells. New therapeutic approaches are necessary to improve the outcome of such T/M biphenotypic leukemias.

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To investigate the physio-pathological functions of HC-II, assays for HC-II and AT-III were performed simultaneously on the samples from patients with DIC, liver dysfunction or renal disease from the three view points of consumption, production and loss of AT-III and HC-II. For the AT-III activity, two kinds of assays were applied: the automatic chromogenic substrate method and a newly developed clotting method which receives no effects from HC-II activity. The activity of HC-II was siginificantly lower than that of AT-III in patients with either DIC or liver dysfunction. However, no significant difference between HC-II and AT-III activities in patients with either thrombosis or renal disease. There were high correlations between HC-II and AT-III activities were found in the patients with liver dysfunction, suggesting that low activity was due to decreased production of HC-II and AT-III in the liver. It will be necessary that elucidation of the significant functions of HC-II not only in coagulation and hemostasis but also in regulation of local inflammation and invasion of neoplasm is necessary.

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We evaluated an initial activation of hemostasis (coagulation, fibrinolysis and kallikrein-kinin system) in two remarkable eosinophilia cases. The first case was a 29-year-old male who complained of a high fever, general exanthema and numbness of the limbs. He had peripheral blood eosinophilia (61,075/μl) unknown etiology, and hypereosinophilic syndrome (HES) was diagnosed. The second case was a 60-year-old female who complained of numbness in her lower limbs. She also presented eosinophilia (10,379/μl), and had clinical features of allergic granulomatous angitis (AGA). The administration of prednisolone led to clinical remission in both cases, including rapid improvement of eosiniphilia, normalization of hypercoagulability and correction of platelet dysfunction. In hemostatic parameters, the titer of the soluble fibrin monomer complex (SFMC) became negative, and each value of FDP D-dimer, fpBβ 15-42, thrombin-antithrombin III complex (TAT) decreased, whereas the value of prekallikrein increased. A decrease in platelet aggregation with ADP, collagen and epinephrine was normalized by prednisolone administration. Hemostatic data in both cases indicate a possible relationship between the initial activation of hemostasis and the eosinophils, as well as the possibility of general and/or organic inflammations and intravascular thrombi formations in eosinophilia such as HES and AGA.

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A study was performed in 62 patients with non-Hodgkin's lymphoma (ATL included) who were hospitalized between 1985 and 1991 and who underwent bone marrow aspiration and biopsy before or after treatment or at the time of recurrence. The relationships between the extent of bone marrow fibrosis and other prognostic factors as well as the effects of chemotherapy and bone marrow fibrosic prognosis were examined. The results were as follows: 1) The periods of survival in patients with high degree of fibrosis in bone marrow were significantly shortened. 2) The extent of bone marrow fibrosis significantly correlated with the presence or general symptoms, bone marrow invasion, and blood levels of LDH and Ca on blood biochemical examinations. 3) Effective therapy reduced collagen fibers as well as reticulin fibers in bone marrow. 4) Sixty-four percent of relapsing cases showed increase of bone marrow fibrosis. These results suggest that understanding the state of bone marrow fibrosis over the clinical course may give a good guide of indication the prognosis of malignant lymphoma.

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One hundred patients with diffuse non-Hodgkin's lymphoma were treated with combination chemotherapy including adriamycin. Seventy-one patients were under age 70 and 29 were 70 years or older. The clinical characteristics of the two groups were similar, except that the patients showed elevated serum BUN were in the elderly group. The complete remission rate in the elderly patients (66%) was slightly lower than that in the younger patients (75%) (p=NS). The average length of survival in the elderly patients was significantly shorter than in the younger patients (p<0.05) (projected 5-year survival: 28±11% vs 52±7%). The duration of remission for all patients in the elderly patients did not differ from that in the younger patients (projected 2-year survival: 40±10% vs 45±6%). Death during the induction chemotherapy from causes other than lymphoma occurred in 14% of patients over 70-year-old and in one percent of younger patients. At relapse, the response rate was significantly lower in the elderly patients than in the younger patients (CR+PR: 28% vs 78%, p=0.03). To prevent toxic death in remission induction therapy, drug dose elderly patients should be attenuated according to their general conditions and performance status.

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The expressions of human T-lymphotropic virus type I (HTLV-I) mRNA in the HTLV-I-infected lymphocytes were studied in the peripheral blood of two HTLV-I carriers and of three patients with adult T-cell leukemia (ATL) (acute, chronic and lymphoma types) by in situ hybridization technique using two biotinylated single-stranded oligodeoxynucleotide probes complementary to different nucleotide sequences in the mRNA for the HTLV-IpX region. A low percentage of leukocytes (1.5∼7.4%) reacted with the probes in ATL patients, while <1% of leukocytes was reactive in HTLV-I carriers. These results indicate that a part of ATL cells express the HTLV-IpX, which is thought to be involved in the leukemogenesis of ATL in the peripheral blood of the patients.

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To test the safety of infusing cryopreserved and thawed peripheral blood stem cells (PBSC) in children, toxicity assessment was made at 36 infusions in 33 children with various types of cancer. The mean volume of PBSC graft infused was 224 ml (range, 46∼500 ml) or 8.0 ml/kg (1.7∼23.8 ml/kg), in containing 10% dimethylsulfoxide (DMSO). Vomiting was the only toxic feuture related to the amount of DMSO. However, eight patients developed transient shock, put recovered shortly afterward with or without supportive therapy. Attention should be drawn to increased risk in children receiving thawed blood cell grafts.

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The authors report an 18-year-old female who developed severe hemolytic reaction and delayed neutrophil recovery after bone marrow transplantation (BMT) for aplastic anemia from her HLA-identical sibling. She had received much transfusion (61 units of red blood cells including 4 units of fresh whole blood from her parents and 350 units of platelets) for 12 years before BMT. To prevent graft rejection, she received an intensified preparative regimen consisted of cyclophosphamide 200 mg/kg followed by 5 Gy total body irradiation and 5 Gy total lymphoid irradiation. Prophylaxis for GVHD was short term methotrexate and cyclosporin-A. Despite of the removal of the red cells from the marrow, marked hemolytic reaction caused by antibodies directed to rh" (E) and hr' ( ?? ) red cell antigens was observed when rh" (E) and hr' ( ?? ) positive donor erythroids began to recover. The recovery of neutrophils, especially the fraction of segmented cells was also delayed. Flow cytometry showed that the serially collected patient's sera reacted to neutrophils derived from both patient's blood on the 64th post-transplant day and the donor's blood. The reactivity was strongest in pre-BMT sera. We conclude that residual antibodies sensitized before BMT are a major cause of these hematological problems.

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A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/μl). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysacchalides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Antineutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term malnutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 μg/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (<60 pg/ml). It is effective to administrate G-CSF to anorexia nervosa with neutropenia.

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A rare case of hemolytic anemia complicated with Behçet's disease and myelodysplastic syndrome (MDS) is described. A 41-year old woman suffering from hemolytic anemia was admitted in July of 1988 with right lower abdominal pain and a high fever. Her anemia was first pointed out in 1962 (at age 15), and diagnosed as hemolytic anemia in 1977 by a full hematological examination showing erythrohyperplasia in bone marrow, Coomb's test was negative and corticosteroid therapy failed to improve her anemia. She had also been suffering from recurrent stomatitis and genital ulcer since the delivery of her first baby in July, 1972. Barium enema was performed and revealed a simple deep ulcer at the terminal ileum. Bone marrow examination showed morphological abnormalities of granulocytic and erythrocytic series. We thereby diagnosed her illness as incomplete Behçet's disease and MDS associated with hemolytic anemia. She was treated by ubenimex, blood transfusion and intravenous alimentation with discontinuing oral intake, and there was a satisfactory improvement in pancytopenia and ulcer.

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Prognosis of second marrow transplantation after leukemia relapse is usually gloomy. We report a patient with AML who was successfully treated by the second marrow transplant following high dose busulfan, etoposide, and Ara-C for the testicular relapse after the first marrow transplantation. A 24-year-old man was diagnosed as having acute myeloid leukemia (AML) in September, 1988. In December of 1989 when he was in early relapse after his 2nd remission, he received the first allogeneic BMT from his HLA identical brother after high dose busulfan and cyclophosphamide conditioning. His posttransplant course was uneventful and graft versus host disease was not observed. Three months after BMT, he noticed swelling on right testicule. Leukemic cell infiltration was confirmed by aspiration cytology. The testicular relapse was followed by marrow relapse. After successful remission induction chemotherapy, he received 17.5 Gy testicular irradiation and second marrow transplantation using high dose busulfan, etoposide, and Ara-C conditioning. Although his posttransplant period was complicated by severe mucositis, high fever and bronchopneumonia, hematologic recovery was obtained by 3 weeks after the second transplant. He is now continuing in complete remission 18 months after the second BMT. This case report suggests that the combination of high dose busulfan, etoposide, and Ara-C could be a choice as a conditioning regimen for resistant AML relapsing after BMT.

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A 48-year-old female received serial combination chemotherapy including L-asparaginase (L-ASP) for acute lymphoblastic leukemia. After administration of L-ASP, the prothrombin time and activated partial thromboplastin time were prolonged, while fibrinogen and antithrombin III levels markedly decreased, so she was given fresh frozen plasma (FFP). But subsequently, she developed cerebral infarction in the left parietal region and further hemorrhagic infarction in the right parietal region, and died. Autopsy revealed superior sagittal sinus thrombosis and bilateral cerebral infarction, but no obvious thrombus in other organs. Coagulopathy following L-ASP therapy is well-known. In this case, the coagulation studies at the first attack showed that the plasma protein levels of coagulation and fibrinolysis factors decreased in spite of administration of FFP. Fibrin-fibrinogen degradation products (FDP) slightly increased. However there were no significant abnormalities in the platelet count, nor soluble fibrin monomer, which suggested no evidence of disseminated intravascular coagulation. Thus, these findings suggest that L-ASP might be associated with the pathogenesis of thrombosis in this case.

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In a 4-year-old girl having acute megakaryoblastic leukemia, recombinant human granulocyte colony-stimulating factor (G-CSF) was used in combination with chemotherapy for remission induction after the second relapse of her leukemia. G-CSF was given intravenously at a dose of 100μg/m²/day 24 hours prior to chemotherapy until the peripheral neutrophil counts fully recovered. Cytosine arabinoside (Ara-c) [100mg/m²/day] and VP-16 [100mg/m²/day] were given from day 1 through day 10. Her leukemia was resistant to chemotherapy alone after the second relapse but complete remission and hematological recovery were achieved two months after the start of this therapy. Although in vitro clonal assay did not show significant stimulation of colony formation by G-CSF on leukemia cells of this patient, and the mechanism underlying remission induction by this combination therapy remains unclear, it may be of benefit to use G-CSF in combination with chemotherapy for patients with drug-resistant leukemia.

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Severe respiratory distress appeared in a 14-year-old girl with acute lymphoblastic leukemia 2 months after receiving syngeneic bone marrow transplantation (BMT) with a conditioning regimen of a high-dose of busulfan, etoposide and nimustine. Rapid body-weight gain and edema, especially in eyelids and lower-limbs, were also observed. Without any findings of heart failure nor GVHD, pulmonary edema was recognized on the chest roentgenogram. As soon as the diagnosis of pulmonary edema due to ‘capillary leak syndrome’ was suspected, the patient was treated with intravenous administration of diuretics, albumin and bolus methylprednisolone in combination of mechanical ventilation. Although the clinical manifestations were improved by the treatment, the disease recurred 5 weeks later. The patient was successfully treated by the same medications, and there has been no recurrence as of the sixth month after discontinuance of the therapy. At present, the mechanism of capillary leak syndrome is still undefined. In this case, however, we speculate that the conditioning regimen for BMT intensified the capillary disturbance initially caused by intensive chemotherapy since remission induction. Furthermore hypoalbuminemia due to severe anorexia might have enhanced the occurence of the disease.

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The authors report an autopsy case of CD3^- large granular cell leukemia with an aggressive clinical course. A 15-year-old male was admitted to our hospital with complaint of high fever. Clinical examination revealed cervical lymphadenopathy and hepatosplenomegaly. His white blood cell count was 7,000/μl with 45% large granular lymphocytes. A biopsy specimen of the cervical lymph node showed diffuse lymphoma, mixed small and large cells (DM). Surface marker analysis by immunohistochemical technique revealed that neoplastic cells expressed CD2, CD38, CD56 and HLA-DR but lacked CD3, CD4 and CD8. Southern blot analysis of immunoglobulin (Ig) and T cell receptor (TCR) genes showed germ line of Ig and TCR. These findings indicate that this case was a large granular cell leukemia with the natural killer cell phenotype. Despite anti-leukemic therapy, he died of hyperkalemia and acidosis. Autopsy showed a marked swelling of the liver (3,122 g) and spleen (2,434 g) with leukemic cell infiltration.

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A 61-year-old man was admitted to our hospital in April 18, 1988, with dyspnea and gingival bleeding. Physical examination revealed marked splenomegaly, and peripheral blood showed severe pancytopenia with 38% abnormal mononuclear cells. The abnormal cells were characterized by a hairy appearance under a phase contrast microscopy, and strong tartrate-resistant acid phosphatase activity. These cells reacted with CD19, CD25 and CD11c monoclonal antibodies by the immunostaining method. Bone marrow aspiration failed and bone marrow biopsy revealed diffuse proliferation of hairy cells (HC) with moderate fibrosis. In addition, the staining pattern of HC peroxidase is similar to that found in megakaryocyte series. He was diagnosed as HCL of the European-American type based on these findings. Interferon (IFN)-α was administered at a daily dosage of 3×10⁶ IU by intramuscular injection. Although splenomegaly and hematological conditions improved gradually, he received splenectomy because of his incomplete hematological improvement. Normalization of peripheral blood cell counts and a marked decrease of HC in bone marrow were obtained. Tubuloreticular structure and tubular confronting cisternae were seen in peripheral mononuclear cells during IFN therapy.

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The authors reported here a case of primary pulmonary amyloidosis, which developed into a localized form of primary macroglobulinemia (PMG) 10 years later. A nodular shadow was pointed out on routine chest x-ray films of a 61-year-old Japanese male in 1977. In 1981, a diagnosis of nodular primary pulmonary amyloidosis was made by percutaneous lung biopsy. At that time, he suffered from signs and symptoms of chronic cold agglutinin disease (CCAD). Cold agglutinins were IgM-kappa antibodies. In 1986, serum immunoelectrophoresis demonstrated the presence of a small amount of monoclonal IgM-kappa. In 1987, the patient was readmitted because of pleural effusions. In the pleural effusion, the IgM level was 3,341 mg/dl and the titer of cold agglutinin was 32,000. Cytological examinations of pleural effusion showed the proliferation of lymphocytes, lymphoid cells and plasma cells. These cells showed the monoclonality of IgM-kappa by the peroxidase-antiperoxidase method. At post-mortem examination in March 1988, PA and PMG were found, but both lesions were localized only in the thoracic cavity. It is suggested that primary amyloidosis (PA) as well as CCAD and monoclonal gammopathy of undetermined significance may be one of the pre-neoplastic conditions of PMG.

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We report a patient with systemic plasmacytosis with polyclonal hyperimmunoglobulinemia who at presentation showed a blood and bone marrow picture suggestive of plasma cell leukemia. A 78-year-old woman was admitted to our hospital because of marked hepatosplenomegaly and generalized lymphadenopathy. She had leukocytosis with 42% plasmacytes, and plasma cells were increased also in her bone marrow (32.6%). She had marked polyclonal hyperimmunoglobulinemia with increased IgG, IgA and IgE. IgM and IgD were normal. She complained of cough and dyspnea. Her general condition was too poor to remove a lymph node for pathological examination. After treatment with daunorubicin, vincristine and prednisolone (DVP), her lymphadenopathy diminished rapidly, the immunoglobulins decreased and the plasma cells in her blood disappeared. She achieved a complete remission and has been in good condition without further treatment for 24 months.

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Co-existence of three M-components in the serum or urine is rare. A case of non-Hodgkin's lymphoma was associated with three M-components. A 64-year-old woman was referred to our hospital because of M-proteinemia in June, 1989. On admission, serum electrophoresis on cellulose acetate membrane disclosed a triple M-peak. Immunoelectrophoresis showed M-bows for anti-IgG, anti-IgA, anti-IgM and anti-κ simultaneously. In the urine, κ type only Bence Jones protein was found. Scanning computed tomography revealed bulky masses in the lower abdomen, and the tumor masses were removed and diagnosed as non-Hodgkin's lymphoma. Immunohistochemial staining with antibodies to each immunoglobulins revealed the cells producing single M-component of each isotype of immunoglobulins. Although surgical removal of tumor caused a marked decrease in M-component especially IgAκ, consistent presence of plasmacytoid lymphocyte was observed in peripheral blood. Combination therapy with melphalan and procarbazine resulted in disappearance of IgGκ and IgAκ from the serum. In January 1990, she achieved partial remission and was discharged. The patient has remained in remission for 16 months.

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A autoimmune diseases complicated by malignant lymphoma have allvacted attention veceatly. studies in the international literature have demonstrated a significant complication of rheumatoid arthritis (RA) with malignant lymphoma. The authors report a case with a 15-year history of RA complicated with B cell lymphoma and gastrointestinal amyloidosis. A 66-year-old-woman was presented with easy fatigability and weight loss. with fever above 38°C (100°F). Clinical examination revealed marked abdominal tenderness and deformed joints of both hands and fingers. Rheumatid factor was weakly positive. A diagnosis of malignant lymphoma (follicular large, B cell type) was made by inguinal lymph node biopsy and endoscopic biopsy which revealed amyloid (AA type) deposition in the stomach and duodenum. The case showed a remarkable increase of a specific antibody titer against Epstein-Barr (EB) virus, which has been suggested to cause RA or lymphoma. The complications of the diseases in this case suggests a similar causative mechanism for the two different diseases.

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A 62-year-old man was admitted to our hospital because of generalized lymphadenopathy, fever and skin eruptions. The histology of the right cervical lymph nodes showed immunoblastic lymphadenopathy (IBL)-like T cell lymphoma. His laboratory data were as follows: hemoglobin concentration 7.1 g/dl, red blood cells 1,850,000/μl, reticulocytes 4.2%, total bilirubin 2.6mg/dl, direct bilirubin 0.5mg/dl, haptoglobin<10mg/dl, positive Coombs test. He was diagnosed as having IBL-like T cell lymphoma accompanied by autoimmune hemolytic anemia. He was succesfully treated with combination chemotherapy (Pro-MACE), and lymph node swelling and hemolytic anemia disappeared. He has been in complete remission for more than 1 year.

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A 10 month-old boy presented with fever. He was diagnosed as having acute myelomegakaryocytic leukemia by electron microscopic cytochemical examination. In spite of agressive chemotherapy, complete remission could not be achieved and he died seventeen months after the diagnosis was made. G-band karyotypes of the bone marrow cells revealed 45, XY, -17, -21, +dir tan dup (17;21) (17pter→cen→17q25::17q21→17q25;21q11→21qter). Furthermore, the same chromosomel aberrations were detected in the cells which were tetraploid and octaploid. Although, neoplastic changes in the progenitor cells immediately before differentiating to CFU-Meg and CFU-GM, are suggested there is a possibility of clonal evolution.

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Clinical efficacy of oral high-dose cepharanthin (40∼60 mg/day) was evaluated in nine patients with idiopathic thrombocytopenic purpura who were unable to discontinue the administration of adrenocorticosteroids or immunosuppressive drugs. Mean platelet counts significantly (p<0.05) rose from 4.5±0.9×10⁴/μl to 8.9±4.2×10⁴/μl without any side effects. Two to five months after the initiation of this therapy, 4 patients, including 3 who could discontinue adrenocorticosteroids, kept their platelet counts over 10×10⁴/μl. It was suggested that the oral administration of cepharanthin could be a beneficial and safe strategy for ITP.

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Twenty-two patients with steroid-unresponsive idiopathic thrombocytopenic purpura (ITP) were treated with cepharanthin, biscoclaurin alkaloid. Cepharanthin was administered orally at a daily dose of 40mg. Continuous elevation of platelet counts of 6.6∼15.0×10⁴/μl and 3∼5×10⁴/μl was attained in five and two patients, respectively, 1 to 4 months after the adminstration. Treatment with cepharanthin might be worth attempting in refractory ITP.

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