In a retrospective study to evaluate the efficacy of isoniazid (INH) for the prevention of tuberculosis, we studied 1760 patients with hematological malignancies over a twenty-year period (1970∼1989). 759 patients received oral INH, most of all received 400 mg per day. Only one (0.1%) of the patients receiving INH developed tuberculosis, whereas nine (0.9%) of the 1001 patients who did not recieve INH developed tuberculosis (p<0.05). We found that INH was very effective in the prevention of tuberculosis in patients with hematological malignancies, and was well tolerated.

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The phnomenon of EDTA-dependent pseudoleukocytopenia was observed in seven patients during the period from September 1989 to March 1990. The pseudo leukocytopenia was found to have come from aggregation of neutrophils. The aggregations were composed of neutrophils only, and did not include other granulocytes, monocytes and lymphocytes. The aggregations showed their maximum in size from 30 to 180 minutes after venipuncture at room temperature. The aggregated neutrophils were again dispersed by incubating at 37°C for 30 minutes. The degree of aggregation was found to be dependent on the concentration of EDTA. Neutrophil aggregation was not recognized in the blood films when sodium citrate or heprin was used as an anticoagulant. The results of mercaptoethanol agglutination test and immunocytochemical staining suggest that IgM antibody may play an important role in the formation of neutrophil aggregation. Four of the seven patients had suffered from hepatic disorder. However, the mechanism of EDTA-dependent neutrophil aggregation remains uncertain.

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The clinical effect of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was studied in 27 patients with childhood neutropenias. The sample consisted of 8 patients with congenital neutropenia (Kostmann type), 9 with neutropenia with miscellaneous causes (5 chronic benign, 2 associated with hypogammaglobulinemia, 1 drug-induced, and 1 hypoplastic type), 3 with cyclic neutropenia, and 7 with severe aplastic anemia. The rG-CSF was given subcutaneously (or in a few cases intravenously) at a dose of 2 μg/kg/day for 7 days and 5 μg/kg/day for additional 7 to 28 days in cases with poor response. The rG-CSF was effective in 18 of 27 cases (67%). Patients with congenital neutropenia and aplastic anemia responded less frequently and poorly. The mean level of absolute neutrophil counts of 8 congenital neutropenia cases increased from 88/μl to 2,718/μl. That of 9 miscellaneous cases changed from 189/μl to 7,224/μl at a dose of 2 μg/kg/day. In 7 aplastic anemia cases pretreatment level of 220/μl rose to 851/μl, usually after increasing the dose up to 5 μg/kg/day. The rG-CSF was apparently effective in 3 cases of cyclic neutropenia. In any type of neutropenia, the effect was largely transient; after the discontinuation of rG-CSF, the absolute neutrophil counts tended to decrease to pretreatment levels within 1 to 2 weeks. The G-CSF was well tolerated, and only one case with mild lumbago and another with minimal elevation of transaminases were observed. We conclude that the rG-CSF can be effective for treating various types of childhood neutropenia. For congenital neutropenia and aplastic anemia, larger doses and prolonged administration may be necessary.

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We administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 5 μg/kg/day by intravenous drip infusion for 21 consecutive days in autologous bone marrow transplanted patients. The period of posttransplant neutropenia was markedly shortend by the rhG-CSF treatment; mean days required for neutrophil recovery (>500/mm³) of 14.3 days in the rhG-CSF group (n=21) versus 27.8 days in the historical control group (n=11). More importantly, the numbers of febrile days between day 15 and day 28 were found to be fewer in the rG-CSF group than in control group. These effects were obtained without delay in the recovery of other blood cell series and without any side effect. We conclude that the posttransplant use of the rhG-CSF is beneficial for prevention and treatment of infectious complications after autologous bone marrow transplantation.

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A 46-year-old woman was admitted to our hospital because of hemorrhagic tendency. Normal coagulation test results conflicted with the diagnosis of disseminated intravascular coagulation (DIC). Furthermore, we saw no evidence of autoantibodies, including antinuclear antibodies and splenomegaly, and there was no past history of infection or medication. Peripheral blood test showed marked decrease of platelets only. Bone marrow aspiration revealed increased megakaryocytes. Morphology of other blood components was normal. Thus, we diagnosed this case as idiopathic thrombocytopenic purpura (ITP). Administration of prednisolone and an immunosppressants did not improve symptomes. So patient was temporarily discharged and treated with 6-MP at the outpatient department. She was rehospitalized for liver damage caused by the drug. Patient then developed sepsis from acinetobactor. We administered gabexate mesilate (FOY, 2,000 mg/day) for four days to prevent DIC. Platelet count, which was 1.5×10⁴/μl before FOT administration, began increasing on the second day, reaching 25.5×10⁴/μl on the fourth. Count rapidly decreased to 2.8×10⁴/μl on the seventh day after administration had been discontinued. Two-time FOY administration after patient's recovery from sepsis led to a definite, similar transient increase in platelet count. As ITP patients with transient increase in platelet count by FOY administration had not been reported, this case is thought to be an interesting case in the pathogenesis and treatment of ITP.

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A 63 year-old woman was referred to our hospital because of fever and increased number of blasts in the bone marrow. On physical examination she had slight hepatomegaly but no splenomegaly. Laboratory tests disclosed a hemoglobin level of 8.5 g/dl; a WBC count of 13,200/μl with 26% blasts; a platelet count of 51,000/μl. A bone marrow aspirate was normocellular with 74% blasts and 37% blasts were stained positive for myeloperoxidase. Cell surface markers for HLA-DR, CD10, CD19, CD13, CD33 were positive. Karyotype analysis revealed 46, XX, t(9q+;22q-) and 45XX, -7, t(9q+;22q-). Southern analysis showed rearrangement of immunoglobulin heavy chain but not T cell receptor β gene. Rearrangements in M-BCR were not detected with 5' or 3' bcr probes. After 2 courses of chemotherapy, blasts decreased to 7% with recovery of normal elements and 11 out of 20 metaphases of the bone marrow cells were normal karyotype. These findings suggest that this case was de novo Ph¹ positive acute leukemia which demonstrated both lymphoid and myeloid features.

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A 29-year-old male was diagnosed as having essential thrombocythemia (ET) in 1975. From that time, his platelet count gradually increased to more than 2×10⁶/μl until 1979. However, his platelet count gradually decreased to less than 6×10⁵/μl in 1985. Also, in 1982, erythroblasts and immature myeloid cells began to appear in the peripheral blood, and the liver and spleen became palpable in 1985. Bone marrow then revealed osteomyelosclerosis. These findings suggested that ET had transformed to myelofibrosis with myeloid metaplasia. Increased hepatosplenomegaly was accompanied by the appearance of ascites in June, 1988, and an esophageal varix ruptured in December of the same year. The varix was resected and the spleen was removed. After the operation, ascites did not recur and his condition became stable. Portal hypertension in this patient was considered to be due mainly to increased blood flow from the enlarged spleen.

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A 43 year-old man admitted to our hospital because of fever and splenomegaly. Laboratory findings were as follows: Hb 9.5 g/dl, Plts 4.9×10⁴/μl, LDH 2,348 IU/l. Bone marrow findings showed tumor cell 47% with or without phagocytosis. The tumor cells were stained positive lyzozyme and α₁ antitrypsin. Cytogenetic study was 47, XY, -7, -8, +9, -11, -12, -19, -21, 3q+, 6p+, +6 markers. This case was diagnosed as malignant histiocytosis. Complete remission was achieved with CHOP-E chemotherapy. Remission has been maintained with repeated this therapy. Etoposide deserves a good evalution in the treatment of malignant histiocytosis. Some cases of malignant histiocytosis with a t(2;5)(p23;q35) translocation were often reported in Europe and America, while there was no specific chromosomal abnormalities with malignant histiocytosis in Japan.

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A 15-y-o girl who had relapsed acute lymphoblastic leukemia, followed by the two-years complete remission, was treated with a reinduction chemotherapy including methotrexate, vincristine, L-asparaginase and dexamethasone (MOAD). During the chemotherapy, a remarkable hyperlipidemia has developed. The plasma levels of triglyceride and total cholesterol reached 14,450 mg/dl and 1,750 mg/dl, respectively. The laboratory data strongly suggest that L-asparaginase could induce this hyperlipidemia of Friedrickson type V. We could successfully reduce the levels of triglyceride and total cholesterol to the normal range by LDL-apheresis, and treat the patient with the chemotherapy excluding L-asparaginase to attain the second CR.

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A case of thrombotic thrombocytopenic purpura (TTP) associated with myasthenia gravis (MG) is reported. A 56-year-old woman was admitted to our hospital on April 27, 1988, because of easy fatigue and double vision. She was diagnosed as having myasthenia gravis from her neurological and laboratory findings. On the 14th hospital day, she developed fever, jaundice, hematuria, purpura and consciousness disturbance. Hematological examination revealed marked anemia, thrombocytopenia, fragmented red blood cells, elevated bilirubin and LDH level. Coagulation studies were almost normal. She was diagnosed as having TTP and treated with corticosteroid, antiplatelet agents and plasma exchange. Clinical condition and laboratory findings improved by the 23rd hospital day. It has been reported that TTP is associated with various autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrom or idiopathic thrombocytopenic purpura. However TTP associated with MG appears the first report. This case may suggest that one of pathogenesis of TTP is autoimmune mechanism.

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A patient with acute myelomegakaryocytic leukemia (AMMgL), which developed from myelodysplastic syndrome (MDS) after chemotherapy against complicated small cell lung cancer, is reported. The patient was a 66 year-old male, who first presented with moderate macrocytic anemia. Bone marrow aspiration showed absolute erythroid hypoplasia and morphological abnormalities were found in erythroid, granuloid and megakaryocytic lineage cells. Iron utilization studies using radioisotope showed ineffective hematopoiesis. He was diagnosed as having MDS (refractory anemia) and treated with prednisolone, fluoxymesterone, and transfusions. After 3 years, small cell lung cancer was found, but he achieved complete remission with chemotherapy. Since then, pancytopenia progressed with myelofibrosis. Abnormal blasts were found in peripheral blood and gradually increased. He finally died from a blastic crisis resulting in gastric bleeding. The blasts were peroxidase negative, platelet peroxidase postitive (10%), and glycoprotein II b/III a antibody positive, indicating megakaryoblasts.

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A 48-year-old woman was admitted in September 1987, because of lumbago and galactorrhea. Peripheral blood analysis showed neutrophilia and eosinophilia without abnormal lymphocytes. The antibody to adult T-cell leukemia (ATL) virus-associated antigen was detected and a hyperprolactinemia was observed. The blastogenic responses to PHA, ConA and PWM were lowered. Brain CT and MRI scannings showed no abnormalities in the hypophysis and hypothalamus, but abdomen CT revealed markedly enlarged abdominal lymph nodes. Two months after the administration of OK432 and PSK, the lymph node swellings disappeared and the responses to PHA, ConA and PWM were normalized, but hyperprolactinemia and galactorrhea persisted. After four months of the remission period, the patient developed lymph node swellings again, and was diagnosed from the biopsy specimen of the retroperitoneal lymph node as having malignant lymphoma of diffuse mixed cell type. Southern blot analysis showed a monoclonal integration of HTLV-I proviral DNA. Despite repeated combination chemotherapies, she died of pneumonia in February 1989. Autopsy revealed marked infiltrations of lymphoma cells in the liver, spleen and lungs, but no abnormality accounting for hyperprolactinemia was detected in the suprasellar regions. This case was of interest in that immunotherapy was effective in achieving a remission and in normalizing immuno-paramaters in ATLL.

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A 16-year-old male with acute myelogenous leukemia (M1) presented with fulminant hepatitis (massive hepatic necrosis). He achieved a complete remission with the administration of AdVP (doxorubicin, vincristine and prednisolone), and thereafter received consolidation or intensification therapy 5 times in combination with AdVP plus enocitabine. A bone marrow examination carried out before the 6th round of chemotherapy revealed a slight increase of myeloblast (7%). L-AdVP (including l-asparaginase in addition to AdVP) was administered with a good result. However, 13 days after the end of the therapy he complained of acute abdominal pain, headache and fever. The following day, his consciousness level became lower and severe jaundice appeared. The serum transaminase level highly elevated with PT and aPTT severely elongated. He was diagnosed as having fulminant hepatitis. Elevation of the titer of IgM-HBc suggested that the fulminant hepatitis was attributed to HBV, which was probably transmitted by blood transfusion done in the first induction therapy and stayed latent during immunosuppressive chemotherapy. After receiving 10 sessions of plasma exchange (3.2 l/day), he recovered, free from any major complications except posttransfusion hepatitis. In his serum taken at 1 month after the recovery of posttransfusion hepatitis, HCV (Chiron) antibody was detected. There have been few reports concerning fulminant hepatitis associated with acute leukemia. In this case, plasma exchange was very effective in treating fulminant hepatitis.

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Percentage of RNA-rich (High Fluorescence Ratio, HFR), RNA-middle (Middle Fluorescence Ratio, MFR) and RNA-low (Low Fluorescence Ratio, LFR) reticulocytes was estimated by Sysmex R-1000 retculocyte counter during the chemotherapy of 27 cases with acute leukemia and malignant lymphoma (36 courses). In the beginning of marrow suppression, HFR and/or MFR were decreased faster than LFR, neutrophils or platelets in 14 courses (38.9%). Simultaneous decrease of HFR, MFR and other blood cells were observed in 57.2%. In the recovery phase of bone marrow, faster increase of HFR and/or MFR was noted in 52.8% and simultaneous increase of these reticulocytes with other blood cells was observed in 9 courses (25%). Appearance rate of RNA-rich younger reticulocytes is a sensitive parameter for the prediction of bone marrow suppression and recovery during the chemotherapy for hematologic malignancy.

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VAD regimen, combining vincristine, doxorubicin, and dexamethasone was given to 6 previously untreated and 4 treated patients with multiple myeloma. The response rate was obtained in 67% of previously untreated patients and in 50% of previously treated patients. In responders, a rapid improvement of clinical symptoms accompanied with a significant decrease in M-protein was observed. Patients with response to VAD therapy were received melphalan and prednisolone as maintenance. Response duration ranged between 4 months and 38 months. The infectious episodes were occurred in 36.8% patients but none of these was serious. The present results suggest that VAD regimen is useful as primary treatment for multiple myeloma when rapid control of disease is necessary.

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