A review of the literature was performed in an attempt to delineate the features of chronic neutrophilic leukemia (CNL). CNL is a very rare type of leukemia and only about 50 cases have been diagnosed with certainty in the literature. The diagnostic criteria of CNL are proposed, that is, 1) severe sustained mature neutrophilic leukocytosis (<20×10⁹/l ), 2) the absence of Ph¹ chromosome, 3) the absence of other chronic myeloproliferative disorders (polycythemia vera and essential thrombocythemia), 4) high neutrophilic alkaline phosphatase, and 5) the absence of a reactive leukemoid state. All these items have to be fulfilled for the diagnosis. Hepatosplenomegaly, Döhle bodies and toxic granules in neutrophils, elevated vitamin B₁₂, lysozyme and uric acid in the serum are virtually common findings, but not essential.
The coexistence of CNL and monoclonal gammopathy including myeloma appears substantial.

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Chronic lymphocytic leukemia (CLL) is very rare in Japan, in comparison with the prevalance of CLL in the United States of America and Europe.
Moreover, it has been reported that isotype of surface-membrane immunoglobulin (Sm-Ig) of CLL cells is different, characterized by the high incidence of IgG isotype or Sm-Ig^- in Japan.
In this series, Sm-Ig and surface antigens of peripheral mononuclear cells from Japanese CLL patients were analysed by a laser flow cytometry system (Spectrum III/Ortho Diagnostic System).
Monoclonal Sm-Ig was identified in 15 of 18; 6 of the 15 patients bore IgM isotype, 7 bore IgM and IgD isotype and 2 bore IgG isotype. The ratio of the kappa to lambda light chain type of Sm-Ig was 6 to 9 in our series. These Sm-IgM with or without IgD were faintly stained.
Cells from 9 CLL patients reacted with the monoclonal antibodies anti-Leu-1, anti-B1, anti-B2, anti-B7 and anti-HLA-DR and unreacted with monoclonal antibodies anti-Leu-2a, anti-Leu-3a and anti-IL2-R.
The data obtained in these cases are in agreement with the experience of other investigators in the USA and Europe.
Therefore, it is clarified that cell surface characterization of Japanese CLL cells is not different from that of European and American cases.

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Eighteen patients with malignant lymphoma were treated with a combination chemotherapy regimen consisting of mitoxantrone cyclophosphamide vincristine prednisolone (MCOP). Six patients achieved complete remission and eight partial remission. Good responses were obtained in all patients (four complete remission, two partial remission) who were treated by this regimen as a first chemotherapy. The side effects experienced by all patients on MCOP therapy were leukocytopenia and gastrointestinal toxicity. Cardiac toxicity was not encountered. The results suggest that MCOP therapy is an effective combination chemotherapy regimen for treatments of malignant lymphoma.

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Cooperative study on the evaluation of clinical effects of a cephamycin antibiotic cefmetazole (CMZ) was performed in patients with various infections accompanying granulocytopenia in hematological disorders in 13 institutions. CMZ (2 to 9 g/day) was administered intravenously by drip infusion divided in 2 to 4 doses. Efficacy of CMZ was evaluated according to the criteria of Takaku et al. Two hundred and fourteen cases were entered to this study, and 121 cases were suitable for evaluation. Infections consisted of sepsis, pneumonia, respiratory tract infections, and so on. More than half of the patients had acute leukemia, and about 90% of them were hematological malignancies. When only CMZ was administered, the efficacy was 53.2%, and when CMZ was added to the previous treatment, the efficacy was 58.8%. The overall efficacy of CMZ was 52.1%. Adverse reactions were minimal, and disappeared immediately after taking off the administration.

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Cytogenetic studies were performed on the bone marrow (BM) cells obtained from 12 patients with essential thrombocythemia (ET). Two of them had chromosome abnormalities. One patient showed a mosaic of two karyotypes of 46, XY and 46, XY, -15, del (6) (q25), +der (15) t (15; ?) (q26; ?). This abnormal karyotype was observed in half of the checked BM metaphases. The other patient showed only one karyotype of 46, XY, del (20) (q11) in the BM. In both of patients, chromosomal analyses on the cultured peripheral blood cells with phythohemagglutinin (PHA) for 72 hrs were carried out and all metaphases observed were normal male karyotypes. The frequency of polyploid cells was less than 1% in all cases except one with 3.3%. No relationship between cytogenetic findings and clinical manifestations or results of another clinical examinations was observed.

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In this paper the therapeutic effects on 51 patients with hypoplastic leukemia were analyzed in order to establish the optimal clinical management of hypoplastic leukemia. Among 44 patients, hospitalized before 1984, 27 patients were treated with blood transfusion and/or single antileukemic agent, and 17 patients treated with combination chemotherapeutic regimens. As results, only 8, of which 7 patients were received combination chemotherapy, obtained CR and ages of responders were all below 65 years old. On the other hand, among 7 patients treated with low dose behenoyl cytosine arabinoside (LD-BHAC) therapy, applied since 1984, 3 patients obtained CR and 2 patients obtained PR. Responders were aged over 65 years old. Although hematologic toxicities were found during LD-BHAC therapy, they were all controllable. As conclusion, LD-BHAC therapy is thought to be a promising remission induction chemotherapy for aged patients with hypoplastic leukemia.

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Progressive multifocal leukoencephalopathy (PML) developed in a 4-year-old boy with acute lymphocytic leukemia. Papova virus (SV40 like virus) was isolated from his cerebrospinal fluid. The antibody titer to the isolated virus was 1:640 in serum and 1:16 in cerebrospinal fluid.
Brain CT scan showed multifocal low density in the white matter. the progressive neurologic illness in this patient was characterized by spastic palsy, ataxia, intellectual deterioration, seizure, and coma.
An important element in the pathogenesis of PML is the presence of diseases that have impaired host resistance. As one of CNS complicatiosn of ALL, we need to take notice of the papova virus infections.

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A 51-year-old male was admitted because of muscle weakness and paresthesia of extremities. The eruptions with itching and pigmentation were recognized on his face and back. A cerebrospinal fluid examination revealed protein-cell dissociation, peripheral nerve verocity was delayed, and neurological investigations revealed polyneuropathy of glove and stocking type. A bone marrow aspiration showed slight proliferation of plasma cells. Decreased testslerone and increased FSH were pointed out by endocrinological analysis. A right subclavian lymphnode biopsy revealed a proliferation of plasma cells of germinal center, and a diagnosis of Crow-Fukase syndrome was made. We started a therapy with prednisolone and melphalan, but periodic fever and severe thrombocytopenia occurred. Infections and side effects of drugs were denied. So we suspected these symptoms had a relation to Crow-Fukase syndrome and VENP therapy was started. A temporary remission was obtained. But he died of respiratory distress after several recurrence of these symptoms.

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A 60-year-old male was admitted to the hospital. He had been well untill two months before admission, when the rash on the anterior chest was found and a diagnosis of lymphoplasmacytoid lymphoma was established by biopsy. One day before admission he experienced high fever and severe low back pain. The white cell count was 700/mm³ with a few atypical cells. Bone marrow picture showed the atypical cells of 96%, a clinical diagnosis of multiple myeloma was made and treatment with prednisolone, 40mg/day, and melphalan, 2mg/day, was begun. Five days later, most rasheds disappeared but the amount of urine diminished and the blood urea nitrogen (BUN) was 99.7mg/dl, creatinine 4.8mg/dl, potassium 5.3 mEq/L, uric acid 13.6mg/dl, phospholus 8.0mg/dl, lactec dehydrogenase ((LDH) 32,100 U/L; a diagnosis of acute tumor lysis syndrome was made. Hemodialysis was carried out, but an association of disseminated intravascular coagulation (DIC), congestive heart failure, and interstitial pneumonia led to a death on the 21st hospital day. From the histochemical characteristics of atypical cells, a final diagnosis was acute monocytic leukemia with tumor formation. Few cases of acute monocytic leukemia has been reported as an underlying cause of acute tumor lysis syndrome, and its induction by small dose of chemothrapy, complicated by DIC and by interstitial pneumonia has been rerely experienced.

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A case of sinus histiocytosis with massive lymphadenopathy is reported. A Japanese woman noticed gingival swelling when she was 27 years old. One year later, nasal obstruction and swelling of right cervical lymph node developed. Lymph node biopsy showed pericapsular fibrosis, dilatation of sinus, plasma cell infiltration in medullary cords, and marked increase in large histiocytes in sinuses and paracortical areas. Enlarged histiocytes were S-100 protein-positive and muramidase-negative, and engulfed not only lymphocytes but also plasma cells, neutrophils, and muramidase-positive monocytes. Laboratory data showed lymphocytopenia, hypergammaglobulinemia, and elevated erythrocyte sedimentation rate. She was treated with antibiotics, prednisolone, OK432, and irradiation without beneficial effects. Although sinus histiocytosis with massive lymphadenopathy involved cervical, axillary, and inguinal lymph nodes and nasal cavity in this patient, her symptoms and signs subsided spontaneously after 89 months from the onset of lymphadenopathy.

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A 57-year-old male was admitted to our department because of palpitation, shortness of breath and pancytopenia on June 18, 1985. On admission, conjunctiva was anemic, and petechiae and ecchymoses were found in the skin. Laboratory findings revealed pancytopenia, a reticulocyte count of 24‰, positive Ham's test, NAP score of 68, red cell acetylcholine esterase of 0.8 U, hemosiderinuria, LDH 842 WrU, and haptoglobin less than 10mg/dl. Bone marrow showed hypocellularity (0.85×10⁴/cmm). Diagnosis of PNH with hypoplastic bone marrow was made. Although treatment consisting of anabolic steroids and prednisolone was not effective, LDH activity was decreased during the clinical course. To evaluate the abnormal complement sensitive cells (PNH III cells) in the patient, complement lysis sensitivity test was repeated during the clinical course. The result indicated disappearance of the abnormal red cell populations and a change in the sensitivity to complement.
In early January 1986, the patient suffered from anal abscess, and died of cerebral hemorrhage on Febrary 16, 1986.

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A 55-year-old man was admitted to our hospital with bleeding tendency. A diagnosis of ATL (Adult T-cell Leukemia) was made, and we achieved complete remission with VEPA therapy. But after two months or so, the disease relapsed, and he died of intra-cranial bleeding. The surface marker of the leukemic cell changed OKT-4 positive and OKT-8 negative into OKT-4 positive and OKT-8 positive during his clinical course.
A ATL cell is considered to be a mature thymocyte, but the leukemic cell in this case was considered to be a common thymocyte.

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A 25-year-old female was admitted to a hospital with low grade fever and jaundice on Feb. 22, 1984. A diangosis of acute hepatitis type B was made from the biochemical findings of markedly elevated serum transaminase and positive HBsAg.
But she was referred to our hospital with hyperbililubinemia on March 13, and she developed severe anemia and reticulocytosis from 5th hospital day. A bone marrow aspirate showed hyperplasia of erythroblasts. The level of LDH increased and haptoglobin decreased, but Coombs test was negative. She was diagnosed as hemolytic anemia associated with viral hepatitis and responded excellently to the treatment with high dose prednisolone. Liver function improved thereafter and HBsAg turned to be negative.

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A case of chronic adult T-cell leukemia (ATL) with T4 and T8 positive leukemic cells associated with central diabetes insipidus was reported.
A 39-year-old man was admitted to the hospital because of left pleural effusion in February 1981. Pleural effusion and peripheral blood revealed atypical lymphocytes with convoluted nuclei. A diagnosis of leukemic T-cell malignant lymphoma was made. Pleural effusion was improved by VEP-therapy but examination of blood smear showed constantly 10∼20% atypical lymphpcytes. He was re-admitted because of general fatigue, shortness of breath, polydipsia and polyuria. Chest X-ray showed pleural effusion. The leukocyte count in peripheral blood was 30,900/cmm with 46.5% atypical lymphocytes. The examination of leukemic cell surface markers showed OKT3 37.6%, OKT4 70.7%, OK8 60.7%, OKT11 87% in peripheral blood: OKT3 20.9%, OKT4 81.4%, OKT8 78.8%, OKT 11 94.9% in pleural effusion, indicating that the ATL cells of this patient have both T4 and T8 antigens. The diagnosis of ATL with T4 and T8 was made, because anti-ATLA (adult T-cell leukemia associated antigen) antibody was positive and the integration of HTLV-I (human T-cell lymphotropic virus-I) in the DNA of the leukemic cells was demonstrated.
Urine volume was about 5 litter daily and specific gravity was 1.006. Vasopressin test was positive. Dehydration test and Carter-Robbins test established the diagnosis of central diabetes insipidus. Skull X-ray and brain CT showed normal appearance, and the levels of other pituitary hormones were normal. Diabetes insipidus was treated by 1-deamino-8-arginine vasopressin (DDAVP) and the therapy was effective.

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A case of chronic myelomonocytic leukemia (CMMoL) which was successfully treated with low dose Ara-C is reported.
A 64-years-old male was admitted with subcutaneous bleeding on March 31, 1982. Although the WBC count and percentage of monocytes in peripheral blood were high, 20,600/cmm and 32% respectively, RBC and PLT counts were normal. A bone marrow aspirate revealed a hypercellular material (NCC 32×10⁴/cmm) with granulocytic and monocytic hyperplasia. The lysozyme was increased in serum and urine, and the patient was diagnosed as CMMoL.
Thereafter, he was treated only with some hemostatic drugs as an outpatient for approximately 2 years. On July 2, 1984, he was re-admitted with massive subcutaneous bleeding and marked hepatosplenomegaly. After the re-admission, skin eruptions were also increased and diagnosed as leukemia cutis by a biopsy. Leukemia cutis was disappeared and hepatosplenomegaly was remarkably decreased in size after subcutaneous injections of low dose Ara-C (14mg×2/day) for 14 days.
While the standard protbcol for CMMoL treatment has not been decided yet, the low dose Ara-C therapy was recommended as an useful treatment to CMMoL from our experimental study.

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A 65-year-old woman was admitted to our hospital because of a forehead mass appearing at a site of previous trauma. Pathological examination of the mass revealed diffuse lymphoma, mixed cell type (LSG classification). There was no sign of lymphadenopathy. Her WBC was 6,500/μl with no abnormal lymphocytes. Gallium-scan showed high activity only at the forehead. Head-CT showed a contrast-enhanced large soft tissue mass on both sides of the bone with very little change of the bone itself. Abdominal-CT and lymphangiography revealed no evidence of systemic lymphoma.
She was treated with irradiation (5,000R) to the soft tissue mass on both sides of the bone. Resolution of the mass was successfully obtained. After completion of irradiation therapy right periauricular and axillary lymphadenopathy developed, and multiple areas of high activity was observed in the abdomen by gallium-scan. Spinal fluid was normal in appearance. Right periauricular lymph node biopsy revealed diffuse lymphoma, mixed cell type. Immunological phenotyping of the neoplastic lymphocytes revealed Ig G-k.
The patient achieved complete remission after administration of vincristine, Endoxan, and Adriacin. After consolidation by identical schedule, complete remission has been maintained up to the time of writing (12+ months).

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A 22-year-old man was admitted because of low grade fever and general fatigue. Anemia, elevated ESR and polyclonal hyperimmunoglobulinemia were observed. There were hepatosplenomegaly and a 6×4cm mass on the left of umbilicus. A ⁶⁷Ga scan showed abnormal uptake on the left side between third lumber vertebra and fourth one. Exploratory laparotomy was performed and several masses, each of which were nut or knuckle in size, were found in the mesentery beside Treitz's ligament. One of them was resected. Pathologically, the mass was a lymphnode composed of follicular hyperplasia and prominent sheets of mature plasma cell ploliferation in interfollicular areas. The presence of polyclonal immunoglobulins in the cytoplasma of plasma cells in the resected lymphnode were demonstrated by the peroxidase-antiperoxidase method. He was treated with ⁶⁰Co and received 4,000 rads to a restricted port involving residual masses. Then clinical symptoms and labolatory data were improved gradually. Residual masses were resected by reoperation because of no remarkable decrease in size of them. Pathologically. there is no remarkable change between before and after radiation therapy. Radiation therapy may control the activity of proliferative cells, so in cases where complete removal of the lesion is impossible, radiation therapy is worth a trial.

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A 49-year-old woman was admitted in May, 1984 because of severe lumbago. A diagnosis of nonsecretory myeloma (BJ-λ) was made, based on the presence of multiple osteolytic lesions as well as bone marrow plasmocytosis with intracytoplasmic immunoglobulins of a monoclonal BJ-λ type but on the absence of detectable monoclonal immuno-globulins in either serum or urine. After chemotherapy with cyclophosphamide, the patient was improved. In July 1985, a relapse associated with pleural effusions and hypercalcemia occurred. Abnormal cells in pleural effusions had been proved to be plasma cells micro- as well as electron-microscopically. These cells were positive for OKT10 and PCA-1 and contained intracytoplasmic λ light chains. A cytogenetical analysis was performed on myeloma cells in pleural effusion. A total of 27 metaphase cells was analized. A chromosomal abnormality of t (14; 18) (q32; q21) was observed consistently. In addition, t (1; 7), t (2; 7), del (16) (q11), i (16q) and t (11; 20) were found in almost all the metaphases examined.
A 14q+ marker chromosome derived from t (14; 18) (q32; q21) has been considered to be relatively specific to follicular lymphoma and diffuse lymphoma. However, its occurrence has not been reported in plasma cell dyscrasia.

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Three cases coexisted with acute nonlymphocytic leukemia and gastric cancer are reported.
Subclasses of leukemia were M1, M5, both with hypoplastic bone marrow, and M3 respectively. All of them were advanced ages. Two cases were diagnosed by gastroendoscopy but one case failed to detect coexistene of gastric cancer before autopsy. Our cases and summary of literaturs suggest there may be increasing coexistences of gastric cancer in patients with acute leukemia in old ages. Proper examinations, especially gastrointestinal-fiberscopy, shoud be considered in leukemia patients with prolonged gastrointestinal symptoms such as G.I. bleeding or epigastric fullness.

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Hemopoietic dysplasia in childhood is different from myelodysplastic syndrome in adults. A number of atypical cases that could not be categorized to the any classical entity have been registrated to the Study Group of Hemopoietic Disorders sponso ed by Ministry of Health and Welfare. In this paper, we presented 5 children with aplastic anemia who showed prodromal course of pre-aplastic state. Case 1: A six-year-old boy was presented with pancytopenia accompanied with normocellular marrow. The bone marrow smear revealed the increase of atypical dense granulated promyelocytes. After the treatment with vincristine and prednisolone, the patient had been in hematological remission for 3 years and 9 months, maintained with 6MP. Immediately after the discontinuation of 6MP, he developed pancytopenia with hypocellular marrow. At this time there was no increase of the atypical cells. The pancytopenia has been persisted for 3 years thereafter. Case 2: A four-year-old girl was presented with thrombocytopenia and neutropenia with normocellular marrow. Morphological abnormalities in erythroid and myeloid cells were observed. She was treated with meptiostane under the diagnosis of pre-aplastic state and the anemia was improved. Following the cessation of the therapy, however, the patient showed typical clinical manifestation of aplastic anemia. Case 3: A six-year-old girl was presented with thrombocytopenia but not anemia. Her marrow cellularity was diverse and megakaryocytes were decreased. Her clinical course has been followed without treatment. Case 4: A six year-old girl was presented with thrombocytopenia accompanied with normocellular marrow. She was treated with prednisolone under the diagnosis of chronic idiopathic thrombocytopenic purpura. Four months later, she developed typical aplastic anemia. Case 5: A four-year-old boy was presented with anemia and thrombocytopenia accompanied with hypocellular marrow. His peripheral leukocyte and neutrophil counts were normal. There were internuclear chromatin bridge of the erythroblasts and hypersegmentation of the myeloid cells. To confirm diagnosis of atypical cases, comprehensive assessment including analysis of ferrokinetics, hemopoietic stem cell culture and bone marrow biopsy were important and helpful. We suggest that there are some cases with features of hemopoietic dysplasia that may eventually develop aplastic anemia in childhood.

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A patient, 50-year-old female, developed cerebellar infarction following remission induction therapy for acute lymphoblastic leukemia. The therapy consisted of L-asparaginase, vincristine, aclarubicin and prednisolone. The concentration of protein C, antithrombin III, plasminogen and fibrinogen in the plasma taken from the patientb efore, during and after starting the chemotherapy were assayed retrospectively. Fibrinogen concentration rapidly decreased to 19% of its normal mean value on the day before developing cerebellar infarction. Protein C, antithrombin III and plasminogen also declined to 40%, 43%, and 35%, respectively, of their normal mean value.
The cerebellar infarction in the present case may be explained by this complex set of abnormalities in the coagulation and fibrinolytic system.

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A 28-year-old male was admitted because of cough and discomfort of chest in December, 1984. He was diagnosed as ALL (pre-Tcell type) from findings of bone marrow aspirate and peripheral blood. On admission pleural effusion was found on chest x-ray film. Immature cells with same morphological features to those in marrow smear were found in the pleural exsudate aspirated. Pleural effusion became reduced by AVP therapy, although 60% of bone marrow cells were still leukemic blasts. On January 29, 1985 pleural effusion increased again with pericardial effusion which had similar characteristics to the pleural effussion. These effusion rapidly disappeared and complete remission was achieved by DLVP therapy. After 20,00 rad of cranial irradiation with intrathecal MTX and 2 courses of consolidation chemotherapy by DVLP regimen, he was discharged from the hospital. As of March 28, he is still in remission under maintenance chemotherapy (6MP/Ara C).

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Acute myeloblastic leukemia associated with double minute chromosomes (DMS) is reported. This patient, diagnosed as M2 according to French-American-British (FAB) classification, showed DMS in bone marrow aspirates before any chemotherapy. Karyotypes was as follows: 44, XX, -8, -9, -17, +der (8) t (8; 17) (q13; q11.2). It is thought that DMS derived their origin from leukemic cells, because, during partial remission, they disappeared and abnormal karyotype was not found. After short time of partial remission, she relapsed as monocytic appearance with the increase of lysozyme. The number of DMS per cell decreased and that of chromosome was ranged between hypodiploid and hypotetraploid, associated with additional abnormalities, including 2p-, 5p+ and the other marker chromosome. The presence of DMS is generally thought to indicate poor prognosis, but the number of DMS per cell did not parallel to the increase of leukemic cells. Therefore, it follows that the karyotypic abnormalities play a great role in prognosis, besides the number of DMS.

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