Biomedical subjects
Publications and source records attributed to A Kanamaru.
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BHAC-MMP therapy, a combination of behenoyl-ara-C, mitoxantrone, 6-mercaptopurine and prednisolone, was applied to 49 patients with acute leukemia for remission induction. Complete remission was obtained in 6 out of 11 previously untreated patients (55%), and in 16 of 38 pretreated patients (42%). Median duration of complete remission was 41 weeks in previously treated patients, while 67% of untreated patients were still in complete remission. Most frequent side effects other than hematological toxicities were gastrointestinal disturbances, and GPT elevation etc., although most of these were not severe. In conclusion, BHAC-MMP therapy seems to be very promising for remission induction or for possible intensification treatment for acute leukemia.
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Micronomicin (MCR) at a daily dose of 120 to 360 mg was administered to patients with severe infections who had hematopoietic disorders as underlying diseases. Efficacy and safety of the drug were evaluated. The underlying diseases in the 56 patients included in the evaluation of efficacy were acute myelocytic leukemia (24 cases), acute lymphocytic leukemia (8), acute promyelocytic leukemia (6), acute monomyelocytic leukemia (4), acute monocytic leukemia (1), erythroleukemia (1), chronic myelocytic leukemia-blastic crisis (4), malignant lymphoma (3), aplastic anemia (2), and others (3). The infections were septicemia in 9 patients, suspected septicemia in 48, respiratory tract infection in 7, and perianal abscess in 2. The clinical efficacy of MCR was 'excellent' in 12 patients, 'good' in 17, 'fair' in 7, 'poor' in 30 for an efficacy rate of 43.9%. The efficacy rate classified according to infections was 22.2% in septicemia, 56.3% in suspected septicemia. The organisms isolated from the patients with septicemia were Escherichia coli in 2, Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 1, alpha-Streptococcus in 1, Serratia marcescens in 1, and Acinetobacter sp. in 1. The efficacy rate was 15.4% in the 13 patients whose causative organisms were identified. The efficacy rate for patients who had failed to respond to prior antibiotic therapy was 43.9%. The efficacy rate in patients (34 cases) with an initial neutrophil count less than 100/microliter was 44.1%. Side effect which might have been caused by MCR was skin eruption in only one episode among 83 episodes those were evaluated for safety.
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Twenty-five patients with malignant lymphomas were treated with etoposide oral capsule 200mg/day for 5 days, repeated 3-4-weekly. Twenty-one cases were evaluable. CR was achieved in four cases (19.0%) and PR in six cases (28.6%). The most serious adverse effect of the drug was leukopenia. In one patient (6.7%) the leukocyte count was lower than 1,000/mm3. Gastrointestinal toxicities such as anorexia, nausea, vomiting and diarrhea occurred in about 66.7% of patients but were not serious; alopecia was observed in 65.2%. In conclusion, etoposide is considered effective for malignant lymphomas.
One hundred patients with severe infections associated with hematologic disorders, including leukemia and lymphoma, were treated with ceftizoxime (CZX) in daily doses of 4 approximately 9 g for an average of 8.9 days. In the 84 patients who completed the trial, response was excellent in 27 (32.1%) and moderate in 25 (29.8%). The rate of effectiveness was 61.9%. The only side effect seen during the treatment was skin rash in 3 patients. Hepatic disorders were observed in 5 patients. The relation between CZX and these abnormal findings was not established. These results indicate that CZX is a therapeutically effective and safe antibiotic for the treatment of severe infections in patients with underlying hematologic disorders.
Serum obtained from (C3H X C57BL) F1 hybrid mice injected with parental (C57BL) lymph node cells after 600 rad irradiation contained a high level of an erythropoietic factor, which enhanced erythroid colony formation by fetal C57BL liver cells in methylcellulose cultures. The serum level of this erythroid colony-stimulating activity increased as the dose of lymph node cells injected increased and as suppression of endogenous spleen colonies (indicative of GVH severity) became more marked. Erythropoietin was also elevated in the sera of these mice. When these animals were transfused with washed packed red cells to induce plethora after sublethal irradiation and injection of lymph node cells, the erythropoietin level decreased, but erythroid colony-stimulating activity remained elevated. On the other hand, in anemic mice treated with phenylhydrazine, this erythropoietic factor was not detected, although the serum level of erythropoietin was elevated. These results suggest that a graft-versus-host (GVH) reaction may induce the production of an erythropoietic factor other than erythropoietin and that anemia itself may not be a stimulus for its in vivo production.
We surveyed cases of severe aplastic anemia treated by bone marrow transplantation from HLA-identical siblings according to information collected from 21 medical facilities throughout Japan. Twenty-nine patients have been given bone marrow transplants since 1977. Fifteen patients had survived for 20 to 2,485 days after bone marrow transplantation as of November 30, 1983. The one-year survival rate was 60% and the two-year survival rate was 44%. The incidence of rejection was 37% in patients with allogeneic bone marrow transplantation. Various regimens have been used for conditioning for bone marrow transplantation.
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The clinical effects of a new anti-viral 9-(2-hydroxymethoxymethyl) guanine (Aciclovir) against Herpes virus infections have been investigated. The patients had malignant tumours or auto-immune disease complicated by shingles and chicken pox due to Vaicella zoster virus (VZV) (43 cases), Herpes simplex virus (HSV) (10 cases) and 9 cases which were clinically diagnosed as Herpes, though the virus was not confirmed as the causative agent. As a general principle the dosage of Aciclovir was 5 mg/kg, t. i. d. for 5 days by slow intravenous infusion. The clinically effective rate against VZV was 93%, being excellent in 42% and against HSV it was 80%, being excellent in 40% and when the results of the cases of unknown origin were included it was excellent in 40% and the cumulative effective rate was 88%. Concerning the efficacy in reduction of pain, swelling, disappearance of vesicles and new scab formation, the effect was most noticeable after the third day of treatment. Treatment given early in the disease is likely to provide better results. Concerning side effects, one of 62 patients had proteinuria and the other had a drug rash and an abnormal liver function test. It is likely that the combination of treatment and the primary disease had some influence, but the cause/effect relationship to Aciclovir treatment is not clear.
Seventy-six patients with severe infection accompanying hematologic disorders including leukemia and lymphoma were treated with intravenous drip infusion of cefotetan (CTT). Of the 66 cases in whom the efficacy could be evaluated, 22 cases responded markedly and 16 cases moderately, the effective rate being 57.6%. It is impressed that more cases responded markedly to CTT than to any other antibiotics previously studied. None of the cases revealed serious side effects attributable to CTT. These results indicate that CTT is an effective and safe antibiotic for the treatment of severe infection accompanying hematologic disorders. As CTT was administered to special cases under marked decrease of neutrocyte, the importance of neutrocyte in the treatment of infection was also indicated.
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Fosfomycin (FOM) was administered intravenously to 65 cases of severe infections complicated with 62 cases of several haematological disorders. Out of 65 cases, 45 were treated with high doses FOM, i.e., 8 g per day or more. Another 20 cases were treated in usual doses of 4--6 g per day. Causative organisms were isolated from 52 cases of which 32 cases were Gram-negative bacilli and 19 cases were Gram-positive cocci. The effective rate of FOM was 57.8% in the high-dose treatment group (26/45) and 45.0% in the usual-dose treatment group (9/20), but the significant difference was not defined. Among 32 cases with Gram-negative bacilli infections, including Pseudomonas aeruginosa or Serratia marcescens, 15 cases were effective (47%). On the contrary, 14 out of 19 cases with Gram-positive cocci infections were effective (74%). Thirteen cases (50.0%) were effective even in which neutrophils were less than 500/cmm before FOM administration. Severe side effects were not observed, without 2 cases. One was skin eruption due to drug allergy and the other was suspected to be interstitial pneumonitis, but not confirmed pathologically. These data suggest that high dose treatment of FOM were useful for the severe infections even in neutropenic state in haematological disorders.
A total of 48 patients with various malignant disorders, mostly from hemopoietic organs, entered to phase I study of MCNU given orally. Fifty-six percent of the patients given MCNU at the doses of 50-125 mg/m2 complained of gastrointestinal symptoms including nausea and vomiting, which were however mild and well tolerated. In the following study employing administration of 50 mg/day of MCNU for consecutive 2-6 days, the gastrointestinal toxicities were reduced to 26.1%, and hematological toxicities of delayed leukopenia and thrombocytopenia were derived 4-6 weeks after oral intake of the drug. The hematological recovery required 1-2 weeks after the nadir of leukocyte and thrombocyte count. A recommended dose for phase II study of MCNU by the route of oral administration was 50 mg/body/day for consecutive 4-6 days in every 8 weeks interval. The peak value of blood concentration of MCNU was obtained 60-120 minutes after p.o. administration at the doses of 50-100 mg. Elimination half-life was estimated to be 40-45 minutes. No concentration of the drug was detected in blood 24 hours after the administration.