Search PubMed⌕ Search

Biomedical subjects

R Ohno

Publications and source records attributed to R Ohno.

At least 217 records · Page 12Linked to original sources
PubMed1994

All-trans retinoic acid therapy in relapsed/refractory or newly diagnosed acute promyelocytic leukemia (APL) in Japan.

We have conducted four prospective multicenter studies for acute promyelocytic leukemia (APL) using oral 45 mg/m2 all-trans retinoic acid (ATRA) daily. The first three studies were for relapsed/refractory APL, and the fourth study for newly diagnosed APL. In the first study with ATRA alone, 18 (82%) of 22 evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01); < 100/microliters in 17 of 18 CR cases, and > or = 200/microliters in all failure cases. In the second study, if initial leukemia cell counts were more than 200/microliters, chemotherapy with daunorubicin and behenoyl cytarabine was first given, and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. In the third study, if initial leukemia cell counts were more than 200/microliters, chemotherapy was concomitantly given with ATRA, and if during the ATRA therapy leukemia cell counts became more than 1000/microliters, chemotherapy was added. Of 46 evaluable patients, 36 (78%) achieved CR. Patients achieving CR received standard consolidation and maintenance chemotherapy, and the 29-month predicted disease-free survival (DFS) rate is 72% for 41 cases achieving their first CR with ATRA, and 20% for 49 cases achieving their second CR with ATRA. In the fourth study for newly diagnosed APL, if leukocyte counts were more than 3000/microliters, chemotherapy was concomitantly given with ATRA, and if during the ATRA therapy leukemia cell counts became more than 1000/microliters, chemotherapy was added. Of 109 evaluable patients, 97 (89%) achieved CR, and the 19-month predicted event-free survival rate for all patients is 78%, and the DFS rate is 88% for 97 cases achieving CR. ATRA produces a high CR rate in both relapsed/refractory and newly diagnosed APL, and should be incorporated in the first-line therapy of this disease.

Adolescent↗
PubMed1994

[New antitumor drugs for malignant lymphoma: a review].

We summarize here the antitumor activity of newly developed drugs against malignant lymphoma. Irinotecan hydrochloride (CPT-11) showed a CR rate of 15% and an excellent response (CR + PR) rate of 42% in patients with non-Hodgkin's lymphoma who had prior treatment. In patients with ATL, 13% achieved CR and a response rate was 39%. MST-16, a new orally administered bis(2, 6-dioxopiperazine) analogue, showed a CR of 3% and PR of 28% (response rate 31%), among patients with ATL, 9% of 23 patients achieved CR and the response rate was 44%. Phase I studies of fludarabine demonstrated a high response rate of 64%, especially in follicular lymphoma, with a number of patients achieving CR. Subsequent phase II studies demonstrated a response rate of 89% in patients with indolent lymphoma. KRN 8602 was developed in an attempt to improve the clinical efficacy of currently used anthracyclines. KRN 8602 has been shown to produce less cardiotoxicity and alopecia, yet has comparable antitumor effects to ADM, and also has demonstrated an antitumor effect on ADM-resistant tumors. CPT-11 and MST-16 were found effective not only in refractory non-Hodgkin's lymphoma, but also in patients with ATL, which had no standard therapy. Fludarabine has been demonstrated to be a very active drug in indolent lymphoid neoplasms, particularly CLL and low grade lymphoma. These new drugs are expected to overcome malignant lymphoma refractory to treatment thus far.

Antibiotics, Antineoplastic↗
PubMed1994

[Co-operative study of all-trans retinoic acid as a differentiation induction therapy of acute promyelocytic leukemia].

Efficacy and safety of tretinoin (all-trans retinoic acid, ATRA, Ro01-5488) for refractory and relapsed acute promyelocytic leukemia were studied by multi-institutional study in Japan. 22 out of 27 (81.5%) patients with previously untreated who were intolerable to chemotherapy, relapsed and refractory were achieved CR. And 4 out of 11 (36.4%) in relapsed patients who received ATRA remission induction therapy previously responded. Side effects, such as dryness of the lip and skin, headache, increase of triglyceride, beta-lipoprotein and lactate dehydrogenase, were observed in 36 of 41 eligible patients (87.8%) but these were well tolerated. In addition to these, hyperleukocytosis in 4 cases and retinoic acid syndrome in 3 cases were observed. However, all patients were prescribed tretinoin again by adequate management.

Administration, Oral↗
PubMed1994

[New strategy for diagnosis and treatment of acute promyelocytic leukemia with t (15;17)].

All-trans retinoic acid (ATRA)-therapy against acute promyelocytic leukemia (APL) is epoch-making in the sense of the first success in both tumor-differentiation therapy and molecule-targeted therapy. Kouseishou APL-study group performed three clinical studies to refractory APL with ATRA from 1990 to 1993. Complete remission (CR) was obtained in 82%, 88% and 78% of 22, 41 and 46 patients, respectively. Molecular diagnosis of the t (15;17) translocation was possible using Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR).

Chromosomes, Human, Pair 15↗
PubMed1994

[Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies].

A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT-11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma.

Adolescent↗
PubMed1994

[An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with hematological malignancies].

An early phase II study of CPT-11 (irinotecan hydrochloride) was conducted in patients with hematological malignancies by 4 administration regimens in a cooperative study involving 13 institutes in Japan. The overall response rate was 23% (7/30) for non-Hodgkin's lymphoma, 33% (1/3) for Hodgkin's disease, 18% (2/11) for acute lymphoblastic leukemia and 7% (1/15) for acute myelogenous leukemia. One PR was also obtained in a patient with chronic myelogenous leukemia. Among responders, 6 relapsed and refractory malignant lymphomas (ML) and 2 relapsed and refractory acute leukemias (AL) were involved. The response rates in ML with the regimens B (40 mg/m2 for 5 days every 3-4 weeks) and C (40 mg/m2 for 3 days every weeks) were 31% (5/16) and 33% (3/9), respectively. The other regimens (regimen A, 200 mg/m2 once a day every 3-4 weeks and regimen D) resulted in no response. Responses in AL were only observed in regimen D (20 mg/m2 twice a day for 7 days every 3-4 weeks). Major toxicities were leukopenia (91%), nausea/vomiting (74%), diarrhea (73%) and anorexia (64%). The incidence of severe gastrointestinal symptoms was higher in regimen B than regimen C. Further studies are warranted to confirm the effectiveness and safety of CPT-11 against ML and AL. The recommended administration schedule was regimen C for ML and regimen D for AL.

Adolescent↗
PubMed1993

Randomized study of individualized induction therapy with or without vincristine, and of maintenance-intensification therapy between 4 or 12 courses in adult acute myeloid leukemia. AML-87 Study of the Japan Adult Leukemia Study Group.

BACKGROUND: It was assessed whether addition of vincristine (VCR) to remission induction therapy would increase the complete remission (CR) rate, and, secondarily, whether 12 courses of maintenance-intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML). METHODS: A randomized comparison of individualized induction therapy was conducted between daunorubicin, behenoyl cytarabine, 6-mercaptopurine, and prednisolone with or without VCR. After 3 courses of intensive consolidation therapy, maintenance-intensification therapy was randomized to 4 or 12 courses given every 6 weeks. RESULTS: Of 265 patients registered, 252 were evaluable. CR was obtained in 78%; 80% in 205 patients of age younger than 60 years, and 65% in 47 of age 60 years or older. Addition of VCR reduced the CR rate significantly (84% to 70%, P = 0.007). Predicted 4-year survival, continuing CR, and disease-free survival (DFS) rates of 196 CR patients are 45%, 41%, and 35%, respectively. Patients receiving 12 courses of maintenance-intensification showed better DFS. By multivariate analyses, significant factors for achievement of CR were performance status 0 to 2, age younger than 60 years, and no VCR; and those for longer DFS were achievement of CR by one course, age younger than 50 years, and French-American-British (FAB) classification M3 or M5. Among 131 patients randomized to the maintenance, the administration of 12 courses was the most important factor (P = 0.0040) for longer DFS, followed by FAB M3 or M5, and by achievement of CR by one course. CONCLUSIONS: Addition of VCR in remission induction therapy was harmful, and longer intensive maintenance therapy prolonged DFS in adult AML.

Acute Disease↗
PubMed1993

Treatment of adult T-cell leukemia/lymphoma with MST-16, a new oral antitumor drug and a derivative of bis(2,6-dioxopiperazine). The MST-16 Study Group.

BACKGROUND: MST-16, a new orally administered bis(2,6-dioxopiperazine) analogue and an inhibitor of topoisomerase II, was given to 24 patients with adult T-cell leukemia-lymphoma (ATLL) in a Phase I-II multi-institutional cooperative study. METHODS: MST-16 was administered orally daily for 7 days, with courses repeated at intervals of 2-3 weeks in 24 patients. RESULTS: Two complete remissions (CR) and eight partial remissions (PR) were obtained in 23 evaluable patients who received 1200-2800 mg/day of MST-16. Among 13 acute-type ATLL, one CR and five PR were obtained. Among eight lymphoma-type ATLL, two PR were detected. Among two chronic-type ATLL, one CR and one PR occurred. Remissions were obtained at 7-232 days (median, 23 days) and lasted 43-374 days (median, 68 days). The major toxic effects were leukopenia (68%), anemia (52%), thrombocytopenia (35%), and gastrointestinal disorders (22%). CONCLUSIONS: MST-16 was shown to be effective in ATLL, which has no standard therapy. This drug deserves further clinical trials because it shows little cross resistance to currently available antitumor drugs.

Administration, Oral↗
PubMed1993

Treatment of myelodysplastic syndromes with all-trans retinoic acid. Leukemia Study Group of the Ministry of Health and Welfare.

We treated 23 patients with myelodysplastic syndromes (MDS); 2 refractory anemia (RA) with prior therapy, 11 RA with excess of blasts (RAEB), and 10 RAEB in transformation (RAEB-T), with daily oral 45 mg/m2 all-trans retinoic acid (ATRA) in a multiinstitutional prospective study. In two patients with RAEB and one with RAEB-T, a more than 1,000/microL increase of peripheral neutrophil counts was observed with some reduction of blast percentage in the bone marrow 2 to 9 weeks after the start of ATRA. However, the effect was transient and did not last for more than 5 weeks despite the continuation of ATRA therapy. In one other patient with RA, one patient with RAEB, and one patient with RAEB-T, slight increase of hemoglobin levels or reduction of blast percentage in bone marrow was noted. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, abnormal liver function tests, and high serum triglyceridemia. Although ATRA works remarkably as a differentiation therapy in acute promyelocytic leukemia, its effect in MDS included in this study was modest. Further study of this agent alone or in combination may be warranted in less advanced stages of this disease.

Adolescent↗
PubMed1993

Minimal residual disease status in pre-B acute lymphoblastic leukemia patients after chemotherapy and bone marrow transplantation: assessment of the anti-leukemic effects of chemotherapy and BMT.

We prospectively analyzed minimal residual disease (MRD) in four patients with B-cell precursor acute lymphoblastic leukemia who had been in complete remission for more than one year after chemotherapy and allogenic or autologous bone marrow transplantation (BMT). MRD was quantitatively estimated using polymerase chain reaction amplification to detect the complementarity-determining region III of the immunoglobulin heavy chain gene at limiting dilution DNA samples. Our study showed that remission induction chemotherapy reduced at most 2-logs of leukemia cells, and that subsequent consolidation chemotherapy induced further reduction of leukemia cells. In two cases, 10(-5) levels of MRD were detected two months after BMT. However, no MRD was detected four months after BMT. We also showed the effectiveness of ex vivo purging with anti-CALLA monoclonal antibodies which eliminated at least 2-logs of leukemia cells in autologous BMT. Our results suggest that this detection system is useful for assessing the reduction of the original leukemia clone, and that the presence of MRD within three months after BMT is not related to clinical outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Rapid detection of plasma glycocalicin by a latex agglutination test. A useful adjunct in the differential diagnosis of thrombocytopenia.

To aid in the rapid differential diagnosis of thrombocytopenia, the authors developed a latex agglutination test for glycocalicin, a proteolytic fragment of platelet membrane glycoprotein Ib. Plasma glycocalicin determinations were performed for 34 patients with thrombocytopenia. Plasma samples from four patients with aplastic anemia and ten patients with myelodysplastic syndromes, all with glycocalicin levels less than 0.6 mg/L by an enzyme-linked immunosorbent assay, all had negative results by the latex test. In contrast, positive latex agglutination titers were obtained for all 12 patients with idiopathic thrombocytopenic purpura. Eight patients with liver cirrhosis and splenomegaly had elevated levels of plasma glycocalicin, and all of their plasma samples produced agglutination. This latex agglutination test for glycocalicin allows a rapid discrimination of thrombocytopenia caused by impaired platelet production from that caused by increased platelet destruction; thus, it is suitable for use as a screening test in a routine clinical laboratory.

Adolescent↗
PubMed1993

Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia.

We have screened mutations of the N-ras gene at codons 12, 13, and 61 in leukemia cells obtained from 100 patients with acute myeloid leukemia (AML), and found mutated N-ras alleles in 9 patients. We further analyzed the polyclonality of multiple N-ras gene mutations in 4 AML patients. One patient, who had the monoclonal karyotype, t(11;17), had two types of double missense mutations at codons 13 and 61 in the same allele. Each of the remaining three patients, one of whom had t(15;17) with a monoclonal rearrangement of the retinoic acid receptor alpha and PML genes, carried two missense mutations in a relatively small population of leukemia cells. We have demonstrated that multiple clonality of the N-ras gene is occasionally observed in leukemia with a monoclonal karyotype. These findings indicate that the N-ras mutations may not always be characterized simply by an accumulative process and that the activated N-ras gene alone is not sufficient to cause leukemia.

Acute Disease↗
PubMed1993

Molecular heterogeneity of the PML gene rearrangement in acute promyelocytic leukemia: prevalence and clinical significance.

We determined the breakpoints of the RAR-alpha and PML genes in acute promyelocytic leukemia (APL) cells from 40 patients using Southern blot analysis. We also analyzed the relationship between the location of breakpoints, the clinical features of APL and the response to all-trans retinoic acid (ATRA). While the breakpoints of the RAR-alpha gene were consistently within intron 2, we found two major clusters in the breakpoints of the PML gene. The two breakpoint clusters in the PML gene were separated by 10 kb; 5' breakpoints were in intron 3, and 3' breakpoints were around introns 5 and 6. Twenty percent of the patients had 5' breakpoints in the PML gene and 70% had 3' breakpoints. No rearrangement was observed in the remaining 10% of patients in spite of the presence of t(15;17) translocation. There was no relationship between the location of the PML breakpoints, the clinical features at diagnosis and the response to ATRA.

Adolescent↗
PubMed1993

Japanese B cell chronic lymphocytic leukaemia: a cytogenetic and molecular biological study.

Clinical, cytogenetic, and molecular genetic studies were performed to clarify the pathophysiology of Japanese B cell chronic lymphocytic leukaemia (B-CLL), since the incidence of B-CLL in Japan is significantly lower than in western countries. The clinical and laboratory features of 55 Japanese patients with B-CLL in this study did not differ from those of Americans or Europeans with B-CLL. In the chromosome analyses, suitable metaphases with good band quality were obtained from 48 patients (87.2%), of whom 22 patients (45.8%) showed clonal chromosome aberrations and 14 (29.2%) had non-clonal aberrations. Trisomy 12 and abnormalities of 14q and 13q were found in four (18.2%), two (9.1%) and six patients (27.2%), respectively. There were no particular chromosome abnormalities or specific breakpoints in Japanese B-CLL. However, complex karyotype was found in higher incidence than in western countries. In the Southern blot analyses, rearranged band patterns were observed in the major breakpoint region (mbr) of the bcl-2 gene in one case, in the 5'-breakpoint region (5'-bcl-2) in two, and bcl-3 in one. Of the two patients with 5'-bcl-2 rearrangements, one had a normal karyotype and the other had t(2;18)(p12;q21). The incidence of rearrangements of the bcl-1, bcl-2 and bcl-3 genes in Japanese B-CLL was similar to that in western countries. These findings suggest that the biological characteristics of B-CLL in Japan are almost the same as those in western countries, although the incidence of B-CLL in Japan is quite different; this may be related to racial differences, which seem to be an important factor in the development of B-CLL.

Adult↗
PubMed1993

A human monoclonal antibody that detects HLA-A1, A23 and A24 antigens.

We report the production and characterization of a human monoclonal IgM (mu, kappa) antibody recognizing the HLA A1, A23 and A24 antigens. B lymphocytes obtained from a multiparous Japanese woman were transformed in vitro by Epstein-Barr virus, screened with an immune adherence assay, and fused with a murine myeloma cell line, P3-X63-Ag8.653. After subcloning by limiting dilution three times, a stable antibody-secreting hybridoma cell line, 4-35-7, was identified. The culture supernant had a titer of 1:32-64 against each of A1-, A23- and A24-positive lymphocyte panels, and showed complete correlation (r = 1.00) with the A1, A23 and A24 antigens on a lymphocyte panel of 287 unrelated, class I HLA-typed donors by the NIH cytotoxicity assay. Monoclonality of the antibody was ensured by Southern blot analysis of the human immunoglobulin heavy chain gene of 4-35-7. In view of the published data on HLA class I nucleotide sequences, the antibody may recognize an antigeneic determinant including two amino acid residues, Asp-166 and Gly-167, in the alpha 2 helix of the class I molecule that are specific for A1, A23 and A24 so far analyzed.

Animals↗