[Mitoxantrone as combination chemotherapy in patients with acute leukemia. Tokai Blood Cancer Study Group].
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Acute Disease↗
Biomedical subjects
R Ohno
Publications and source records attributed to R Ohno.
Diversity of acute non-lymphocytic leukemia analyzed with monoclonal antibodies reactive with myeloid differentiation antigens.
The expression of myeloid differentiation antigens on acute nonlymphocytic leukemia cells (ANLL) was analyzed with four distinctive monoclonal antibodies (MoAbs); YM-1, HL-1, 20.2 and 20.3. These four MoAbs were shown to recognize different stages of differentiation of myeloid progenitor cells (CFU-GM) and/or mature myeloid cells. Consequently, leukemia cells of 68 adult patients with ANLL were able to be divided into four groups according to their expression of the antigens defined by these MoAbs: group 1 HL-1(-), YM-1(-), 20.2(-), 20.3(-) (13 cases); group 2 HL-1(+), YM-1(-), 20.2(-), 20.3(-) (16 cases); group 3 HL-1(+), YM-1(+), 20.2(-), 20.3(-) (13 cases) and group 4 HL-1(+), YM-1/20.2/20.3(+/(-)) (26 cases). This classification elucidated not only the maturation stages of ANLL but also the diversity of ANLL. When compared with the morphological classification, acute myeloblastic leukemia (AML) cases (M1 and M2 of the FAB classification) were evenly distributed among all four groups. These data suggest that the AML group was composed of heterogeneous leukemias which expressed surface phenotypes of different maturation stages ranging from the most immature stage to the mature stage. In contrast, the mature type (group 4) was composed of not only AML (M1 and M2), but also acute monocytic leukemia (M4) and acute myelomonocytic leukemia (M5). The clinical courses of these 68 patients revealed that the complete remission rate, remission duration and survival time were not significantly different among the four groups.
Adult↗
Phase I clinical and pharmacokinetic study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine.
A phase I study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 with hematological malignancies. The patients received either a 2-h single intravenous (i.v.) drip infusion (Schedule 1) or consecutive daily 2-h i.v. infusions (Schedule 2). In Schedule 1 the daily dose was initiated with 1.5 mg kg-1 which was escalated up to 7 mg kg-1. Side-effects were mild, and included nausea, vomiting, epilation, and hot flushes. Because of the presence of the solvent vehicle, HCO-60 and in consideration of the mechanism of action of BHAC, the dose escalation was stopped at 7 mg kg-1. In Schedule 2, the daily dose was started with 1.5 mg kg-1 which was escalated up to 8 mg kg-1 and given for 2-16 days. Myelosuppression was found to be dose-limiting toxicity. The maximum tolerated dose (MTD) in patients with non-hematological solid tumors was assumed to be 5 mg kg-1 daily X 5 days. The plasma disappearance curve of BHAC looked biphasic, and when 4 mg kg-1 of BHAC were administered the half-lives of the initial phase (t1/2 alpha) and the second phase (t1/2 beta) were calculated as 0.798 and 5.76 h respectively. In Schedule 2 complete remission was observed in 5 out of 21 patients with acute leukemia, one partial remission in Hodgkin's disease, and one 1-B response (Karnofsky) in thyroid papillary adenocarcinoma.
Adult↗
[Prognostic factors related to remission duration and the effects of maintenance therapy in BHAC-DMP therapy in adult acute non-lymphocytic leukemia patients].
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Acute Disease↗
Treatment of acute myelogenous leukemia in adults with N4-behenoyl-1-beta-D-arabinofuranosylcytosine.
Forty-five previously-untreated adult patients with acute myelogenous leukemia (AML) were treated with N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BHAC) in a multi-institutional cooperative study. Among 41 evaluable patients, 15 (36.6%) achieved complete remission (CR) and 10 (24.4%) achieved partial remission by daily administration of 3 to 8 mg/kg of BHAC. Higher daily doses (5 mg/kg or more) produced higher CR rates, and all of the CR were observed among the patients receiving a total BHAC dosage of 50 mg/kg or more in a period of 10 days or more. The side effects were mild and acceptable: nausea-anorexia was observed in 27% of the patients and vomiting in 17%. The results of this study thus indicate BHAC to be effective for remission induction of AML, and to deserve further clinical trials in combination with other anti-leukemic drugs.
Adolescent↗
Augmentation of generation of human allospecific cytotoxic T lymphocyte by PPD in in vitro sensitization culture.
PPD augmented human lymphocyte blastogeneic response to allogeneic lymphocytes in the mixed lymphocyte reaction (MLR) and generation of human cytotoxic lymphocytes against allogeneic human lymphocytes in in vitro sensitization (IVS) culture. The augmenting effect of PPD in the MLR was unequivocally synergistic at its lower concentrations (0.05 and 0.01 microgram/ml). The augmentation of MLR was observed following addition of a supernatant of culture medium of lymphocytes which had been precultured with PPD for 24 h then washed free of PPD and recultured without PPD for another 24 h. PHA and Con A, in contrast, suppressed both MLR and the generation of alloreactive cytotoxic cells. The alloreactive cytotoxic lymphocytes whose generation was augmented by PPD belonged to the SRBC-rosette forming fraction and passed through a nylon-wool column. The NK cell-like activities of the alloreactive cytotoxic lymphocytes were not augmented by PPD. Analysis of the alloreactive cytotoxic lymphocytes whose generation was augmented by PPD by competitive inhibition assay with unlabeled cells indicated that the same allogeneic lymphocytes used as sensitizing cells in IVS culture inhibited the cytotoxicity, while MOLT-4 cells, which are frequently used as target cells for the human NK-cell assay, did not. When lymphocytes with known HLA-A and HLA-B were used in the IVS culture and the cytotoxicity assay, PPD was found to augment the cytotoxicity only against the target lymphocytes that possessed the same HLA as the sensitizing lymphocytes in IVS.
Cells, Cultured↗
Treatment of plasma cell neoplasm with recombinant leukocyte A interferon and human lymphoblastoid interferon.
Thirty cases of plasma cell neoplasms (24 multiple myeloma, one plasma cell leukemia, and three primary macroglobulinemia) were treated with two kinds of highly purified alpha-interferons, recombinant human leukocyte interferon (rIFN-alpha A) (16 cases) and human lymphoblastoid interferon (HLBI) (14 cases). Partial remission (PR) was obtained in two of 16 evaluable cases treated with rIFN-alpha A and in two of 12 evaluable cases treated with HLBI. If minor response (MR) was included, responses were observed in seven (31.3%) and six (50%), respectively. Response (PR + MR) was noted in 38% of 21 previously treated patients and 71% of seven previously untreated patients. Side-effects were noted in more than two-thirds of the patients. They included fever, malaise, nausea/anorexia and myelosuppression. Thus, these two kinds of highly purified alpha-interferon were effective in plasma cell neoplasm, producing unequivocal response in 14.3% of the cases without unacceptable side-effects.
Aged↗
[Combination chemotherapy with cis-dichlorodiammineplatinum (11) (CDDP) and bleomycin BLM in advanced esophageal carcinoma].
Five patients with advanced carcinoma of the esophagus were treated with a combination chemotherapy employing CDDP and BLM. One cycle of chemotherapy consisted of CDDP, 50 mg/m2, on day 1 and BLM, 15 mg/patient on days, 1, 7 and 14. Two partial remission and 2 minor responses were obtained. Overall response rates, ths, were 80%. The most adverse effect was nausea. No significant elevation in the serum creatinine or BUN was recognized. Furthermore, the method of CDDP administration was studied on the serum level by 15 minutes' infusion and by 24 hours continuous infusion. The CDDP levels in the serum and tissue were determined by flameless atomic absorption spectrophotometry. The CDDP level in the serum by 15 minutes' infusion was higher than that by 24 hours continuous infusion. These results suggest that combination chemotherapy with CDDP and BLM may be a useful method for the treatment of advanced esophageal carcinoma.
Aged↗
[Sequential chemotherapy with low-dose methotrexate and 5-fluorouracil in advanced gastric cancer].
Sequential chemotherapy with low-dose methotrexate (30 mg/body) and 5-FU (750 mg/m2) was undertaken in 16 patients with advanced gastric cancer. Following the chemotherapy, leucovorin (30 mg/body) was injected intravenously. These treatment were repeated weekly for two to eight weeks. Out of 16 patients, two partial remissions and two minor responses were obtained. The overall response rate was 12.5%. There were no cases of renal or hematologic toxicity. The only adverse effect was nausea. We concluded therefore, that sequential chemotherapy with low-dose methotrexate and 5-FU is a useful method for advanced gastric cancer.
Adenocarcinoma↗
Establishment of a novel human megakaryoblastic leukemia cell line, MEG-01, with positive Philadelphia chromosome.
A megakaryoblastic cell line, designated MEG-01, was established from the bone marrow of a patient with blast crisis of Philadelphia (Ph1) chromosome-positive chronic myelogenous leukemia. MEG-01 cells grew in single-cell suspension with a doubling time of 36 to 48 hours. Under the usual culture conditions, approximately half of the cells adhered to the culture flask with extention of pseudopods. MEG-01 cells were positive for the periodic acid-Schiff reaction, alpha-naphthyl acetate esterase, and acid phosphatase, and negative for myeloperoxidase, alpha-naphthyl butyrate esterase, naphthol AS-D chloroacetate esterase, and alkaline phosphatase. Ultrastructural platelet peroxidase was positive in MEG-01 cells. Cytoplasmic factor VIII (FVIII)-related antigen was weakly positive in larger MEG-01 cells by both an indirect immunofluorescent technique with monoclonal antibodies and a direct immunoperoxidase technique using horseradish peroxidase-conjugated conventional rabbit anti-human FVIII antibody. Platelet glycoprotein (GP) IIb/IIIa antigen was uniformly demonstrated on the surface of MEG-01 cells by both indirect immunofluorescent and immunoperoxidase techniques using antiplatelet GP IIb/IIIa monoclonal antibodies; platelet GP lb antigen was demonstrated only in the cytoplasm of larger MEG-01 cells. MEG-01 cells possessed no markers for B or T lymphocytes or for myeloid cells. Chromosome analysis of this cell line revealed a human male hyperdiploid karyotype with a modal chromosome number of 56 to 58. The Ph1 chromosome was observed in all karyotypes analyzed. This novel human megakaryoblastic cell line may provide a useful model for the study of human megakaryopoiesis and of the biosynthetic mechanisms of proteins unique to megakaryocytic lineage.
Antibodies, Monoclonal↗
[Phase II study of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU)].
Sixty-seven patients with hematological malignancies and 4 with cancers were evaluated in this study. Standard administration of MCNU was instituted intravenously using 50-100 mg/m2 every 2 or 4 weeks, whereas some cases were treated with a higher dose therapy. Of 10 patients with chronic myelogenous leukemia, 7 achieved complete remission (CR), and 1 achieved partial remission (PR). A good response was also obtained in 9 of 10 patients with polycythemia vera and in all 4 patients with essential thrombocythemia. MCNU was less effective in malignant lymphoma (ML) and multiple myeloma (MM) than in myeloproliferative disorders. Two of 15 patients with ML and one of 21 patients with MM achieved CR, and two with ML and three MM achieved PR. Three patients with lung cancer and 1 with gastric cancer showed no response to MCNU. Delayed anemia, leukocytopenia and thrombocytopenia were observed in 38.7% of patients, and these were regarded as major side effects of MCNU. Nausea, vomiting, anorexia and elevated transaminase were also found in about 24% of patients, but only transiently. Our study indicates that MCNU is useful for chemotherapy of hematological malignancies, especially of myeloproliferative disorders. Therefore, further studies on combination chemotherapy with MCNU should be developed.
Adolescent↗
Immunological classification of adult lymphocytic leukemia based on the conventional cell markers and monoclonal antibody-defined cell surface antigens.
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Adolescent↗
[Bone marrow transplantation--problems and recent research trends].
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Adult↗
[Bone marrow transplantation from a phenotypically identical mother in a patient with acute lymphoblastic leukemia].
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Adolescent↗
[Treatment of severe infection in patients with hematological disorders by cefminox. Tokai Infection Study Group].
Sixty-three infectious episodes in 61 patients with hematological disorders were treated with cefminox (CMNX, MT-141), a new antibiotics in the cephamycin group. CMNX was given by 1 hour infusion every 8 to 12 hours in a dose of 4 to approximately 6 g per day for 3 to 12 days, not being combined with other antibiotics. CMNX was effective in 45% of total cases. In 24 cases, the number of granulocytes at the start of CMNX were less than 500/mm3, and 11 cases (46%) of them responded to CMNX. Thus, CMNX was found effective in severe infections in patients with hematological disorders. No serious side effects attributable to CMNX were noted.
Adolescent↗
Serological study for in vitro use of monoclonal antibody for autologous bone marrow transplantation in null cell-type acute lymphocytic leukemia.
In connection with autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) patients, the optimal conditions for in vitro elimination of leukemia cells from transplanted bone marrow cells with monoclonal antibodies (MoAb) plus rabbit complement (C) were investigated. Three monoclonal antibodies, NL-1, NL-22 and HL-47, which were produced in our laboratories and shown to react predominantly to Null-ALL cells, were used. In most cases, 10 micrograms/ml of MoAb and 50% of C were required for optimal killing of leukemia cells. Combined use of MoAbs and multiple treatments were studied, but generally no significant increase in the cytotoxicity to the target leukemia cells was observed as compared with a single treatment with the most effective single MoAb. Selection of C was very important, because some lots had lower C activity from the beginning or after incubation with normal bone marrow mononuclear cells. Nonspecific cytotoxicity to human hematopoietic cells was also observed in some lots of C. Under the optimal conditions thus defined, the three MoAbs did not inhibit the growth of granulocyte-macrophage colony-forming units (CFU-GM) or three other types of hematopoietic stem cells. Modulation of the antigens was also examined, and NL-1 antigen showed mild modulation, whereas NL-22 and HL-47 antigen did not. The results obtained indicated that these three MoAbs may be useful for eliminating Null-ALL cells in vitro from bone marrow in autologous BMT.
Antibodies, Monoclonal↗
Preliminary clinical trial of autologous bone marrow transplantation after in vitro monoclonal antibody and complement treatments in null cell-type acute lymphocytic leukemia.
Autologous bone marrow transplantation (BMT) in null cell-type acute lymphocytic leukemia (Null-ALL) was carried out after depletion of leukemia cells from transplanted bone marrow. Patients' autologous bone marrow cells were harvested during remission and treated in vitro with complement and three monoclonal antibodies (NL-1, NL-22 and HL-47) reactive to Null-ALL cells, and then cryopreserved. Three patients were transplanted with the antibody-treated bone marrow cells during the first remission period after preconditioning with intensive chemotherapy and total body irradiation, while transplantations in two other patients, who were in poor clinical condition, were done during the fourth remission period and the third relapse, respectively. Good preservation of hematopoietic stem cells after antibody treatment and cryopreservation of bone marrow cells was demonstrated in all five cases studied. Clinically, prompt recovery of white blood cells and platelets was observed in the three patients who received BMT during the first remission period; two of them have continued remission (2 and 15 months), while the other relapsed after 7 months of remission. these results suggested that autologous BMT with these three antibodies may be an effective mode of therapy for Null-ALL patients.
Antibodies, Monoclonal↗