The relationship between the degree of the initial hematological impairment and the survival terms was analysed in 190 cases of aplastic anemia registered by the Ministry of Health and Welfare Specific Disease (aplastic anemia, idiopathic hematological disorders) Research Committee using the criteria for grading the severity of this disorder which had been reported by us.
In terms of the degree of the initial hematological impairment, 190 cases were divided into 3 groups: 76 cases (40.0%) were severe, 79 cases (41.6%) were moderate, and 35 cases (18.4%) were mild. Survival rates for these 3 groups were clearly different at any time throughout the follow-up period. The mortality rates evaluated at the 6th month after the onset of symptoms were 55.3% in severe, 17.7% in moderate, and 0% in mild cases. On the contrary, survivors for more than 5 years after the onset of symptoms were 15.8% in severe, 55.7% in moderate, and 80.0% in mild cases respectively.
The results of the present study clearly show the closed correlation between the degree of the initial hematological impairment and the survival periods of the patients with aplastic anemia. Thus, grading of the severity using the criteria reported by us would help us to estimate the prognosis of the patients with aplastic anemia.

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Eight (9.4%) of 85 patients with non-Hodgkin's lymphoma admitted in our hospital during the past ten years developed the meningeal involvement. These 8 patients had a diffuse histologic subtype. At the time of diagnosis of the meningeal involvement, other extranodal sites were already involved in five patients, and the most commonly involved extranodal site was bone marrow.
Local treatment with intrathecal chemotherapy and/or whole brain irradiation was effective, but systemic treatment with intensive combination chemotherapy was not effective. So the survival range after the developement of the meningeal involvement was very short, and six patients died within three months.

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N⁴-behenoyl-1-β-D arabinofuranosylcytosine (BH-AC) is a newly synthesized derivative of cytosine arabinoside which is resistant to cytidine deaminase and is remarkably dose-independent in its antileukemia L 1210 effect. Aclacinomycin A is a new anthracycline antibiotic which is as effective as daunomycin against leukemia L 1210. It is reported to be less cardiotoxic and induce no alopecia. Phase I and II clinical studies revealed their effectiveness against human acute leukemia. We combined, therefore, the two new agents with 6-MP and prednisolone as a pilot study for remission induction in acute non-lymphocytic leukemia (ANLL). The treatment schedule consisted of daily administration of BH-AC 116 to 234 mg/sq. m as an iv infusion for 2 hours, aclacinomycin A 12 to 16 mg/sq. m as an iv infusion for 30 minutes, and oral administration of 6-MP 100 mg/sq. m and prednisolone 40 mg/sq. m. The treatment was continued until bone marrow became severely hypoplastic.
Eight adult patients with ANLL were entered for study. One patient was excluded because of an early death due to acute renal failure. Among seven evaluable patients, six obtained a complete and another a good partial remission. Only one course of treatment was administered in five of six patients before a complete remission occurred. It is to note that a complete remission was attained in two of three patients who had been resistant to DCMP therapy. The treatment was continued for 6 to 14 days, a median 10 days. Currently, the duration of complete remissions is from 4+ to 6 2/3 months and that of survival is from 6+ to 27+ months with a median 10 1/3+ months. Most frequent side effects included general malaise and gastrointestinal symptoms, such as nausea, vomiting and anorexia. These were observed in a half of the patients. Melena was noted in three. Flat T waves were noted in ECG of two elderly patients; the change, however, was not clearly attributed to drugs employed. Two patients suffered from moderate epilation. All of the side effects were tolerated by the patients and the treatment was not interrupted due to any of them.
This regimen is quite effective as a remission inducer in human ANLL and its toxicity is moderate. It deserves further studies.

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Thirteen cases of hereditary deficiency of erythrocyte pyruvate kinase (PK) associated with hemolytic anemia, who were considered to be heterozygous for two different alleles, were studied clinically and biochemically. Characterizations of these abnormal PKs were performed according to the methods recommended by the International Committee for Standardization in Haematology (ICSH). Following ICSH recommendation, each patient was named PK “Kagoshima”, PK “Kyoto”, PK “Takamatsu”, PK “Abeno”, PK “Kobe”, PK “Marugame”, PK “Hoenzaka”, PK “Osaka”, PK “Motomachi”, PK “Gifu”, PK “Hiroshima, PK “Matsumoto”, and PK “Tama”.
The characteristics of mutant PK enzymes suggest that the causes of chronic hemolysis depend mainly on decreased affinity for phosphoenolpyruvate, thermolability, increased inhibition by adenosine triphosphate and low activation by fructose-1, 6-diphosphate.

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We have investigated the in vitro effect of Lithium on mononuclear cells (MNL) and on bone marrow cells from two patients with congenital neutropenia. Both patients (13 month old girl and 11 month old girl) had severe recurrent skin and respiratory infections. The bone marrow had 20∼30% neutrophil precursors with an arrest at the stab stage. Colony stimulating activity (CSA) of patient 1's MNL was hyperactive and did not increase by adding 1 mEq/L of Lithium. On the other hand, CSA of patient 2' MNL was increased by Lithium. Both patients were given oral Lithium carbonate and serum Lithium was maintained around 1 mEq/L over 16 weeks. They showed beneficial response in peripheral granulocyte counts and in serum unsaturated vitamin B₁₂ binding capacity. Thus there could be another mechanisms of Lithium on granulopoiesis (Patient 1) than the enhancement of production of colony-stimulating factor by MNL (Patient 2). Incidence of fever and infection of both patients appeared to be lower during Lithium therapy. Neither patient experienced any severe side-effects from Lithium except transient vomiting and diarrhea. These preliminary results suggest that Lithium therapy could be useful in some patients with congenital neutropenia.

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Fifty two children with acute leukemia and solid tumor were immunized with various vaccines during remission. A varicella vaccine was given to twenty two subjects with acute leukemia and twenty three subjects with solid tumor. Skin tests with varicella antigen were positive in more than 90% of these patients after vaccination. Adverse reactions, such as fever and rash, were found frequently in patients on cancer chemotherapy but symptoms were transitory and mild. Measles, rubella and mumps vaccines, alone or mixed, were performed in seventeen patients who had been off chemotherapy. Majority of vaccinated children developed significantly high antibody responses. Vaccines of influenza, Japanese encephalitis, DPT and BCG were given to a few patients with minimal adverse reactions. Natural viral infection after vaccination was found only one patient with neuroblastoma who had received varicella vaccine.
These results suggest various vaccination would be recommended even in children with malignancy whose immunological function might be disturbed by chemotherapy or irradiation.

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We report of a 13-7/12 year old boy with congenital pernicious anemia. His first anemic episode was seen at 1-8/12 year old. His anemia responded well to the therapy of vitamin B₁₂ and folic acid, and improved dramatically. Thereafter, he had been symptomless for about 12 years untill a month prior to this visit and admission to our clinic.
He had atrophic gastric mucosa with normal gastric acid secretion and transitory selective malabsorption of vitamin B₁₂. Both of these findings are different from those of typical case with congenital pernicious anemia, and possibly derived from the prolonged vitamin B₁₂ deficiency.
We would like to follow carefully whether he will develop to other types of pernicious anemia associated with achlorhydria, and/or with antibodies to the intrinsic factor or to the parietal cells.

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A 32 year old male patient was admitted to our hospital because of general malaise, generalized skin eruption and bilateral cervical tumors. On his admission, physical examinations revealed bilateral cervical lymph node enlargement and generalized papuls with petechiae. Peripheral blood examinations showed the hemoglobin 13.7 g/dl, the platlet count 8,000/mm³ and the white blood cell count 12,200/mm³ with 70% myeloblasts. The bone marrow aspiration revealed hypercellular marrow with 60% myeloblasts. From the finding of peripheral blood and bone marrow, he was diagnosed as acute myelogenous leukemia. The histology of cervical lymph nodes and skin eruption, however, showed epitheloid granulomas of sarcoidosis. Since sarcoid granulomatous lesions were found in two different organs, it was considered that these lesions were not sarcoid tissue reactions in AML but the lesions caused by sarcoidosis itself. Occurrence of AML in this patient could be related to sarcoidosis since it is well known that patient with sarcoidosis have some abnormalities in cellular immunity and surveillance system against malignansy. This is the first case of AML associated with sarcoidosis.

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With increasing frequency of case reports of patients with malignant lymphomas occurred subsequent to autoimmune diseases, relationship between autoimmune diseases and the development of malignant lymphomas has been noticed immunologically. However, in Japan, reports of such cases are few.
We reported a case of malignant lymphoma with monoclonal gammopathy via hypogammaglobulinemia occurred subsequent to idiopathic thrombocytopenic purpura after treatment of corticosteroid for 3 years and 6 months.
Cases of malignant lymphomas occurred subsequent to autoimmune diseases from the literature were reviewed and discussed.

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A 29-year-old man was admitted to our hospital because of dyspnea and fever. Physical examination showed pyoderma in face. Lymph nodes were not palpable and hepatosplenomegaly was not noticed.
Laboratory findings revealed pancytopenia and hypofunction of celluar immunity in immunological studies. Bone marrow study observed hypocellular that 22 percent consisted of reticulum cells which had characteristics of PAS (±) peroxidase (-), acid phosphatase (+) and tartrate resistant (+).
He was treated a number of antibiotics and blood transfusions but vigorous treatments failure to save his life and he died due to respiratory infection about eleven months after onset. The autopsy was performed, it showed hemosiderosis due to frequent blood transfution and reticulum cell proliferation with erythrophagia in the spleen, bone marrow and liver. Histological diagnosis was reactive reticulosis.
The systematic classification of reticulosis was formulated by Kojima and Rappaport, but there are still controversial problems. In this paper we reported that our case followed on fatal course despite reactive reticulosis histologically, and reticulosis was discussed.

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An autopsy case of acute myelocytic leukemia preceded by hemopoietic dysplasia, presumably on a sequela to the atomic bomb in Hiroshima is reported.
On admission, severe anemia and thrombocytosis were found and the bone marrow aspiration showed myeloid hyperplasia without definite maturation arrest. Mild to moderate eosinophilia and basophilia continued during the course of the disease, accompaning mild monocytosis 2 years later. Furthermore, he had the radical operation for the early gastric cancer in this preleukemic stage. After the administration of methenolone acetate (25 mg/day), severe anemia has dramatically improved, but leukocytosis with profound monocytosis persisted, and subsequently acute myelocytic leukemia developed. He died from an intracerebral bleeding due to an accidental trauma on the head. Autopsy findings disclosed the systemic leukemic infiltration.
Repeated chromosome analyses revealed the mosaic karyotype of 46, XY/45, XY, -16 on admission, but it was 46, XY/46, XY, del (8) (p 12) in the overt leukemic phase. The granulopoietic colony forming capacity of bone marrow cells was already low one year before the oncet of overt leukemia. This finding suggested that the existence of an abnormal clone could be predictable. In addition, the possible causative effect of the exposure to the atomic bomb in leukemogenesis in this case is discussed.

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A case of acute myeloblastic leukemia associated with central diabetes insipidus was reported. The 54-year-old male was admitted to the hospital with the chief complaints of fever, thirst and polyuria. Physical examination showed the generalized lymph node enlargement, anemia and hepatomegaly without splenomegaly. Laboratory examination on admission disclosed macrocytic anemia, leucocytosis with 86 per cent of myeloblasts and the elevated lactic dehydrogenase.
Bone marrow revealed markedly increased myeloblasts. Urine volume daily was over 5 liter and specific gravity of urine was 1.006. The level of antidiuretic hormone was low. Vasopressin test was positive. Diabetes insipidus was treated by 1-deamino-8-D-arginine vasopressin and the therapy was effective. After 2 months from the onset, the patient died of DIC. Autopsy was not done. The association of acute myeloblastic leukemia with diabetes insipidus seems to be rare. The pathogenesis of this disease was discussed.

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A 61 year-old female case of pernicious anemia complicated with Hashimoto's thyroiditis was reported. In 1970 she noticed swelling of her front neck and was diagnosed to have Hashimoto's thyroiditis with strongly positive thyroid antibody. After treated adequately for nine years, she felt burning of her tongue and headache, and was revealed that she suffered from pernicious anemia complicated with Hashimoto's thyroiditis. The anemia got better by parenteral treatment of hydroxocobalamine.
Recently the relationship between pernicious anemia and Hashimoto's thyroiditis has drawn attention and their causal development was discussed in this paper.

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A case of “microgranular” acute promyelocytic leukemia (APL) is reported.
The patient, a 19-yr-old female was admitted to our hospital because of epigastralgia and hemorrhagic tendency. On physical examination on 1/2/80, she was found to be not so pale but suffered from genital bleeding. There were some ecchymoses and petechiae on extremities. Her temperature was 38.8°C. The hemoglobin was 13.1g/dl, the WBC counts 93,500/μl, the platelet counts 22,000/μl, the prothrombin time 18.2 sec (control: 12.0 sec), the plasma fibrinogen 41.5mg/dl, and the fibrin degeradation products 40μg/dl (normal: <20μg/dl). The atypical cells were found 93% in the peripheral blood as well as 94.4% in the bone marrow. This atypical cell had only a few fine, dustlike azurophilic granules, but neither Auer rods nor progranules. The chracteristic distribution of granules seen in APL was observed only by transmission electron microscopy.
BHAC-DMP therapy was begun for initial remission induction chemotherapy with combined use of heparin. Twelve days after the start of the chemotherapy, the atypical cells of BM showed the presence of numerous coarse, azurophilic granules seen in APL and multiple Auer rods in Wright-Giemsa stain. A complete remission was achieved by BHAC-DMP regimen, which was maintained for 17 days. During relapse of APL, cytogenetic analysis with banding techniques, of cells from BM and unstimulated PB revealed no abnormalities such as the 15; 17 translocation. The patient died on 10/9/80.
This paper should be the first case report of “microgranular” APL in Japan on literatures.

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Thia is to report a case of severe aplastic anemia having T lymphocytes in peripheral blood which suppressed both CFU-E colony formation and immunoglobulin production in vitro. A 15 year-old male was referred to our hospital because of progressive pancytopenia which had been noticed for one month. On physical examination severe anemia in conjunctiva was noted. Hematological examination revealed hemoglobin of 5.0g/dl, reticulocyte of 0.7%, platelet count of 1.3 x 10⁴/μl and neutrophils of 476/μl. Bone marrow was hypocellular and 87.2% of nucleated cells were lymphocyte. Ferrokinetic study revealed PID T 1/2 of 320 min. and RIU of 10%. Immunologically, 89.3% of peripheral blood lymphocyte had T cell markers, of which 45.6% were Tγ cells. T cell had a suppressor activity for immunoglobulin producing cells. Bone marrow co-culture studies prior to transfusion revealed that peripheral T cells had a suppressor activity for CFU-E but not CFU-C. He did not respond to treatment and expired 87 days after first visit. In this case, pathogenetic significance of T lymphocytes was uncertain, but it played some role for the clinical course. Furthermore, progressive lymphocytopenia in this patient suggested a derangement in lymphoid stem cell or pluripotent stem cell.

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A 42-year-old male patient with acute promyelocytic leukemia complicated with DIC and in incomplete remission, underwent a bone marrow transplantation from his HLA-matched and MLC-nonreactive brother, with an uneventful effect, achieving complete remission. Successful engraftment has been confirmed indirectly by the hematological improvement by day 30 in spite of lethal pretreatments such as high doses of cyclophosphamide and 1,000 rad total body irradiation.
No obvious graft-versus-host disease (GVHD) occurred.
Interstitial pneumonitis developed at day 70 and seemed to be controlled in a short time with a high dose of prednisolone.
But severe interstitial pneumonitis complicated with Herpes zoster at the right leg reappeared on day 109 and was treated with prednisolone, azathioprine, and interferone with no effect. He died on day 121.
An autopsy revealed epidermal Herpes zoster virus infection and Pneumocystis carinii and Cytomegalovirus infection in the lung and liver. No evidence of leukemic cell infiltration was seen.

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A 33 year old chinese man was admitted to our hospital on January 8, 1979, with posttransfusional hepatitis after partial nephrectomy with nephrolithiasis. Hypochromic microcytic anemia was noted (Hb 10g/dl, RBC 461×10⁴/mm³, Ht 30.0%). Leukocyte and platelet counts were normal. Anisocytosis, poikilocytosis, basophilic stippling and target cells were seen in the peripheral blood. Serum iron was 255μg/dl and total iron binding capacity was 302μg/dl. Serum folic acid and Vitamin B₁₂ were normal levels. Hemoglobin F was significantly elevated, and A₂ was normal. Red cell fragility with coil planet centrifuge was markedly decreased (hemolytic pattern was R type). The bone marrow aspirate revealed erythroid hyperplasia and increased sideroblast. Ringed sideroblast was not observed.
His father, elder sister and younger sister's blood data were similar to propositus. The diagnosis of β-thalassemia (δβ-thalassemia) minor transmitted from the father's side was established when propositus admitted with posttransfusional hepatitis.
Coil planet centrifuge is seemed to be useful to find out latent thalassemia.

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