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Ryuzo Ohno

Publications and source records attributed to Ryuzo Ohno.

At least 19 recordsLinked to original sources
PubMed2006

Clinical features and outcome of T-lineage acute lymphoblastic leukemia in adults: a low initial white blood cell count, as well as a high count predict decreased survival rates.

Although biological and clinical features differ between B-lineage acute lymphoblastic leukemia (ALL) and T-lineage ALL (T-ALL), there have been few reports that focused on the prognosis for T-ALL in adults, primarily due to its rarity. Here, we studied the long-term outcomes and prognostic factors specific for adult T-ALL by combining patient data from the three prospective trials conducted by the Japan Adult Leukemia Study Group (JALSG). Among 559 patients whose immunophenotypes could be evaluated, 87 (15.6%) were identified as T-ALL. Of them, 66 patients (75.8%) achieved complete remission, and relapse occurred in 41 patients. With a median follow-up for surviving patients of 7.5 years, the probability of overall survival was 35.0% at 5 years. Risk factor analysis revealed that serum albumin levels, initial white blood cell (WBC) counts, and age had independent values for predicting survival. For WBC, not only the high-count group (50 x 10(9)l(-1) or higher), but also the low-count group (less than 3 x 10(9)l(-1)) showed a significantly lower survival rates than the intermediate-count group (p=0.0055 and 0.0037, respectively). Although our findings need confirmation, these results will be helpful in the identification of prognostically distinct subgroups within adult T-ALL.

Adolescent↗
PubMed2006

Pharmacokinetics of arsenic species in Japanese patients with relapsed or refractory acute promyelocytic leukemia treated with arsenic trioxide.

PURPOSE: To investigate the pharmacokinetics of arsenic species in Japanese patients with relapsed or refractory acute promyelocytic leukemia (APL) treated with arsenic trioxide (ATO) at a daily dose of 0.15 mg/kg. METHODS: Inorganic arsenic (AsIII and AsV) and the major metabolites monomethylarsonic acid (MAA(V)) and dimethylarsinic acid (DMAA(V)) in plasma and urine collected from 12 Japanese patients were quantified by HPLC/ICP-MS. RESULTS: The plasma concentrations of AsIII and AsV on day 1 reached the similar Cmax (12.4 +/- 8.4 and 10.2 +/- 3.9 ng/ml) immediately after completion of administration followed by a biphasic elimination. The AUC(0-infinity) of AsV was about twice that of AsIII. The appearance of methylated metabolites in the blood was delayed. During the repeated administration, the plasma concentrations of inorganic arsenic reached the steady state. In contrast, the MAA(V) and DMAA(V) concentrations increased in relation to increased administration frequency. The mean total arsenic excretion rate including inorganic arsenic and methylated arsenic was about 20% of daily dose on day 1 and remained at about 60% of daily dose during week 1-4. CONCLUSIONS: This study demonstrates that ATO is metabolized when administered intravenously to APL patients and methylated metabolites are promptly eliminated from the blood and excreted into urine after completion of administration, indicating no measurable accumulation of ATO in the blood.

Adult↗
PubMed2006

Treatment of chronic myeloid leukemia with imatinib mesylate.

Philadelphia (Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML). The translocation forms a chimeric gene, bcr-abl, which generates BCR-ABL. This fusion protein constitutively activate ABL tyrosine kinase and causes CML. Imatinib mesylate is a selective tyrosine kinase inhibitor on ABL, c-Kit and PGDF-receptor, and functions through competitive inhibition at the ATP-binding site of the enzyme, which leads to growth arrest or apoptosis in cells that express BCR-ABL. Imatinib has revolutionized the management of patients with CML, and at a dose of 400 mg daily has become the current standard therapy for newly diagnosed patients with CML even when they have HLA-matched family donors. Although imatinib therapy has only a 5-year history, it is hoped that CML will be cured with this drug and with forthcoming second-generation tyrosine kinase inhibitors as well as by allogeneic stem cell transplantation in patients who have become resistant to these drugs.

Benzamides↗
PubMed2006

Clinicopathological and prognostic characteristics of CD33-positive multiple myeloma.

There have been few reports about the CD33 expression on multiple myeloma (MM) cells so far, showing that only a few patients expressed CD33 homogenously on their MM cells. However, in these reports, neither detailed clinical information nor its prognostic significance was described. Therefore, we analyzed the CD33 expression on MM cells from 63 newly diagnosed patients by flow cytometry and the correlation with other clinical parameters to determine the clinicopathological significance of this molecule. Fourteen (22%) patients were positive for CD33. Of the 14 patients with CD33+ MM, >80% of MM cells were positive in six (9.5%). The CD33+ patients had higher beta 2 microglobulin and lactate dehydrogenase levels and higher incidence of anemia and thrombocytopenia than did CD33- patients. The estimated 3-yr overall survival in CD33+ patients was significantly lower than in the CD33- ones (31% and 50%, respectively, P = 0.042). Especially, mortality within a year from diagnosis in the CD33+patients was higher than that in CD33- patients (43% and 10%, respectively, P = 0.005). Serial evaluation of CD33 expression showed that the amount of CD33 significantly increased after a variety of treatment including melphalan and steroid in individual patients. These results suggest that the CD33 expression might be associated with drug resistance to these conventional agents, and CD33 might be a useful target for the development of new therapeutic agents in MM.

Adult↗
PubMed2006

Method for assessment of viability and morphological changes of bacteria in the early stage of colony formation on a simulated natural environment.

A quantitative analysis of changes in the physiological status of bacterial cells is a fundamental type of study in microbiological research. We devised a method for measuring the viability of bacteria in the early stage of colony formation on a simulated natural environment. In this method, a solid medium containing soil extract was used, and the formation of bacterial microcolonies on a membrane filter was determined by use of a laser scanning cytometer combined with live-dead fluorescent dyes. A polychlorinated biphenyl degrader, Comamonas testosteroni TK102, was used in this study. Surprisingly, approximately 20% of the microcolonies had their growth stopped and eventually died. In the presence of biphenyl, the growth arrest was increased to 50%, and filamentous cells were observed in the colonies. Predicted intermediate metabolites of biphenyl were added to the medium to determine the relationship between the change of viability and the production of metabolites, and the addition of 2,3-dihydroxybiphenyl showed low viability. The arrest was not observed to occur on nutrient-rich medium, suggesting that the change in viability might occur in a nutrient-poor natural condition. The results of this study demonstrated that toxic metabolites of xenobiotics might change cell viability in the natural environment.

Bacteria↗
PubMed2006

Two cases of acute promyelocytic leukemia complicated by torsade de pointes during arsenic trioxide therapy.

We describe 2 patients with acute promyelocytic leukemia (APL) in whom torsade de pointes (TdP) developed during treatment with arsenic trioxide. Patient 1 was a 23-year-old woman with second-relapse APL. Ventricular premature beat bigeminy developed on day 27 of treatment, and episodes of TdP developed on day 28. Patient 2 was a 51-year-old woman with second-relapse APL who had cardiomyopathy due to prior anthracycline treatment. TdP developed on day 17 of treatment. Arsenic trioxide is known to cause electrocardiographic abnormalities, such as ventricular tachycardia and prolongation of QT interval. Patient 1 was given fluconazole as a concomitant drug. Patient 2 had cardiomyopathy and hypokalemia. Careful management is needed during arsenic trioxide therapy because this treatment prolongs the QT interval, possibly inducing episodes of TdP.

Adult↗
PubMed2005

A randomized, postremission comparison of four courses of standard-dose consolidation therapy without maintenance therapy versus three courses of standard-dose consolidation with maintenance therapy in adults with acute myeloid leukemia: the Japan Adult Leukemia Study Group AML 97 Study.

BACKGROUND: A major concern in the treatment of patients with acute myeloid leukemia (AML) is how to prevent disease recurrences. Although intensive consolidation therapy has proven useful, the effectiveness of maintenance therapy remains controversial. METHODS: Seven hundred eighty-nine patients ages 15-64 (median: 45 yrs) with de novo AML received induction therapy, which consisted of cytosine arabinoside (at a dose of 100 mg/m(2) on Days 1-7) and idarubicin (at a dose of 12 mg/m(2) on Days 1-3). The patients who achieved complete remission (CR) were then randomized into groups that received either four courses of standard-dose consolidation therapy without maintenance (Arm A) or three courses of standard-dose consolidation and six courses of maintenance therapy (Arm B). RESULTS: In total, 78.7% of patients achieved CR. The 5-year overall survival (OS) rate for the 789 eligible patients was 46.9%, and the disease-free survival (DFS) rate for the 621 patients who achieved CR was 32.9%. The 5-year OS rate for Arm A was 52.4%, and 58.4% for Arm B (P = 0.599). The 5-year DFS rate for the patients who achieved CR was 35.8% in Arm A and 30.4% in Arm B (P = 0.543). In analyzing the data according to the risk groups, no statistical difference was observed either in the 5-year OS rate or in the 5-year DFS rate between the 2 arms. CONCLUSIONS: In the current study, the Japan Adult Leukemia Study Group's conventional postremission therapy (three courses of standard-dose consolidation and six courses of maintenance therapy) was replaced successfully by a shorter duration of four courses of standard-dose consolidation therapy without the need for additional maintenance therapy.

Adolescent↗
PubMed2005

High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group.

PURPOSE: A novel therapeutic approach is urgently needed for BCR-ABL-positive acute lymphoblastic leukemia (ALL). In this study, we assessed the efficacy and feasibility of chemotherapy combined with imatinib. PATIENTS AND METHODS: A phase II study of imatinib-combined chemotherapy was conducted for newly diagnosed BCR-ABL-positive ALL in adults. Eighty patients were entered into the trial between September 2002 and January 2005. RESULTS: Remission induction therapy resulted in complete remission (CR) in 77 patients (96.2%), resistant disease in one patient, and early death in two patients, as well as polymerase chain reaction negativity of bone marrow in 71.3%. The profile and incidence of severe toxicity were not different from those associated with our historic chemotherapy-alone regimen. Relapse occurred in 20 patients after median CR duration of 5.2 months. Allogeneic hematopoietic stem-cell transplantation (HSCT) was performed for 49 patients, 39 of whom underwent transplantation during their first CR. The 1-year event-free and overall survival (OS) rates were estimated to be 60.0%, and 76.1%, respectively, which were significantly better than those for our historic controls treated with chemotherapy alone (P < .0001 for both). Among the current trial patients, the probability for OS at 1 year was 73.3% for those who underwent allogeneic HSCT, and 84.8% for those who did not. CONCLUSION: Our results demonstrated that imatinib-combined regimen is effective and feasible for newly diagnosed BCR-ABL-positive ALL. Despite a relatively short period of observation, a major potential of this treatment is recognized. Longer follow-up is required to determine its overall effect on survival.

Adolescent↗
PubMed2005

Molecular target-based treatment of human cancer: summary of the 10th international conference on differentiation therapy.

The 10th International Conference on Differentiation Therapy was held between April 29 and May 3, 2004, in Shanghai, China. In the tradition of previous conferences from this series, which have been held biannually since the first meeting organized 20 years ago by Samuel Waxman and Giovanni Rossi in Sardinia, the organizers of the 10th International Conference on Differentiation Therapy aimed to gather basic and clinical cancer investigators in a setting of plenary sessions, workshops, and poster presentations to maximize the effective exchange of information and foster the establishment of collaborative interactions. Approximately 300 scientists attended the meeting with a mission to discuss targeted approaches to cancer treatment, which stem from our understanding of basic biological processes and the mechanisms of their deregulation during tumorigenesis.

Apoptosis↗
PubMed2005

Arsenic trioxide therapy in relapsed or refractory Japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies.

Recently, arsenic trioxide (ATO) has been proved to induce complete remission (CR) at a high rate in patients with acute promyelocytic leukemia (APL). We prospectively investigated the safety and efficacy of ATO therapy in patients with relapsed and refractory APL and examined the duration of CR and the postremission therapies. Initially, 0.15 mg/kg ATO was administered until bone marrow remission to a maximum of 60 days. After the patient achieved CR, 1 additional ATO course at the same dosage was administered for 25 days. Of 34 patients, 31 (91%) achieved CR. PML-RAR3 messenger RNA was not detected in the bone marrow of 18 (72%) of the 25 patients evaluated by reverse transcriptase-polymerase chain reaction analysis. At a median follow-up of 30 months, the estimated 2-year overall survival rate was 56%, and the estimated 2-year event-free survival rate was 17%. During the ATO therapy, QTc prolongation was observed in most cases. Fifteen patients developed ventricular tachycardia, and 1 of them showed torsades de pointes. Other adverse events were nausea, water retention, APL differentiation syndrome, skin eruption, liver dysfunction, and peripheral neuropathy, all of which were quite tolerable. ATO therapy was remarkably effective for relapsed APL; however, postremission therapies were necessary to maintain a durable remission.

Adolescent↗
PubMed2005

Two patients with all-trans retinoic acid-resistant acute promyelocytic leukemia treated successfully with gemtuzumab ozogamicin as a single agent.

Acute promyelocytic leukemia (APL) cells express a considerable level of CD33, which is the target of gemtuzumab ozogamicin (GO), and a significantly lower level of P-glycoprotein (P-gp). Therefore, GO is predicted to be a successful treatment for APL. In this article, we report on the GO treatment of 2 patients with APL, who had fully relapsed after induction therapy with all-trans retinoic acid (ATRA) following chemotherapy. Both patients had relapsed 3 times and were resistant to reinduction therapy with ATRA. GO (9 mg/m2) was administered on days 1 and 15. After GO treatment, both patients achieved complete hematologic and molecular remission. GO may be another promising agent for the treatment of ATRA-resistant relapsed APL when given as salvage chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Delayed recovery of normal hematopoiesis in arsenic trioxide treatment of acute promyelocytic leukemia: a comparison to all-trans retinoic acid treatment.

OBJECTIVE: To examine laboratory data including total blood cell count, leukocyte morphology and coagulation parameters during treatment for acute promyelocytic leukemia (APL) at a single institute, and compare the precise differences between all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) treatment. PATIENTS AND METHODS: Sixteen patients with APL who were treated with ATRA or As2O3 alone and achieved complete remission (CR) were analyzed. ATRA 45 mg/m2/day was given orally until CR. As2O3 0.15 mg/kg/day was given intravenously until leukemic blasts and promyelocytes were eliminated from the bone marrow. RESULTS: All 7 patients in the ATRA-treated group were primary cases and all 9 patients in the As2O3-treated group were relapsed cases after the achievement of CR with the ATRA. There was no difference in the data before treatment between these two groups. The duration of leukocytopenia and neutropenia during As2O3 treatment was significantly longer than those of ATRA treatment. The nadir of leukocyte and neutrophil counts was observed later in the As2O3-treated group. Terminal neutrophil differentiation was observed more obviously in the ATRA-treated group. The red blood cell count and hemoglobin concentration decreased significantly at the end of As2O3 treatment and were lower than those of ATRA treatment. Platelets recovered earlier in the ATRA-treated group. Coagulation parameters were not significantly changed between the two groups. CONCLUSION: In comparison with ATRA treatment, the recovery of several components in the peripheral blood cells was delayed in As2O3 treatment. Therefore we should pay more and longer attention in As2O3 treatment.

Antineoplastic Agents↗
PubMed2004

Disease-related potential of mutations in transcriptional cofactors CREB-binding protein and p300 in leukemias.

CREB-binding protein (CBP) and highly related p300 protein are transcriptional co-activators that play an essential role in chromatin remodeling through histone acetyltransferase activity and interaction with other transcriptional regulators. In this study, various hematological malignancies, including nine cell lines and 45 clinical samples (32 acute myeloid leukemias (AML), nine acute lymphoblastic leukemias (ALL), two cases of myelodysplastic syndrome (MDS), one multiple myeloma, and one chronic myelogenous leukemia in blast crisis), were examined to ask whether mutation of the CBP and p300 genes could be involved in leukemogenesis. The answer was approached by employing the reverse transcription-polymerase chain reaction and single-strand conformation polymorphism (RT-PCR/SSCP) technique and subsequent sequence analysis. A T-lymphoblastic cell line, CEM had an in-frame 21-base-pair deletion within the bromodomain of its p300 cDNA. Genomic DNA analysis revealed aberrant splicing caused by mutation of the acceptor site of intron 17 from ag to gg, which should interfere with catalytic step II of the pre-mRNA splicing reaction. In 1 MDS patient, a missense mutation was detected, which caused a replacement from Ser to Gly at codon 507 of p300. This is the first report of CBP/p300 mutations in leukemias, which might be relatively rare but nonetheless contribute to pathogenesis in some fraction of cases.

Acetyltransferases↗
PubMed2004

Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia.

The outcome for adult patients with BCR-ABL-positive acute lymphoblastic leukemia (ALL) remains dismal and long-term survival can hardly be achieved except by allogeneic hematopoietic stem cell transplantation (HSCT). The Japan Adult Leukemia Study Group (JALSG) has recently started a phase 2 trial with intensive chemotherapy and imatinib for newly diagnosed BCR-AB-positive ALL patients, and we present here the interim results for the first 24 patients. All patients except one case of early death (96%) attained complete remission (CR) after a single course of remission induction therapy. Polymerase chain reaction (PCR) negativity was achieved in 28% of the patients on day 28, in 50% on day 63, and in up to 78% during the follow-up period. The toxicity profile was almost similar to that with chemotherapy alone. As a result, 15 patients (63%) could receive an allogeneic HSC transplant during their first CR. Although the number of patients is small and the observation period is too short, the combination therapy is very promising and produces high-quality CR for most newly diagnosed patients with BCR-ABL-positive ALL. This is especially useful because it provides the patients with a better chance to receive an allogeneic HSC transplant.

Adolescent↗
PubMed2004

Current antimicrobial usage for the management of infections in leukemic patients in Japan: results of a survey.

We report the findings of a questionnaire distributed by the Committee of Supportive Care of the Japan Adult Leukemia Study Group to 196 hospitals throughout Japan. For antimicrobial prophylaxis, the oral quinolones are prescribed by 38% of physicians and polymixin B by 31%. For antifungal prophylaxis, amphotericin B is prescribed by 42% of physicians and fluconazole by 41%. Febrile neutropenia is empirically treated with cephalosporin or carbapenem monotherapy by 35% of physicians. Overall, dual therapy (i.e., an aminoglycoside plus a cephalosporin, a carbapenem, or an antipseudomonal penicillin) is prescribed by 50% of physicians. When response to initial empirical therapy does not occur after 3-4 days, 51% of physicians add an antifungal agent; fluconazole is preferred to amphotericin B (prescribed by 66% vs. 28% of physicians). For the treatment of fungemia due to Candida albicans, fluconazole was prescribed by 59% of physicians in cases of stable disease and amphotericin B was prescribed by 57% of physicians in cases of unstable disease. Amphotericin B is selected to treat invasive aspergillosis, but a dose of 0.5-0.7 mg/kg, inadequate for this disease, is prescribed by 44% of physicians. Granulocyte colony-stimulating factor is prescribed to treat patients with acute myelogenous leukemia who have life-threatening infections (27% of physicians) or who have clinically or microbiologically documented infections (26% of physicians).

Anti-Bacterial Agents↗
PubMed2004

Antimicrobial prophylaxis in febrile neutropenia.

Antibiotics generally considered for antibacterial prophylaxis for immunosuppressed patients are trimethoprim-sulfamethoxazole and the quinolones. Trimethoprim-sulfamethoxazole can significantly reduce infections and is highly effective in preventing pneumonia due to Pneumocystis carinii. However, it can cause sulfonamide-related reactions, myelosuppression, oral candidiasis, and development of bacterial resistance, and it lacks activity against Pseudomonas aeruginosa. Quinolones can reduce the occurrence of fever and infections in patients with neutropenia but do not provide adequate coverage against gram-positive bacteria, and inappropriate use can induce resistance among gram-negative organisms. Routine antibacterial prophylaxis is not recommended for patients likely to develop neutropenia. Antifungal prophylaxis is appropriate in settings in which fungal infections are frequent. Fluconazole is recommended for patients who are to undergo hematopoietic stem cell transplantation; it can be considered for elderly patients with acute leukemia who are to receive intensive chemotherapy. Itraconazole can also be used. Prophylaxis with antiviral agents is generally not indicated; however, it should be given to hematopoietic stem cell transplant recipients.

Antibiotic Prophylaxis↗
PubMed2004

Deletion 6p23 and add(11)(p15) leading to NUP98 translocation in a case of therapy-related atypical chronic myelocytic leukemia transforming to acute myelocytic leukemia.

A NUP98 gene translocation occurring with a del(6p23) and an add(11)(p15) was determined in a 61-year-old patient with therapy-related atypical chronic myelocytic leukemia after complete remission from acute promyelocytic leukemia that eventually underwent clonal evolution and transformed to CD56-positive acute myelocytic leukemia (French-American-British classification M0). Precise chromosome analysis by G-banding, spectral karyotyping analysis, and dual-color fluorescence in situ hybridization showed this abnormality as 46,XY,del(6)(p23),add(p15). ish del(6)(NUP98-,D6Z1+),der(7)(NUP98+,D7Z1+),der(11)(NUP98+,D11Z1). A split signal of NUP98 was observed in 68.4% of the 117 cells analyzed, which clearly indicated that the NUP98 partially translocated to chromosome 7. However, the potential fusion partner of the NUP98 was not HOX family or DEK. The fusion gene has not been found by a differential display method. The significance of simultaneously combined del(6)(p23), which also has been reported with secondary leukemogenesis, has not been elucidated. Additional karyotype abnormalities evolved increasingly, and leukocytosis with blasts with more complex karyotypic abnormalities appeared 5 months later. Careful and continuous analysis of karyotype change clarified the process of the clonal evolution after NUP98 translocation. Further investigation of molecular characterization of this NUP98 translocation and interaction with 6p23 abnormalities might be worthwhile for understanding leukemogenesis.

Chromosome Deletion↗