The pattern of relapse from complete remission of advanced non-Hodgkin's lymphoma is discussed.
Forty-seven patients, referred between 1976 and 1983, were treated by combination chemotherapy consisting of vincristine, cyclophosphamide and prednisolone (VCP). Twenty-two patients who were resistant to VCP therapy or who relapsed from complete remission by VCP therapy were treated with a combination of adriamycin, bleomycin and prednisolone (ABP therapy). Among the forty-seven patients, twenty-four relapsed, mostly within 1 year, especially within 6 months. The sites of relapse were the same as the initial involvement in most cases.

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The relation between the FAB classification and presenting clinical features was studied in 106 patients over 15 years of age with acute nonlymphocytic leukemia. Leukemic infiltrations of the liver, lymph nodes, skin, gums and central nervous system were seen extremely in patients with monoblastic subgroups (M5a, M5b). In patients with M5, peripheral leukocyte and blast cell counts were higher than in those with M2 and M3, but not significantly different in those with M1. Peripheral granulocyte and lymphocyte counts were higher in M5 than in myeloblastic subgroups (M1, M2, M3). Polyclonal hypergammaglobulinemia was recognized in monoblastic subgroups, and IgG, IgA and IgM were significantly increased compared to myeloblastic subgroups. These findings were unique clinical features in monoblastic subgroups and may relate monocytic functions. On the other hand, patients over 60 years of age with M5 had a complete remission rate of 14 percent compared to 88 percent for those under 60 years of age.

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The acidified glycerol lysis test (AGLT) has been recently used for the diagnosis of hereditary spherocytosis (HS) as a screening test. This test became occasionally false positive when the results were analyzed by AGLT₅₀ (time required for the optical density to fall to half of the initial value after the glycerol reagent added). We have devised a new analyzing method, AGLT₁₀ (time required for the optical density to fall to 10% of the initial value) and ΔOD/min (decrement of a variable optical density for one minute after an adding glycerol reagent). This modified AGLT was applied to the patients with HS, 56 patients with various hematological disorders, and 10 normal subjects. At the diagnosis of HS, the AGLT₁₀ and ΔOD/min offered more accurate rather than the AGLT₅₀. Since ΔOD/min showed a significant correlation with the osmotic fragility test, ΔOD/min would be able to use one of the screening tests for the HS. This test was more simple, and rapid for the diagnosis of HS than ordinary osmotic fragility test. We experienced one case in a HS family with negative osmotic fragility test in spite of the obvious hemolysis. This case showed a typical HS pattern in AGLT₁₀ and ΔOD/min. In this paper, we discussed the clinical usefulness of this modified AGLT for the diagnosis of HS.

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Glucose-6-Phosphatase (G-6-Pase) which catalizes both the synthesis and hydrolysis of glucose-6-phosphate, is biochemically demonstrable in the nuclear membrane and endoplasmic reticulum (ER). We have demonstrated ultrastructurally the G-6-Pase activity in bone marrow cells from 53 cases of patients. The erythroblasts were studied in 24 of 53 cases, whose bone marrow was normo- or hypercellular and contained erythroblasts above 10% by analysis. The reaction products, specifically indicating the sites of G-6-Pase activity, were observed in the perinuclear space and in the saccules of ER of proerythroblasts, but they were not observed in normal erythroblasts. In the erythroblasts from patients with diseases, such as erythroleukemia, refractory anemia, etc., in which abnormalities of erythroid cells were present, the reaction products were observed. In the presence of ultrastructural G-6-Pase activity, positive erythroblasts have a certain relation to the presence of PAS reaction positive erythroblasts. As mentioned above, the demonstration of G-6-Pase activity in erythroblasts is useful for detecting abnormal erythroblasts. Since the activities were detected in proerythroblasts, the ultrstructural demonstration of G-6-Pase activity may serve as a marker indicating a maturational stage of erythroblasts.

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We analysed clinical features of 28 adult patients with moderate or severe aplastic anemia and proposed new criteria for the selection of patients with “true” severe aplastic anemia.
The number of granulocytes, reticulocytes, and platelets in the peripheral blood and the frequency of hemopoietic cells in the bone marrow at the diagnosis of aplastic anemia were evaluated as prognostic parameters; each of the following parameters of granulocytes≥250/cmm, reticulocytes≥10,000/cmm, platelets≥7,500/cmm, and hemopoietic cells in the bone marrow≥25% was calculated as 1 point. Each of the following ranges of reticulocytes 5,000 to 9,999/cmm, platelets 2,500 to 7,499/cmm, and hemopoietic cells 10 to 24.9% was calculated as 0.5 points, and the remaining values in these cells were calculated as 0 point. Patients having 0 point had extremely poor prognosis. On the other hand, all patients having 4 points survived for more than 2 years. Our results suggest that bone marrow transplantation may not be the best therapy for the patients having 3 or more points.

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A number of methods have been developed to measure platelet-associated IgG (PA-IgG), however, the methods are either not sensitive or complex for general use. We have therefore established a new method of fluorescent PA-IgG assay.
The present method is based on the treatment of platelets with neuraminidase and the PA-IgG positive rate (%PA-IgG) obtained from the results of treated and non-treated platelets.
The value of PA-IgG in treated and non-treated platelets in normal controls was found to be 1.5±1.3% and 1.3±1.1% respectively. In patients with thrombocytopenia (ITP, SLE, addisonian anemia, acute leute leukemic patients who received platelet concentrates from random donors), the value of PA-IgG in treated and non-treated platelets was 4.6∼72% and 0.7∼25%. The results indicated that the value of PA-IgG was significantly elevated by neuraminidase treatment of platelets. And in patients, platelet count correlated inversely with the percent value of PA-IgG in neuraminidase treatment when the platelet conut was less than 4×10⁴/μl.
There was also close relashionship between the value of PA-IgG and clinical course in two patients with acute ITP and in one acute leukemic patient who received platelet concentrates from random donors.
And mechanisms involing sialic acid on platelet membrane in association with PA-IgG were discussed.
Our finding would suggest that this new method is useful in understanding conditions of patients with thrombocytopenia.

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A 14-year-old patient with acute nonlymphocytic leukemia became refractory to random platelets after frequent transfusions of multiple donor platelet concentrates. Lymphocyte toxic antibody was measured in the patient using NIH-LCT and the antiglobulin test for lymphocyte toxicity. A specific HLA-Bw4 antibody was demonstrated in her serum. PSIFT and β-thromboglobulin release test showed antibody against platelets from donors with HLA-Bw4 antigen. The patient had markedly poor post transfusion platelet recoveries following Bw4/Bw6 incompatible transfusion. In contrast, a mean 1 hour-post transfusion platelet recovery was at least 50% in 2 of 3 donors homozygous for Bw6. The clinical significance of Bw4 antibody is discussed.

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Clinical effects and pharmacokinetics of HDCA (3 g/m² vs 1.5 g/m²) in the treatment of refractory leukemia and non-Hodgkin's lymphoma (NHL) were studied. Six patients with refractory leukemia (hematological or CNS relapse) were treated for remission induction and three patients with NHL for consolidation. Patients' ages ranged from 6 to 14 yrs. 3 g/m² of cytosine arabinoside (CA) was administered every 12 hours for 2 or 6 days (regimen A) and 1.5 g/m² of CA every 12 hours for 6 days (regimen B). In both methods, 18 courses were performed. ALL patients except one who was on regimen A responded well and showed clinical improvents. Toxicity of HDCA was generally tolerable. However high frequency of severe infections such as bacterial (2 occasions) and fugal (4 occasions) were observed.
The mean plasma levels of CA on regimen A and B were 21 μg/ml and 16 μg/ml, respectively. CSF level of CA was about 5% of plasma level and therapeutic level (over 0.1μg/ml) was obtained in both regimens.

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Tetraploid chromosome abnormality including 4q+ in a 10 years-old girl with non-Hodgkin's lymphoma is reported. She was admitted to Saitama Children's Medical Center presenting with fever and cervical lymphadenopathy in September, 1984. She was diagnosed as having diffuse lymphoma, large cell type, according to the LSG classification on her biopsied specimen done at her right cervical lymphnode in November. Clinical and laboratory findings revealed that she was in stage III. Chemotherapy was started and she has been in complete remission for 5 months. Surface marker analysis of the biopsied lymphnode cells showed B-cell precursor cell character. Chromosomal analysis of those showed that representative karyotype was 92, XXXX, -4, -4, +2der (4) t (1; 4) (q21; q35).
The lymphoma cells with tetraploidy were assumed to be larger in size than those with diploidy. Tetraploidy in childhood non-Hodgkin's lymphoma has been rarely reported so far, thus relation between prognosis and tetraploidy remains to be elucidated.

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A 55-year-old man, who had been diagnosed as the hypereosinophilic syndrome presenting persisting eosinophilia for 4 years (>3,000/μl) of unknown origin and eosinophilic infiltration of the gastrointestinal mucosa, was admitted because of the appearance of blastoid cells (7%) with monocytosis (64%) in the peripheral blood. Bone marrow study revealed a marked proliferation of α-naphthyl-acetate-esterase positive monoblasts (80.6%) without an increase of eosinophils. A dignosis of acute monoblastic leukemia preceded by the hypereosinophilic syndrome was made.
Bone marrow cells from the patient were cultured with various inducers of differentiation, and induced to differentiate into monocytes and macrophages in various degree. The most effective inducer was dexamethasone and about 90% of the cultured cells were induced functionally and morphologically into mature macrophages by 10^-6 M dexamethasone.
The patient was treated with prednisolone (30 mg per day). Soon after the beginning of the treatment, a rapid disappearance of monoblasts, a gradual decrease of monocytes and an increase of hemoglobin were observed in the peripheral blood. Two months later, he achieved complete remission without passing through a severe cytopenic phase.
Not only the cytotoxic effect but the differentiation-inducing effect of prednisolone may lead to the successful induction of remission in this case.

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A 68-year-old male was admitted to the hospital because of facial edma, lumbago and back pain, and diagnosed as having multiple myeloma and azotemia. His general condition was improved by hemodialysis, transfusion and chemotherapy. However, the patient died of massive cerebral hemorrhage eighty-six days after admission. Immunoelectrophoresis of serum disclosed an M-bow in the β-globulin region. A molecular abnormality was suggested by the fusion of M-bow to the normal arc against anti-IgG and anti-λ serum in immunoelectrophoresis. Two spots were present in the thin-layer gel filtration; the major spot between the A and G fractions, and a minor one in the region posterior to the A fraction. The protein of the major spot reacted to anti-λ, anti-Fab and anti-Fc in immunogel filtration, and that of the minor spot was presumed to be Bence Jones protein. Thus the molecular weight of the M-protein was estimated to be about 80,000 with a partial structural deletion in the heavy chain, although it was IgG (λ) in dimer. In addition, the number of ribosomes composing polysomes in myeloma cells were counted in electron micrographs, and its distribution was analyzed. Polysomes increased at 7 and 9 in number of ribosomes composing polysomes. Multiple tumors were found in bone marrow at autopsy. Histologically, atypical plasma cells and plasmablasts diffusely proliferated in the tumors as well as the bone marrow, and infiltrated in the lymph nodes, liver, kidneys, and spleen.

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A 37-year-old woman was admitted to our hospital because of repeated eruptions in the lower legs, hepatosplenomegaly and monocytosis. Diagnosis of chronic myelomonocytic leukemia (CMML) was made by examinations of peripheral blood and the bone marrow. Repeated biopsies of the eruption showed panniculitis and severe infiltration of monocytic leukemia cells into the subcutaneous fat tissue. Combination of both panniculitis and skin infiltrations associated with CMML was rarely reported.

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A patient probably with acute megakaryoblastic leukemia associated with both hypodiploid and hypotetraploid clones is reported. A 59-year-old female was admitted to the hospital because of anemia. There were hepatosplenomegaly on physical examination and pancytopenia with the immature cells on the blood smear. These atypical cells were 25∼35 μm in diameter and negative for peroxidase, PAS, naphthol chroloacetate esterase, α-naphthyl butyrate esterase, but (+)-( ?? ) for acid phosphatase reaction. Aspirations of bone marrow were unsuccessful and a marrow biopsy disclosed diffuse myelofibrosis and loss of active hematopoiesis. Chromosomal analysis of blood without adding mitogenic agents showed 11 hypotetraploid cells of 31 metaphase cells. The diagnosis of acute leukemia was made and chemotherapy was done without success and died about 4.4 month later. Autopsy revealed diffuse bone marrow fibrosis, hepatosplenomegaly, enlarged kidneys and lymph nodes. Histologically showed the marked infiltration of atypical cells resembling to megakaryocytes and their immature forms. Although the origin of blast cells could not be proved clearly, this case is thought to be acute megakaryoblastic leukemia.

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A case of diffuse fasciitis with eosinophilia is described. The case was clinically characterized by malaise, slight fever and diffuse swelling, pain and stiffness of the forearms and legs. The skin was sclerotic and bound down to the underlying structure. There was no sigh of Raynaud's phenomenon, nor internal organ involvement as seen diffuse scleroderma. The laboratory study showed marked eosinophilia in both peripheral blood and bone marrow and hypergamma-globulinemia (IgG 1,990 mg/dl). Hemoglobin, hematocrit, platelet counts, ESR and urinalysis was normal. Skin tests for various parasites, antinuclear antibody, anti-DNA antibody, antimicrosome antibody and LE test were all negative. The en bock biopsy of the forearm showed marked fascial thickening together with mononuclear and eosinophile infiltrates, but there was no pathologic change in the epidermis, dermis and muscle tissue. The diagnosis was based on these histologic changes and above clinical features. The response to corticosteroid therapy was remarkable. Since Shulman reported the first two cases in 1974, about 100 cases have been documented in the world literature. Our case represent the sixth case in Japan. Although the cause and pathogenesis of eosinophilic fasciitis remain unclear, there have recently been several case reports which suggest an autoimmune mechanism, such as association with autoimmune thrombocytopenic purpura and aplastic anemia. The present case did not have such hematological complication, but should be followed carefully.

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A case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia characterized by cutaneous involvement was reported.
A 40-year-old woman was admitted because of skin rashes, generalized lymphadenopathy and fever. Since about 20 years of age the skin rashes which were brownish pigmentation and erythematous macules with slight purpura have always appeared over the trunk and the extrimities. In the bilateral axillary and inguinal nodes there were enlarged lymph nodes, 2×3 cm in maximum diameter. Hepatosplenomegaly was present.
Hypochromic microcytic anemia with polyclonal hyperimmunoglobulinemia was observed. Serum Fe, TIBC, transferrin were low and ferritin was elevated. Bone marrow aspiration revealed 4.2% plasma cells without atypsim. STS, PPD, DNCB and various autoantibodies were not disclosed. The right inguinal lymph node biopsy revealed follicular hyperplasia with germinal centers, prominent mature plasma cell proliferation between follicles and dilatation of the sinus. Histological examination of the skin rashes showed moderate infiltration of mature plasma cells and slight hemorrhage in perivascular area of the dermis.
Lymphadenopathy, skin rashes, fever and hypergammaglobulinemia were improved gradually by COP (cyclophosphamide, vincristine, prednisolone) therapy.

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The 79-year-old female patient with a huge spleen, pancytopenia and 10% abnormal cells in the peripheral blood was admitted to our hospital.
The abnormal cells showed hairy appearance under phase microscopy and were peroxidase (-), Naphthol AS-D chloroacetate esterase (-), α-naphthyl butyrate esterase (-), Acid phosphatase (+) and Tartrate-resistant acid phosphatase (-). Surface phenotype analysis of the abnormal cells by ABC immunoperoxidase method showed I2 (+), B1 (+), B4 (+) and MY4 (+). Cytoplasmic immunoglobulins (IgM, κ) were detected in these cells.
Cases of hairy cell leukemia with pancytopenia are rare in Japan. Clinical features of our case were compared with the cases in Japan and in western countries. The nature of hairy cells were also discussed.

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A 66 years old housewife was diagnosed as severe aplastic anemia because of pancytopenia and severe bone marrow aplasia. She was treated with bolus methylprednisolone (mPL) and antithymocyte globulin, but did not respond to them. After another course of mPL, she developed hepatitis. But her hematological condition was gradually improved. A third mPL therapy was then given and her response was good. Depletion of T-lymphocytes from bone marrow mononuclear cells by E-rosetting enhanced the colony formation of CFU-C. Analysis of T lymphocytes by using several monoclonal antibodies revealed that the normal ratio of OKT4/T8 before treatment converted to a reduced one after ATG administration, and suggested that activated suppressor T lymphocytes expressing HLA-DR⁺ were present in the blood after a good response to immunosuppression.
The results suggest that an immune mechanism suppressing hematopoiesis in our patient becane clear in the course of the disease and it continued after a good response to immunosuppressive therapy.

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A 49-year-old woman was admitted having dyspnea with eruptions on the precordium and extremities which lasted for a period of more than 6 months. Physical examinations disclosed hepatomegaly and left pleural effusion without any lymphadenopathies. Scaling eruptions with ulcer and bleeding rapidly extended over the entire body and the cutaneous biopsy revealed malignant lymphoma, of diffuse large cell type under the LSG classification. Surface markers on the tumor cells were positive for IgM, λ-chain, Ia, OKT10 and L-26, indicating a B cell origin and corresponding to centrocytes or centroblasts in the B cell lineage. In spite of the treatment with COPP, she gradually deteriorated and died of pulmonary insufficiency 107 days after administration. At the time of autopsy, as well as through out her clinical course, no lymphadenopathies were observed, though a moderate infiltration of tumor cells was found in the liver, spleen, both lungs and bone marrow.
This case with cutaneous lymphoma appears to be rare not only on account of its B cell origin but also the lack of any involvement of the lymph nodes, since most cutaneous lymphoma cases are of a T cell origin.

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A 53-year-old man referred to the Saiseikai Fukushima General Hospital on December 10, 1984, with chief complaints of meteorism, anorexia, general fatigue and fever.
On admission, the white blood cell counts were 60,300/cmm with 63% leukemic cells consisting of 14% myeloblasts, 2% promyelocytes and 47% immature monocytes. A bone marrow aspirate showed hypercellularity with 15.2% myeloblasts, 28.0% immature monocytes and 24.4% mature and immature eosinophils. The findings of peroxidase or esterase staining and of serum or urine muramidase activity supported the diagnosis of acute myelomocytic leukemia (M₄). Cytogenetic analyses revealed 46, XY, inv (16) (p13q22).
Complete remission was achieved after one course of chemotherapy consisting of aclarubicin, enocitabine, 6-mercaptopurine and prednisolone. In the beginning of January 1985, icterus, ascites and pleural effusion became remarkable probably due to liver cirrhosis and he died of acute respiratory failure on January 17, 1985.

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