Eight adult patients with acute leukemia were treated with quadruple combination therapy of cyclocytidine, adriamycin, 6 MP and prednisolone. Cyclocytidine (10 mg per kg of body weight per day) and adriamycin (0.6∼0.3 mg per kg of b.w. per day) were administered intravenously by drip-infusion, and 6 MP (2.0∼1.6 mg per kg of b.w. per day) and prednisolone (0.8∼0.6 mg per kg b.w. per day) orally, each for four days. Thereafter no anti-leukemic drug was administered, except for a lower dose of prednisolone. It was thought to be appropriate to institute the next course of therapy from thirty to sixty days after the previous one, until the recovery of the normal hematopoiesis. After two or three courses of therapy, seven patients (four with acute myeloblastic leukemia, two with acute lymphoblastic leukemia and one with acute promyelocytic leukemia) gained a complete remission. Five of them showed almost normal bone marrow morphology. One patient with acute basophilic leukemia gained a partial remission. The complete remission was obtained between 23 and 110 days after the start of the first therapy. So far the duration of remission was two to six months in cases of AML and over ten months in a case of APL.

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The in vivo cell cycle effects of cytosine arabinoside (Ara-C), Vincristine (VCR), and massive leukapheresis on human leukemic blast cells in bone-marrow have been studied in 15 patients with acute leukemia.
Mitotic index (MI) and ³H-thymidine labeling index (LI) were determined in the repeated marrow samples before the study and at intervals thereafter for the duration of study. Eight patients were given intravenous injection of Ara-C over 19 courses in a dose of 70 mg/m² for 2 consecutive days. Computor analysis indicated that statistically significant increase in LI was seen 48 hours after the injection, implying partial S-phase synchronization of leukemic cells. Five patients were given intravenous injection of VCR in a dose of 0.6 mg/m² and no significant change in LI was seen until 48 hours after the injection. No significant change in MI was observed either by Ara-C or VCR.
Massive leukapheresis by means of Celltrifuge was done in three patients with acute leukemia and two patients with chronic myelogenous leukemia. In one patient with acute myelogenous leukemia, peripheral leukocyte counts were reduced from the level of 10.2×10⁴/cmm down to 6.9×10⁴/cmm., and the nucleated marrow cell counts were reduced from 112.2×10⁴/cmm. to 18.6×10⁴/cmm., through the extraction of 26.6×10¹⁰ leukocytes. LI was significantly increased after leukapheresis, whereas MI was significantly reduced inversely. The result was reproduced by the second leukapheresis in the same patient.
A new quadruple combination chemotherapy (Neo-DCMP) was designed, applying the said results of partial synchronization with Ara-C, and 9 patients with acute leukemia were treated, of whom 6 developed complete remission.
Sequential changes in LI of both leukemic blast cells and normal myeloid precursors were determined during the course of therapy and the results were discussed in view of cell cycle effects of chemotherpy.

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130 cases of leukemia with tumor formation including our own 5, except chloroma, which were reported in Japan from 1953 to 1973, were summerized to discuss their clinical manifestation, treatment and prognosis.
The results were as follows.
1) The incidence of tumor formation was frequent in bone including bone marrow, mediastinum, skin and kidney.
2) In acute leukemia tumor appeared most frequently in its initial stage but recently the incidence increased in the remission stage according to the progress of chemotherapy.
3) In chronic myelogenous leukemia tumor formation suggests acute exacervation.
4) On the treatment to tumor better results were obtained in acute lymphatic leukemia, but poor results in chronic myelogenous leukemia.
5) In our 5 cases combination chemotherapy with Neocarzinostatin was proved to be excellent for tumors.
6) In the treatment to tumor extirpation should be performed for localized tumor. Irradiation is considered to be one of the effective method. Chemotherapy is less effective, but combination chemotherapy including Neocarzinostatin is more effective therapy.

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The mechanism of the intravascular hemolysis of erythrocytes of the patients with paroxysmal nocturnal hemoglobinuria (PNH) has not been defined yet. The protective effect of vitamin E on the erythrocyte membrane in a case of PNH was examined in vitro and in vivo.
The sugar water test was performed as a diagnostic aid of PNH. The hemoglobin concentration of the supernatant in the suger water test reduced to 70 to 80 per cent of the control when vitamin E was added in vitro.
After the administration of vitamin E (100 mg/day, parenterally) for about 4 weeks, the attacks of the hemolysis subsided and the anemia of the patient improved.
These facts mean vitamin E could inhibit the hemolysis of PNH erythrocytes stabilizing the erythrocyte membrane in vitro and in vivo.

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A 23-year-old woman with acute myelocytic leukemia had passed a normal delivery. On a regular check-up at the ninth month of her pregnancy, she was found to be anemic and diagnosed as acute myelocytic leukemia on a blood smear. At that time, white blood cell count was only 900/mm³.
After the delivery, she was treated with daunomycin, cytosine arabinoside, 6 MP, and prednisolone. Although her general condition was once markedly improved, the complete remission was not obtained. Seven months later, she died from severe esophageal bleeding.
Her seven-month-old baby revealed no leukemia.

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A case of hereditary spherocytosis with nephrotic syndrome in a 10-year-old boy was described. In this patient, when serum cholesterol levels was elevated, the red blood cell counts, mean red blood cell diameter, reticulocytes counts and serum bilirubin levels turned to be normal.
A possible mechanism of serum cholesterol to increase the red blood cell stability was discussed.

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8 cases of chronic myelogenous leukemia and 3 cases of polycythemia vera were treated with new alkylating agent: No. 864-T (bis (3-mesyloxypropyl) amine p-toluensulfonate) that had been administrated orally 30-90 mg daily dosis, and their clinical and hematological states were discussed.
In chronic myelogenous leukemias, the effects of No. 864-T were very excellent.
Peripheral leukocyte count reduced about 1×10⁴/cmm within 1-3 months, and spleen size reduced completely.
In polycythemia vera peripheral erythrocyte count reduced about 450×10⁴/cm within 1-3 months, and complete remission were induced.
But our cases, other blood components was also affected slightly.
Therefore, it was suggested that the effects of No. 864-T were specific to leukocytes in chronic myelogenous leukemia, erythrocytes in polycythemia vera.
In our studies, No. 864-T will be useful for treatment of chronic myelogenous leukemia and polycythemia vera.

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A 47 years old female, who had received oophoro-hysterectomy because of uterine carcinoma and postoperative irradiation therapy of excessive dose to the pelvic and lower abdominal regions in 1959 and consequently suffered from normochromic anemia which was said to be due to the irradiation and treated with transfusions, visited our hospital because of anemia in April, 1970.
At that time she was diagnosed as atypical hypoplastic anemia because of pancytopenia in the peripheral blood and relatively hypererythroid marrow.
Two years later, in March, 1973, she suddenly developed high fever, general fatigue, severe anemia. Hematological study revealed acute myeloblastic leukemia. Combination therapy of DM, 6 MP and prednisolon together with blood transfusions were given with no effect and about 3 months after onset of leukemic manifestations, she suddenly died of asphyxia due to a large amount of hemoptisis. Autopsy revealed lung bleeding in the background of leukemia.
Irradiation-induced leukemia and early diagnosis of leukemia and/or preleukemia have been discussed in some detail reviewing the related literature.

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A 10-year-old (at the time of demise) boy received radiotherapy for swelling of the back of the right foot when he was one year and 4 month old. Around the age of 5 years he began to have frequent nose bleedings. He was examined periodically, but no definite diagnosis was made, At the age of 9 years he became anemic necessitating frequent blood transfusions. Toward the end of 9 years immature monocytes began to increase both in the peripheral blood and bone marrow. He died of cerebral hemorrhage. His illness during the period of about 4 years after he began to have nose bleedings was considered not to be aplastic anemia or other types of anemia but preleukemia in view of the following findings: 1) increase of atypical lymphocytes and monocytes early in his illness 2) presence of giant platelets early in his illness 3) atypical bone marrow histology and 4) abnormal bone marrow scintigram pattern.

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Excessive plasma protein loss into gastrointestinal tract is a major cause of hypoproteinemia, and has been characterized as protein-losing gastroenteropathy. But, neither the mechanism of increased leakage of plasma protein to gastric or intestinal mucosa, nor the specific treatment for the disease has yet been clearly established. This is a first report of protein-losing gastroenteropathy, in which the tissue activator of plasminogen was introduced as a causative factor of increasing permeability of plasma protein to mucous membrane of digestive tract.
In two cases of protein-losing gastroenteropathy, one with erosive gastritis and the other with Menetrie's disease, biopsied gastric mucosa was found to contain markedly increased tissue activator of plasminogen, suggesting the fibrinolysis might participate in the enteric loss of plasma protein. The former case, as well as a case of Crohn's disease, were treated with antiplasminic compound trans-4-aminomethyl cyclohexane carboxylic acid (t-AMCHA), and dramatic effect to prevent the loss of protein was observed. Especially in the former case, underlying disorder could be reduced by the therapy, probably be explained by the effect of t-AMCHA which blocked the vicious circle of “membrane damage”—“increased tissue activator”— and “hypoproteinemia”. Further, abnormal loss of protein in Menetrier's disease was found to parallel to the increase of tissue activator.
These evidences strongly support the new concept that the tissue activator of plasminogen plays an important role in the pathogenesis of protein-losing gastroenteropathy.

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