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Michinori Ogura

Publications and source records attributed to Michinori Ogura.

At least 19 recordsLinked to original sources
PubMed2006

Once-weekly epoetin-beta improves hemoglobin levels in cancer patients with chemotherapy-induced anemia: A randomized, double-blind, dose-finding study.

OBJECTIVE: To determine a recommended dose of once-weekly epoetin-beta administration for anemic cancer patients receiving myelosuppressive chemotherapy, we conducted a multicenter, randomized, double-blind trial. METHODS: A total of 86 patients with malignant lymphoma or lung cancer who received chemotherapy containing platinum, taxanes or anthracyclines were enrolled in the study. Patients were randomly assigned into groups that received three dose levels of epoetin-beta (9000, 18,000 or 36,000 IU) administered subcutaneously once a week for 12 weeks. The primary endpoint was change in hemoglobin, while the secondary endpoints were quality of life (QOL) assessed by Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire and transfusion requirements. RESULTS: Among the 69 patients (per protocol set population) assessable for efficacy, hemoglobin level change in the 36,000 IU group was significantly greater than that in the 9000 IU group (1.75 +/- 2.15 versus 0.04 +/- 1.98 g/dl; P = 0.009), and a significant dose-response relationship was observed for the change in hemoglobin level (P = 0.003). Although changes in FACT-An Total Fatigue subscale (Fatigue subscale) scores were similar for the three dosage groups, there was a statistically significant correlation (r = 0.435, P < 0.001) between the change in hemoglobin levels and the change in Fatigue subscale scores. The proportion of transfused patients was significantly smaller in the 36 000 IU group compared with that in the 9000 IU group (P = 0.022, not adjusted for pre-study transfusions). The incidence of adverse events was similar in the three dosage groups. CONCLUSIONS: Once-weekly epoetin-beta 36,000 IU for 12 weeks was well tolerated and significantly increased hemoglobin levels in anemic cancer patients receiving chemotherapy.

Adult↗
PubMed2006

Randomized phase II study of concurrent and sequential rituximab and CHOP chemotherapy in untreated indolent B-cell lymphoma.

CHOP combined with rituximab (R-CHOP) is regarded as one of the most effective treatments for indolent B-cell non-Hodgkin lymphoma (B-NHL), however, its optimal combination schedule remains unknown. We performed a randomized phase II study to explore a more promising schedule in untreated, advanced indolent B-NHL. Patients were randomized to receive either six courses of CHOP concurrently with rituximab (Arm C), or six courses of CHOP followed by six courses of weekly rituximab (Arm S). A total of 69 patients received the concurrent (n=34) or sequential (n=35) regimen. Overall response rate (ORR) in Arm C was 94% (95% confidence interval [CI], 79 to 99), including a 66% complete response (CR) compared with 97% (95% CI, 85-100), including a 68% CR in Arm S. Patients in Arm C experienced more grade 4 neutropenia (85%versus 70%) and experienced more grade 3 or greater non-hematological toxicities (21%versus 12%). Both arms were tolerated well. With a median follow-up of 28.2 months, the median progression-free survival (PFS) time was 34.2 months in Arm C, and was not reached in Arm S. R-CHOP is highly effective in untreated indolent B-NHL, either concurrent or in a sequential combination. Both combination schedules deserve further investigation.

Adult↗
PubMed2005

Phase II study of oral fludarabine phosphate in relapsed indolent B-Cell non-Hodgkin's lymphoma.

PURPOSE: Although intravenous (IV) fludarabine phosphate is effective against indolent B-cell non-Hodgkin's lymphoma (B-NHL), IV administration for 3 to 5 consecutive days is inconvenient in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine phosphate in patients with indolent B-NHL, we conducted a multicenter phase II study. PATIENTS AND METHODS: Patients with relapsed indolent B-NHL received fludarabine phosphate tablets orally once daily on days 1 through 5 every 28 days for three to six cycles. The efficacy was separately analyzed in a mantle-cell lymphoma (MCL) cohort and indolent B-NHL except for MCL (IL) cohort. The primary end point was the overall response rate (ORR). RESULTS: Fifty-two patients, including 46 in the IL cohort (41 with follicular lymphoma) and six in the MCL cohort, were registered, and all patients were eligible. Forty-one patients (79%) had received rituximab as prior therapy. In the IL cohort, the ORR and complete response rate were 65% (30 of 46 patients; 95% CI, 50% to 79%) and 30% (14 of 46 patients; 95% CI, 18% to 46%), respectively. One of six patients with MCL achieved a partial response. The median times to treatment failure for the 46 patients in the IL cohort and for the six patients in the MCL cohort were 8.6 and 6.1 months, respectively. Hematologic toxicities, including grade 4 neutropenia (37%), were the most frequent toxicities, and nonhematologic toxicities were mild. CONCLUSION: Oral fludarabine phosphate is highly effective in patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab and is more convenient than the IV formulation.

Administration, Oral↗
PubMed2005

CD56/NCAM-positive Langerhans cell sarcoma: a clinicopathologic study of 4 cases.

This report concerns the clinicopathologic features of 4 patients with CD56/neural cell adhesion molecule (NCAM)-positive Langerhans cell sarcoma (LCS). Three of the patients were elderly, between 59 and 62 years of age at presentation, and the other was 35 years old. The presenting symptoms included fever, bone pain, and weakness. The patients shared some clinical findings, such as multiorgan involvement of lymph nodes, skin, lung, bone marrow, and spleen. LCS carries a poor prognosis, and 3 of the patients died of the disease within several years of presentation despite multiagent chemotherapy and radiotherapy. Of special interest is that all of the cases showed CD56 expression on the tumor cells in addition to expression of CD1a, S100beta, and langerin, the presence of which suggests derivation from Langerhans cells. For control, CD56 was also examined in 8 cases of Langerhans cell histiocytosis (LCH), a single-system unifocal or multifocal disease, and the results of staining of the tumor cells were negative. Our findings indicated that CD56 may be a clinically relevant biologic marker for predicting an intractable course of Langerhans cell neoplasms, although it is often difficult to draw a definite morphologically-based distinction between LCS and LCH.

Adult↗
PubMed2005

Isolation and transplantation of highly purified autologous peripheral CD34+progenitor cells: purging efficacy, hematopoietic reconstitution following high dose chemotherapy in patients with breast cancer: results of a feasibility study in Japan.

BACKGROUND: High-dose chemotherapy with autologous stem cell support may have some therapeutic impact on certain groups of the patients with advanced breast cancer(BRCA). Since stem cell contamination by tumor cells might contribute to relapse, development of a tumor cell purging technique would improve the clinical outcome. The present study was undertaken to evaluate the purging efficacy of autologous mobilized CD34+peripheral stem cells in patients with breast cancer (BRCA) in an advanced stage or relapse. METHODS: CD34+cells were selected from autologous peripheral blood stem cells (PBSC) using a clinical scale of magnetic-activated cell sorting system (CliniMACS), followed by high-dose chemotherapy with transplantation of CD34+ selected cells. Amplification of cytokeratin 19 (CK19) and 20 (CK20) gene in leukapheresis products were measured to evaluate the performance of tumor cell elimination. RESULTS: Seven patients were entered into this study. After leukopheresis, 1 patient was dropped form this study due to poor mobilization. Among 6 patient, a total of 8 CD34+ selection was performed. The median purity and recovery rate of the CD34+ cells post selection was 85.1% (range 62.5-98.1%) and 74.2% (range 50.2-90.2%), respectively. After isolation of CD34+cells, the elimination rate in the logarithmic transformation of CK19 was 2.77 log, and that of CK20 were 2.43 log and 2.53 log. In 4 patients, high-dose chemotherapy was performed, followed by the transplantation of the isolated CD34+cells. Rapid neutrophil recovery, as well as platelet recovery was seen with a median time to reach 0.5 x 109/l neutrophils of 9 days(range 8-9), and 20 x 109/l platelets of 12 days (range 10-13). There was no treatment related death and no serious adverse events directly associated with the selection procedure or infusion of selected cells. CONCLUSIONS: The present study demonstrated that the CliniMACS system is a highly effective positive selection method and that a high purging efficacy could be obtained without compromising the hematopoietic reconstitution capacity of the graft in BRCA patients undergoing high-dose chemotherapy.

Antigens, CD34↗
PubMed2005

[Progress in therapeutic strategy for malignant lymphoma].

Dramatic progress in therapeutic strategy for malignant lymphoma has been made during recent few years because of the development of new drugs or new therapeutic modalities such as rituximab, purine analogue, purged autologous PBSCT or allogeneic PBSCT by the reduced intensity technique. Rituximab in particular changed the golden standard therapy for previously untreated patients with diffuse large B-cell lymphoma from CHOP therapy to rituximab-CHOP (R-CHOP) therapy in all risk groups. In follicular lymphoma with no treatment strategies associated with curative potential and median survival in the range of 8 to 13 years, prolonged progression-free survival has been reported by maintenance-use of rituximab, R-CHOP therapy, purine analog, in vivo purged auto-PBSCT by rituximab, or reduced intensity stem-cell transplantation (RIST), although no curable survival benefit has yet been demonstrated by any strategies. Short courses (4 courses) of ABVD followed by involved field irradiation therapy (IFRT) for localized early-stage Hodgkin lymphoma (HL), and full courses (6-8 courses) of ABVD (d) for advanced stage HL are the golden standard therapy for HL, respectively. Clinical trials of new therapies with more efficacy and less toxicity have been undertaken.

Algorithms↗
PubMed2005

[Tumor markers in malignant lymphoma].

For malignant lymphoma, there is no highly sensitive or specific tumor marker for diagnosis. However, some tumor markers such as cell surface marker or karyotypic analysis are useful for diagnosis combined with other clinical and pathological information. International Prognostic Index (IPI), Follicular Lymphoma International Prognostic Index (FLIPI), and International Prognostic Score (IPS) are useful to predict prognosis, and utilized to decide therapeutic strategy of aggressive non-Hodgkin's lymphoma (NHL), follicular lymphoma and Hodgkin's lymphoma, respectively. Non-specific biological markers such as soluble interleukin-2 receptor (sIL-2 R) are utilized to evaluate therapeutic effect. In this paper, we describe about the significance of these tumor markers in malignant lymphoma.

Biomarkers, Tumor↗
PubMed2004

Methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms and reduced risk of malignant lymphoma.

Folate and methionine are important nutrients in the "one-carbon" metabolism that is closely associated with DNA synthesis and DNA methylation. Genetic variation in these pathways may change susceptibility to cancer development. We have previously reported associations between lymphoma risk and germline polymorphisms in genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase (MTR A2756G), finding the genotype other than the MTHFR 677CC/1298AA to confer a half-risk compared to the MTHFR 677CC/1298AA and a 3-fold higher risk with the MTR GG genotype than the AA/AG genotypes. To confirm the association and explore the histological difference, we extended the previous case series. A case-control study was conducted in Japan with a total of 372 lymphoma cases and 500 noncancer controls examined for genotypes. The relative risks were estimated by unconditional logistic regression analysis. In overall analyses, the age-sex adjusted odds ratio (OR) for the subjects harboring MTHFR 677T or 1298C alleles relative to 677CC/1298AA genotype was 0.58 (95% confidence interval: 0.41-0.83, P = 0.002). The MTR GG genotype showed an OR of 1.75 (0.87-3.52, P = 0.114). These findings were validated in separate analyses of the 273 new incident cases. Subgroup analyses according to histological subtype [diffuse large B-cell lymphoma (DLB), follicular lymphoma (FL), low-grade lymphoma of mucosa associated lymphoid tissue (MALT), and others] illustrated similar associations with certain exceptions for FL and MALT. Our data showed an association between the MTHFR polymorphisms and malignant lymphoma risk for all histological subtypes, although the extent of contribution of these polymorphisms may differ somewhat with histological subtype. Lack of association with MTR polymorphism was also confirmed.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2004

Polymorphisms of p53 Arg72Pro, p73 G4C14-to-A4T14 at exon 2 and p21 Ser31Arg and the risk of non-Hodgkin's lymphoma in Japanese.

We hypothesized that the polymorphisms in the two p53 family genes (p53 Arg72Pro and p73 G4C14-to-A4T14 at exon 2 (G4A)) and p21 Ser31Arg polymorphism might modulate the risk of non-Hodgkin's lymphoma, and conducted a hospital-based prevalent case control study at Aichi Cancer Center Hospital to clarify the association. Risk estimation for each genotype by the unconditional logistic model demonstrated the possible association between the p53 Pro72 allele and the risk of non-Hodgkin's lymphoma in Japanese population (OR = 1.59; 95% CI, 0.99-2.57, P = 0.057), although no other significant association was observed. The analyses of statistical interactions between these three polymorphisms (p73 G4A, p53 Arg72Pro and p21 Ser31Arg polymorphisms) revealed the marginally significant OR for interaction between p53 Arg72Pro and p73 G4A polymorphisms (OR = 2.54; 95% CI, 0.97 6.62, P = 0.057). When those without p53 Pro72 and p73 A4T14 alleles were defined as a reference, those with p53 Pro72 and p73 A4T14 alleles demonstrated a significantly higher OR (2.08; 95% CI, 1.11-3.90, P = 0.023). Further examination with a sufficiently larger population and other ethnicities are required to confirm our findings.

Adult↗
PubMed2004

Efficacy and safety of imatinib mesylate for patients in the first chronic phase of chronic myeloid leukemia: results of a Japanese phase II clinical study.

Imatinib mesylate is a relatively new drug that targets the BCR-ABL chimeric protein, the molecular basis of chronic myeloid leukemia (CML). A phase II clinical trial in 39 Japanese patients in the first chronic phase of CML was conducted with imatinib mesylate at a dose of 400 mg/day. Hematologic complete response was obtained in 92.3% of the patients, complete cytogenetic response (CR) was obtained in 43.6%, and major partial CR was obtained in 20.5% of the patients. Although 29 of 39 patients required an adjustment of dosing because of grade 3 or 4 adverse events, most of the events were reversible, and 25 of the 29 patients were able to resume therapy. Between day 15 and day 35, grade 3 or 4 neutropenia and/or leukocytopenia occurred in 13 patients, and grade 3 thrombocytopenia occurred in 5 patients. Overall, nonhematologic grade 3 adverse events occurred in 28.2% of the patients. These data support the use of imatinib mesylate as the treatment of choice for chronic-phase CML patients.

Adult↗
PubMed2004

Durable response but prolonged cytopenia after cladribine treatment in relapsed patients with indolent non-Hodgkin's lymphomas: results of a Japanese phase II study.

We conducted a phase II study to evaluate the efficacy and safety of cladribine (2-chlorodeoxyadenosine [2-CdA]) for patients with refractory or relapsed indolent B-cell lymphoma or mycosis fungoides. Forty-five patients were enrolled, and 43 patients, including 34 with follicular lymphoma, were eligible. 2-CdA was given by continuous intravenous infusion at a dose of 0.09 mg/kg daily for 7 consecutive days, and this schedule was repeated every 4 weeks up to a maximum of 6 cycles. The overall and complete response rates were 58.1% (25/43; 90% confidence interval, 44.5%-70.9%) and 14.0% (6/43), respectively. The disease progression-free proportions of all 43 eligible and all 25 responding patients at 2 years were 30.3% and 48.1%, respectively. Neutropenia and thrombocytopenia of grade 3 or 4 were observed in 53.3% and 37.8% of patients, respectively, with prolonged cytopenia observed in patients with increased numbers of treatment cycles. Nonhematologic toxicities of grade 3 or greater included diarrhea, arrhythmia, malaise, and gastrointestinal bleeding in 1 patient each, an increase in glutamic-pyruvic transaminase level in 2 patients, and infection in 5 patients. Two treatment-related deaths were observed. Four patients developed myelodysplastic syndrome (MDS) at 13 months to 2 years after completion of the 2-CdA treatments. 2-CdA is an active agent with acceptable toxicity for refractory or relapsed indolent lymphoma; however, prolonged myelosuppression and the potential development of MDS should be carefully monitored.

Adult↗
PubMed2004

A randomized controlled trial investigating the survival benefit of dose-intensified multidrug combination chemotherapy (LSG9) for intermediate- or high-grade non-Hodgkin's lymphoma: Japan Clinical Oncology Group Study 9002.

The effect of enhancing the dose intensity (DI) of the key drugs in multidrug combination chemotherapy for malignant lymphoma is uncertain. We investigated the survival benefit of dose-intensified multidrug combination chemotherapy for intermediate- or high-grade non-Hodgkin's lymphoma (NHL). Patients without any prior chemotherapy were randomly assigned either to dose-intensified multidrug combination chemotherapy, LSG9 (VEPA-B/FEPP-AB/M-FEPA, treated 3 times every 10 weeks for 28 weeks total), or to control-arm combination chemotherapy, mLSG4 (VEPA-B/FEPP-B/M-FEPA, treated 4 times every 14 weeks for 54 weeks total). The planned DI of doxorubicin and cyclophosphamide were 1.96 and 1.47 times higher, respectively, in LSG9 than in mLSG4. Overall survival, complete response (CR) rate, and toxicities were evaluated. The 447 patients (230 for LSG9 and 217 for mLSG4) were enrolled between February 1991 and March 1995. The 5-year overall survival rates were 56.8% for LSG9 patients and 55.1% for mLSG4 patients (log-rank P = .42). The rates for CR plus uncertain CR were 70.0% for LSG9 and 64.5% for mLSG4. The toxicities of both regimens were similar and tolerable. The median actual DI of doxorubicin and cyclophosphamide were 1.56 and 1.17 times higher, respectively, in LSG9 than in mLSG4. Compared with the control regimen mLSG4, the dose-intensified regimen LSG9 did not show significant survival benefit. An increase in the DI of doxorubicin in multidrug combination chemotherapy did not improve the survival of patients with intermediate- or high-grade NHL.

Adolescent↗
PubMed2004

[Hairy cell leukemia therapy by cladribine].

Cladribine (2-chlorodeoxyadenosine: 2-CdA), a purine nucleoside analog, is a safe and very effective treatment for patients with hairy cell leukemia (HCL). 2-CdA was approved in USA and Japan, and is first-choice drug against symptomatic HCL. It is administered at a dose of 0.09 mg/kg daily as a continuous intravenous infusion over 7 days. Structure, mechanism of action, clinical data of efficacy and safety of 2-CdA, and indications for therapy for HCL are reviewed.

Antineoplastic Agents↗
PubMed2003

Pilot phase I/II study of new salvage therapy (CHASE) for refractory or relapsed malignant lymphoma.

A pilot phase I/II study was conducted as a single-institute trial for evaluation of the feasibility and efficacy of a new salvage chemotherapy, CHASE, for patients with refractory or relapsed lymphoma . The CHASE regimen, consisting of cyclophosphamide, cytosine arabinoside, etoposide, and dexamethasone, was administered every 3 weeks in a maximum of 5 courses. A total of 16 patients were eligible and registered for this study. Myelosuppression was the major toxicity. Although grade 4 leukopenia and grade 3 thrombocytopenia were identified in 15 and 16 patients, respectively, duration of the nadir was brief (median, 3 days). Nonhematological grade 4 toxicity was not observed, and transient elevations of bilirubin and grade 3 aspartate aminotransferase/alanine aminotransferase (AST/ALT) were observed in 2 and 3 courses, respectively, in a total of 57 courses. Complete and partial response rates were 71.4% (10/14) and 7.1% (1/14), respectively. The median percentage of maximal CD34+ cells was 6.1% on day 15, and a median number of 1.88 x 10(6) CD34+ cells/kg per apheresis were obtained. Thirteen patients received high-dose chemoradiotherapy followed by autologous peripheral blood stem cell transplantation. With a median follow-up time of 36 months from the start of CHASE, the overall survival rate for the 16 patients was 66.6%. These results indicated that CHASE is a safe and effective salvage regimen for malignant lymphoma, has sufficient mobilizing effect on peripheral blood stem cells, and warrants further phase II study.

Adult↗
PubMed2003

Polymorphism in the hMSH2 gene (gIVS 12-6T-->C) and risk of non-Hodgkin lymphoma in a Japanese population.

We conducted a hospital-based prevalent case-control study in a Japanese population (cases=103, controls=487) to ascertain the previous report about the association between the polymorphism in exon 13 of the hMSH2 gene (gIVS 12-6T-->C) and the risk of non-Hodgkin lymphoma in an Ecuadorian population. When the TT genotype was defined as the reference, none of the CT genotypes (OR=1.52; 95% CI, 0.97-2.37), CC genotypes (OR=1.06, 95% CI, 0.44-2.54), or CT and CC genotypes combined together (OR=1.44, 95% CI, 0.94-2.23) demonstrated significant OR. Further investigations with sufficiently larger populations and in other ethnicities are required to verify this association.

Adenosine Triphosphatases↗
PubMed2003

Phenotypic analysis of peripheral T/NK cell lymphoma: study of 408 Japanese cases with special reference to their anatomical sites.

The World Health Organization (WHO) classification of malignant lymphoma presented a list of disease entities well defined by clinical, immunological and genetic features. Therefore, the current diagnosis of peripheral T/NK-cell lymphomas (PTNKLs) essentially requires the inclusion of anatomical sites of disease and phenotypical features. We analyzed 408 Japanese cases of PTNKLs in order to clarify the relationship between anatomical sites of disease and phenotypical features and to translate the functional subsets of T and NK cells into their diagnoses for further understanding lymphomatic biology. The T/NK-cell lymphoma entities were allocated into three categories: (i) cytotoxic memory T-cell and/or NK-cell lymphoma (n = 151) consisting of extranodal NK/T-cell tumors other than mycosis fungoides (MF); (ii) non-cytotoxic memory T-cell lymphoma (n = 142) consisting of nodal and cutaneous tumors such as angioimmunoblastic T-cell lymphoma, adult T-cell lymphoma/leukemia and MF; and (iii) anaplastic lymphoma kinase positive anaplastic large cell lymphoma (n = 110) that has unique features and might be regarded as cytotoxic 'naive' T-cell lymphoma. Overall, these three categories were significantly correlated with age of onset, anatomical sites, the level of expression of cytotoxic molecules and CD45RO, and association with Epstein-Barr virus. This concept might provide a new insight enabling further understanding of the interrelationships among WHO T/NK-cell disease entities.

Adolescent↗
PubMed2003

A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma.

BACKGROUND: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown. METHODS: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level. RESULTS: The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients. CONCLUSIONS: The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.

Adjuvants, Immunologic↗