[Clinical courses of 13 cases of long-term survivors after allogeneic bone marrow transplantation].
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Acute Disease↗
Biomedical subjects
R Ohno
Publications and source records attributed to R Ohno.
[Phase II study of a new nitrosourea derivative, MCNU, in tablet form. Takai Blood Cancer Study Group].
A phase II study of the oral agent methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU tablet) for myeloproliferative disorders was performed. Fifty-two patients were treated with MCNU tablets and 43 patients were evaluated for clinical effects and 45 for adverse effects. The standard regimen was as follows; oral administration of 50mg (one tablet)/body/day every 4-6 days was considered as one course, and this was repeated at 6-8-week intervals if possible, with certain modifications according to dosage, period of administration and dose interval wherever necessary. Of 16 patients with chronic myelogenous leukemia (CML) in the chronic phase, 13 achieved complete remission (CR), and 3 achieved partial remission (PR). The overall response ratio was 100%. Rapid reduction of leucocytes was detected within two weeks. One patient with CML in blast crisis achieved PR (100%). Of 15 patients with polycythemia vera, 13 showed an excellent effect (87%), and 1 a moderate effect (6.7%), the overall response ratio being 93%. In essential thrombocythemia, an excellent effect (70%) was obtained in 7 of 10 patients. One patient with myelofibrosis showed an excellent effect (100%). Nausea & vomiting (33%) and anorexia (13%) were major adverse effects, but these symptoms were observed only transiently. Liver dysfunction was also seen in 8.9% of patients, but no patient showed severe manifestations. Our study supports the contention that MCNU tablet is a useful agent against myeloproliferative disorders.
Administration, Oral↗
Phase I clinical and pharmacokinetic study of orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine.
A phase I study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg-1 which was escalated up to 24 mg kg-1 according to the modified Fibonacci's method. Side effects included nausea, vomiting and skin rashes, but myelosuppression was not seen within this dose range. In Schedule 2, the daily dose was started with 1 mg kg-1 which was escalated up to 24 mg kg-1. Major side effects were nausea, vomiting and anorexia, and mild myelosuppression was noted at 12 mg kg-1 or more. The dose-limiting toxicity was gastrointestinal toxicity, which appeared at 3.3 mg kg-1 or more and became frequent at 7 mg kg-1 or more. Pharmacokinetic study revealed that the plasma concentrations of PLAC and ara-C, obtained by the oral intake of 3.3 mg kg-1 or more of PLAC, were sufficient for these compounds to exert cytotoxic effects on various human leukemia cells in vitro. Based on these observations and plausible mechanism of action of PLAC, further clinical study should be carried out in a treatment schedule of considerably prolonged administration period with 3.3-6 mg kg-1 day-1 of PLAC.
Administration, Oral↗
Effect of recombinant human tumor necrosis factor on the colony growth of human leukemia progenitor cells and normal hematopoietic progenitor cells.
The effects of recombinant human tumor necrosis factor (rH-TNF) on the colony growth of human leukemia progenitor cells (L-CFU), granulocyte-macrophage progenitor cells (CFU-GM), and erythroid progenitor cells (BFU-E) were studied. L-CFU was assayed with leukemia cells obtained from patients with acute myelogenous leukemia. CFU-GM and BFU-E were assayed with bone marrow cells obtained from hematologically normal donors and patients with acute leukemia or non-Hodgkin's lymphoma in complete remission. A dose-dependent growth inhibition of L-CFU as well as CFU-GM and BFU-E was observed by rH-TNF at concentrations of 1 to 100 U/mL. The inhibitory effect on L-CFU was significantly greater than that on CFU-GM. No correlation was observed between the inhibitory effect on L-CFU and the number of colonies formed in the cultures without rH-TNF. Preincubation of the progenitor cells in culture medium containing 20% fetal calf serum with up to 1,000 U/mL of rH-TNF for 24 hours did not result in the inhibition of colony growth of L-CFU or CFU-GM. The inhibitory effect of rH-TNF was neutralized by an anti-rH-TNF murine monoclonal antibody.
Female↗
Treatment of multiple myeloma with recombinant interferon alfa-2a.
A Phase II study of interferon alfa-2a was conducted in 64 patients with multiple myeloma (42 IgG, 16 IgA, 5 Bence-Jones type, and 1 IgD) in a multi-institutional cooperative trial. Partial remission was obtained in 10 (21.3%) of 47 evaluable patients, and minor responses in 5 (10.6%) of 47. Remission was reached at 22 to 89 days (median, 29 days) after the initiation of interferon alfa-2a and lasted 4 to 55 weeks (median, 8 weeks). Side effects were noted in more than two-thirds of patients, and included fever (58%), malaise (20%), anorexia (52%), nausea-vomiting (26%), lethargy (2%), and myelosuppression (56%). They were all reversible on discontinuation of interferon alfa-2a. Antibody to interferon alfa-2a was detected in 1 of 20 patients tested during the course of treatment. Thus, interferon alfa-2a was effective in multiple myeloma, producing unequivocal response in 21.3% of patients without unacceptable side effects.
Antibodies↗
Randomized controlled study of chemoimmunotherapy of acute myelogenous leukemia (AML) in adults with Nocardia rubra cell-wall skeleton and irradiated allogeneic AML cells.
The effect of immunotherapy with Nocardia rubra cell-wall skeleton (N-CWS) on remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and having been consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N-CWS and irradiated allogeneic AML cells. Thirty-four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (P = 0.080) and on survival length (P = 0.098). When the data were analyzed at 30 months after the entry, there was a borderline significant difference in remission duration (P = 0.080) between the two groups, prolonging the 50% remission period by 110 days; but no significant difference in survival length (P = 0.314), although the 50% survival was 168 days longer in the chemoimmunotherapy group. However, there were 4 (18.2%) 5-year relapse-free survivors among 22 patients (11 in each group) who had been diagnosed more than 5 years before the time of the present analysis, and all of them belonged to the chemoimmunotherapy group (P = 0.090). Thus, immunotherapy with N-CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy.
Adolescent↗
Treatment of leukemia and myelodysplastic syndromes with orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine.
N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was administered PO to 76 patients with acute leukemia, myelodysplastic syndromes (MDSs), and myeloproliferative disorders (MPDs). Of 20 patients with acute myelogenous leukemia, 2 achieved complete remission, and the only patient with acute lymphoblastic leukemia achieved partial remission. Remission was reached with PLAC 100-300 mg/day 25-66 days after the start of therapy. Among 22 patients with MDS, 1 patient achieved a good response and 8 achieved partial response. Responses were reached with PLAC 50-200 mg/day 7-153 days (median, 33 days) after the start of therapy. Improvement of polycythemia was observed in all 5 patients with polycythemia vera, and reduction of thrombocytosis was observed in 5 out of 6 patients with essential thrombocythemia and myelofibrosis. An antileukemia effect was noted in 1 of 5 with chronic myelogenous leukemia. Major side effects were gastrointestinal toxicities and myelosuppression. In spite of the disadvantages, such as unpredictable absorption and a lower response rate to acute leukemia compared with its parent compound, this antileukemia Ara-C analogue that is administrable PO will be useful in the treatment of MDSs and MPDs, which do not necessarily require admission to hospital, and in the treatment of acute leukemia of the aged, a condition for which intensive chemotherapy is not appropriate.
Administration, Oral↗
Cellular hypersensitivity to nervous antigens in Guillain-Barré syndrome.
Cell-mediated immune responses to various nervous antigens were examined in 12 cases of Guillain-Barré syndrome (GBS), 24 cases of noninflammatory peripheral neuropathy (NIPN), and 18 cases of degenerative disorders of central nervous system (CNSDD), using the lymphocyte-transformation technique. Cellular hypersensitivity to bovine P2 protein (P2) and a synthetic peptide, SP66-78, corresponding to the residues 66-78 of P2, was detected in about two-thirds of GBS cases, especially in the active or improving stages, but not in NIPN and CNSDD. The lymphocytes sensitized to these nervous antigens might play an important role in the pathogenesis of GBS.
Antigens↗
Gamma-interferon production capacity and T lymphocyte subpopulation after allogeneic bone marrow transplantation.
T cell phenotypes after bone marrow transplantation (BMT) were investigated using monoclonal antibodies (moAbs) reactive to lymphocyte cell surface antigens. Patients' T cells showed decreased percentages of OKT4, 4A and 9.3-positive T cells, and increased percentages of OKT8, human Ia, and Leu-7-positive T cells. These changes in T cell phenotype persisted for a long period after BMT and had no correlation with the occurrence of graft-versus-host disease (GVHD). No lymphocyte activation antigens such as TIA (Tac) or transferrin receptor (5E9) were detected after BMT. The capacity of the patients' lymphocytes to produce gamma-interferon (IFN-gamma) was measured after incubation of lymphocytes with mitogen. Patients' lymphocytes produced significantly lower levels of IFN-gamma than the normal controls. This failure of IFN-gamma production showed no correlation with stimulation index of mitogen blastogenesis or changes of T cell population. Thus, not only T cell phenotype but also measurement of IFN-gamma production of lymphocyte may be useful in detecting immunological abnormalities in patients who receive BMT.
Adolescent↗
Biochemical characterization of human myeloperoxidase using three specific monoclonal antibodies.
We have developed three monoclonal antibodies (moAbs), MA1, MA3 and MB1, which react with different antigenic determinants of human myeloperoxidase (MPO). In MPO-positive culture cell lines, HL-60 and NKM1, analysis of MPO by pulse-chase experiments followed by immunoprecipitation with these moAbs revealed that MPO was composed of subunits of 59K, 18K and 14.8K dalton polypeptides which are plausibly derived from the 89 K precursor. MA1 and MB1 react with both the precursor and the mature forms of MPO. MA3 reacts with only the mature forms of MPO. Blocking experiments on MPO-related functions revealed that the three moAbs could be divided into two groups. MA1 and MA3 inhibit MPO activities such as tetraguaiacol formation, iodide oxidation and luminol-dependent chemiluminescence, while MB1 shows no such inhibition.
Adult↗
Behenoyl cytosine arabinoside, daunorubicin, 6-mercaptopurine, and prednisolone combination therapy for acute myelogenous leukemia in adults and prognostic factors related to remission duration and survival length.
Fifty-one consecutive previously untreated adult patients with acute myelogenous leukemia (AML) were treated with BHAC-DMP (N4-behenoyl-I-beta-D-arabinofuranosyl-cytosine, daunorubicin, 6-mercaptopurine, and prednisolone) therapy. Forty-two patients (82.4%) achieved complete remission (CR). The Kaplan-Meier analysis revealed a probability for remaining in remission of 14% and for survival of 23% at 6 years. Pretreatment factors related to the achievement of CR, such as age, French-American-British (FAB) classification and WBC at the start of treatment, were not identified. Factors related to the CR duration and survival time of the patients who had achieved CR were first analyzed by a univariate analysis with the generalized Wilcoxon test. WBC count at the start of treatment, percent of blasts in the marrow at 1 and 2 weeks after the initiation of therapy, days required until CR, number of courses of induction therapy required until CR, and days required for the disappearance of circulating blasts were identified as statistically significant prognostic factors. When these characteristics were further analyzed by the Cox multivariate regression model, the percent of blasts in the bone marrow at 2 weeks was the most important prognostic factor with a statistical significance, and WBC count at the start of treatment and days required until CR (or number of courses required to achieve CR) were also important factors, with borderline significance.
Acute Disease↗
[Clinical study of THP-adriamycin in patients with advanced gastric cancer].
To evaluate the therapeutic effects of THP-adriamycin (THP), single agent chemotherapy and combination chemotherapy with THP were undertaken in 16 patients with advanced gastric cancer. In the eight patients in the THP single agent group. Only three minor responses (MRs) were obtained. However, three partial remissions (PRs) and one MR were observed in the eight patients in the THP combination group. In which 5-FU was two patient FT-207 in another two and CDDP in one. No severe side effects were observed with the THP chemotherapy, while leukopenia of less than 3,000/mm was commonly seen (69%). Only three patients showed alopecia. Thrombocytopenia of less than 30,000/mm3 and transient arrhythmia were observed in one patient each. These side effects were apparently milder than those with adriamycin. From a pharmacokinetic study of THP and adriamycin. It was found that THP was superior to adriamycin in its transferability from the blood to cancer tissue. In conclusion, it is suggested that combination chemotherapy with THP is useful for advanced gastric cancer.
Adult↗
[Early phase II trial of bestrabucil in hematological malignancies].
Thirty-three patients with various hematological malignancies were treated with Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, at doses of 50-300 mg daily p.o., consecutively. Nineteen patients had previously received chemotherapy. Of 29 evaluable patients, there were one CR and three PRs among 6 patients with chronic lymphocytic leukemia, two CRs and one PR among 4 patients with malignant lymphoma, two PRs among 3 patients with adult T-cell leukemia, one PR among 4 patients with macroglobulinemia, one PR for one patient with essential thrombocythemia, and one PR for a patient with chronic myelocytic leukemia. Main side effects included G1 symptoms (14%), estradiol-related symptoms (24%) and myelosuppression (32%).
Adult↗
[Clinical evaluation of a combination therapy using cefmenoxime and cefsulodin on infections complicated by hematological disorders. Tohkai Research Group on Infections in Hematopoietic Disorders].
Infected patients with hematological disorders were treated with the combination of cefmenoxime (CMX) and cefsulodin (CFS). This therapy was done on 74 patients, of whom 38 (51%) had acute myelocytic leukemia, 14 (19%) malignant lymphoma, 7 (9%) acute lymphocytic leukemia, 5 aplastic anemia, 4 adult T cell leukemia, 4 chronic myelocytic leukemia, 1 multiple myeloma and 1 histiocytic medullary reticulosis. Complicated infections included 5 cases of septicemia, 41 cases of suspected septicemia, 19 cases of respiratory tract infection, 2 with anal abscess, 1 with urinary tract infection and others. The obtained results were as follows: Clinical effectiveness of the combination therapy was excellent in 17 cases (23.0%), good in 24 (32.4%) and poor in 33 (44.6%). Total clinical efficacy rate was 55.4%. Clinical efficacy rate was 40% against septicemias, 51.2% against suspected septicemias and 57.9% against respiratory tract infections. Causative pathogens were isolated in only 21 cases (28.4%): Gram-positive bacteria in 9 cases, Gram-negative bacteria in 11 and fungus in 1. About half of the Gram-negative bacteria belonged to Pseudomonas sp. The efficacy rate of this combination therapy against Gram-negative bacterial infections was 72.7% but the rate against Gram-positive bacterial infections were only 33.3%. Only in 1 case, this combination therapy was discontinued because of drug eruption. Abnormal laboratory findings were observed in 5 cases: Elevation of BUN in 3, GOT and GPT in 1 and prolongation of activated partial thromboplastin time in 1. In conclusion, this combination therapy of CMX and CFS is useful and safe against infections complicated by hematological disorders.
Adolescent↗
Adoptive immunotherapy against a local or widespread tumor of a highly malignant and poorly immunogenic mouse leukemia L1210.
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Animals↗
[Immunity in AIDS].
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Acquired Immunodeficiency Syndrome↗
Influence of pretransplant clinical conditions on the prognosis of patients treated with allogeneic bone marrow transplantation during leukemia relapse.
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Acute Disease↗
[Immunotherapy of acute myelogenous leukemia (AML) in adults with the Nocardia rubra cell wall skeleton].
The effect of immunotherapy with Nocardia rubra cell-wall skeleton (N-CWS) on the remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N-CWS and irradiated allogeneic AML cells. Thirty-four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (p = 0.080) and on survival length (p = 0.098). When the data were analyzed at 42 months after entry, there was a borderline significant difference in remission duration (p = 0.066) between the two groups, prolonging the 50% remission period by 120 days, but no significant differences in survival length (p = 0.306), although the 50% survival was 168 days longer in the chemoimmunotherapy group. Thus, immunotherapy with N-CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy.
Adult↗