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Nozomi Niitsu

Publications and source records attributed to Nozomi Niitsu.

At least 19 recordsLinked to original sources
PubMed2007

Prognostic impact of chromosomal alteration of 3q27 on nodal B-cell lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 329 consecutive patients.

Rearrangements involving the BCL6 gene are found in 30% of diffuse large B-cell lymphomas (DLBCLs). We evaluated the clinical characteristics and prognoses of patients with B-cell lymphoma carrying 3q27 translocations. Among the 59 patients having 3q27 translocation, 10.9% had follicular lymphoma (FL) and 23.1% had DLBCL. It is of interest that the prognostic significance was not found between FL and DLBCL with 3q27 translocations. Progression-free survival (PFS) rate was significantly higher in the FL patients with 3q27 translocation than in those with 18q21 translocation. PFS rate was significantly higher in the DLBCL patients with 3q27 translocation than in those with 18q21 translocation. These findings suggest that the presence of 3q27 translocation is a significant prognostic factor in DLBCL.

Adult↗
PubMed2007

Phase II study of the irinotecan (CPT-11), mitoxantrone and dexamethasone regimen in elderly patients with relapsed or refractory peripheral T-cell lymphoma.

We treated elderly patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) using a CMD (CPT-11, mitoxantrone [MIT], dexamethasone [DEX]) regimen and studied its safety and efficacy. The subjects were 70-79-year-old patients with relapsed or refractory PTCL. CPT-11 at 25 mg/m2 on days 1 and 2, MIT at 8 mg/m2 on day 3, and DEX at 40 mg/day on days 1-3 were administered once every 3 weeks, and this was performed for six cycles. Eleven (37%) of the 30 patients achieved complete remission and seven patients (23%) achieved partial remission. With a median follow-up period of 32 months, the 3-year survival rate was 28.2% and the 3-year progression-free survival rate was 17.5%. The main adverse drug reaction was hematological toxicity and there were no deaths related to the treatment. B-type natriuretic peptide and troponin T levels did not increase after the treatment and none of the patients showed electrocardiogram or echocardiogram abnormalities. Our results indicate that the CMD regimen is safe in elderly patients and no cardiotoxicities developed as a result of this regimen. In addition, it was effective in patients who had previously been treated with doxorubicin and good treatment results were obtained in elderly patients with relapsed PTCL.

Aged↗
PubMed2006

t(8;14)(q24;q32) in two patients with CD10-negative primary thyroid diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) with the 8q24 translocation is occasionally seen in the gastrointestinal tract, but has rarely been reported in the thyroid gland. We experienced two cases of primary thyroid DLBCL having t(8;14)(q24;q32). The immunophenotype and karyotype of Case 1 (66-year-old female) and Case 2 (70-year-old female) were: CD10-, CD20+, BCL-2+/add(13)(q34), t(8;14)(q24;q32) and CD10-, CD20-, CD79a+, BCL-2-/t(8;14)(q24;q32), respectively. Although long-term complete remission could be achieved in both of our patients by conventional chemotherapy with/without radiation therapy, accumulation of further such cases is necessary to develop a standard treatment protocol and also to elucidate the pathogenesis of t(8;14)(q24;q32)-positive primary thyroid DLBCL.

Aged↗
PubMed2006

Phase II study of the CPT-11, mitoxantrone and dexamethasone regimen in combination with rituximab in elderly patients with relapsed diffuse large B-cell lymphoma.

Standard treatment for elderly patients with relapsed or refractory DLBCL has not been established. CPT-11 has a broad spectrum of anticancer activities including a cytotoxic effect in a variety of malignant tumors. The results of combined treatment with CPT-11 and rituximab have not been reported. The R-CMD regimen was given to elderly patients with relapsed or refractory DLBCL. The safety and efficacy of this regimen were studied. In addition, the serum nm23-H1 level was determined to study whether or not it can serve as a prognostic factor. Thirty elderly patients with DLBCL were studied. The main non-hematological toxicities were infusion-related adverse events. Grade 3/4 hematological toxicity was seen in 19 patients. Following R-CMD treatment, the BNP and troponin T levels did not increase. The CR rate was 57%, PR rate was 17%, 2-year survival rate was 45.2%, and PFS rate was 37.2%. Patients with serum nm23-H1 levels of higher than 80 ng/mL before the treatment showed significantly poorer prognosis. The serum nm23-H1 level of the 30 subjects before the treatment was elevated at 39.4 +/- 41.3 ng/mL, but it significantly decreased only in the subset of patients who achieved CR. The R-CMD regimen was safe in elderly patients with DLBCL. No new signs of cardiotoxicity were observed with this regimen. It was also effective in patients with relapsed or refractory DLBCL who had previously used DXR.

Aged↗
PubMed2006

Multicenter phase II study of the CyclOBEAP (CHOP-like + etoposide and bleomycin) regimen for patients with poor-prognosis aggressive lymphoma.

Our aim was to study the efficacy of the addition of etoposide and bleomycin to a [cyclophosphamide (CPA), doxorubicin (DXR), vincristine (VCR), and prednisone (PDN)] CHOP-like regimen for the treatment of aggressive lymphoma. The CyclOBEAP regimen was administered over a total period of 12 weeks. Doxorubicin, 50 mg/m(2), was given every 2 weeks in combination with either cyclophosphamide, 1,000 mg/m(2), (weeks 1, 5, 9) or etoposide, 70 mg/m(2) qd x4 (weeks 3, 7, 11). During the alternate weeks, non-myelosuppressive vincristine, 1.4 mg/m(2) (maximum, 2.0 mg/body), was given either with bleomycin, 10 mg/m(2) (weeks 2, 6, 10), or alone (weeks 4,8,12). Prednisolone, 40 mg/m(2), was administered daily for 14 days during weeks 1-2, 5-6, and 9-10. There were 121 eligible patients and median age of 51 years. A complete response was achieved in 106 patients (88%) and a partial response in 11 patients. The 5-year overall survival (OS) rate was 72% and progression-free survival (PFS) rate was 62%. When the patients were divided according to the International Prognostic Index (IPI), the 5-year OS and PFS rates did not significantly differ among risk groups. When the patients with DLBCL were divided according to the IPI, the 5-year OS and PFS rates also did not significantly differ. World Health Organization (WHO) grade 4 neutropenia was observed in 91 patients and thrombocytopenia in 13 patients. No treatment-related deaths were observed. The addition of etoposide and bleomycin to CHOP therapy may enhance the effect of CHOP therapy for aggressive lymphoma. We will perform a prospective study of CyclOBEAP regimen combined with rituximab and test its safety and efficacy.

Adolescent↗
PubMed2006

Multicenter Phase II study of CyclOBEAP regimen for elderly patients with poor-prognosis aggressive lymphoma.

We treated elderly patients (65-69 years) who had aggressive lymphoma with the CyclOBEAP regimen, and we studied the safety and efficacy of this treatment. The CyclOBEAP regimen was administered over a total period of 12 weeks. Doxorubicin 40 mg/m(2) was given every 2 weeks in combination with either cyclophosphamide 800 mg/m(2) or etoposide 70 mg/m(2) qd x 3. During the alternate weeks, non-myelosuppressive vincristine 1.0 mg/m(2) was given either with bleomycin 10 mg/m(2) or alone. Prednisolone 40 mg/m(2) was administered daily for three 14-day periods during weeks 1-2, 5-6 and 9-10. There were 51 eligible patients. A complete response was achieved in 42 patients (82%). The 5-year overall survival (OS) rate was 60.6% and progression-free survival (PFS) rate was 51.8%. WHO grade 4 neutropenia was observed in 32 patients and thrombocytopenia in 8 patients. We showed that the CyclOBEAP regimen can be safely used in the treatment of aggressive lymphoma in elderly patients and it achieved a high rate of remission.

Aged↗
PubMed2006

Multicentre phase II study of the baseline BEACOPP regimen for patients with advanced-stage Hodgkin's lymphoma.

A German Hodgkin's lymphoma (HL) study group designed the BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) regimen. In the BEACOPP regimen, treatment intervals were shortened and the dose-intensity was increased compared with those in the ABVD regimen (doxorubicin, bleomycin, vinblastine and darcarbacine), resulting in a long-term disease-free survival rate of approximately 75-80%. In the present study, we evaluated the safety and efficacy of the BEACOPP regimen. Between April 2001 and February 2004, 20 patients with HL of stage IIB or higher who had received no previous treatment were enrolled. The patients were aged 17-69 years (median 22 years). The histologic types were mixed cellularity in four cases and nodular sclerosis in 16 cases. The stages were stage IIB in four cases, stage III in 12 cases, and stage IV in four cases. Nineteen (95%) of the 20 patients achieved complete remission. The 3-year survival rate was 100% and the 3-year progression-free survival rate was 89.7%. Adverse drug reactions were grade 4 neutropenia in 12 patients, grade 3-4 thrombocytopenia in seven patients, and grade 3 or higher non-hematologic toxicities in two patients (stomatitis in one patient and ALT/AST elevation in one patient). The BEACOPP regimen for advanced-stage HL showed an excellent complete remission rate and high efficacy even in stage III/IV patients. However, a long-term risk of the BEACOPP regimen is the development of secondary leukemia or myelodysplastic syndrome. Therefore, long-term follow-up of these patients, including monitoring for toxicities, is necessary.

Adolescent↗
PubMed2005

Phase I/II study of the rituximab-EPOCT regimen in combination with granulocyte colony-stimulating factor in patients with relapsed or refractory follicular lymphoma including evaluation of its cardiotoxicity using B-type natriuretic peptide and troponin T levels.

PURPOSE: Standard treatment for relapsed or refractory follicular lymphoma has not been established. Doxorubicin is often given during the initial treatment. The dosage or drugs chosen for salvage therapy are limited by doxorubicin-induced cardiomyopathy. EXPERIMENTAL DESIGN: The R-EPOCT (rituximab with etoposide, vincristine, pirarubicine, cyclophosphamide, and prednisone) regimen, in which less cardiotoxic pirarubicine is used instead of doxorubicin, with granulocyte colony-stimulating factor (G-CSF) was administered to 20 patients with relapsed or refractory follicular lymphoma. The safety (especially cardiotoxicity) and efficacy of this regimen were studied. As markers of cardiotoxicity, serum troponin T and plasma B-type natriuretic peptide (BNP) levels were measured. RESULTS: Adverse reactions occurred in 14 of the 20 patients and mainly consisted of grade 3/4 hematologic toxicity. In the evaluation of cardiotoxicity, the BNP level was slightly elevated before the treatment in two patients and the BNP level did not significantly increase after R-EPOCT treatment. The troponin T level was undetectable before and after the treatment in all patients. The response rate was 100%, with complete remission in 16 patients (80%). G-CSF administration increased both Fc gamma receptor type I expression on neutrophils and antibody-dependent cellular cytotoxicity activity. There were no significant differences in the levels of Fc gamma receptor type I expression nor antibody-dependent cellular cytotoxicity activity after three or five cycles of the treatment. CONCLUSION: We conclude that the combination of R-EPOCT and G-CSF is well tolerated. This regimen was not cardiotoxic. We are planning a randomized trial to compare the efficacy between R-EPOCT and a combination of R-EPOCT with G-CSF.

Adult↗
PubMed2005

Primary pulmonary plasmacytoma involving bilateral lungs and marked hypergammaglobulinemia: differentiation from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

A 71-year-old woman was referred to our hospital because of hyperproteinemia and serum M-protein (IgG-lambda type). Chest computed tomographic (CT) scan revealed a tumor in each lung and transbronchial lung biopsy was performed. Histopathological examination showed monotonous medullary proliferation of morphologically mature plasma cells. These cells were cIgG+, cIg-lambda+, CD 20+, CD 79 a+, CD 138+, cIg-kappa-, and CD3-. Since there were very few non-neoplastic plasma cells and small lymphocytes in addition to the absence of reactive lymph follicles and fibrosis, the patient was diagnosed as having plasmacytoma. There was no proliferation of plasma cells in the bone marrow. Thus, the lesion was finally characterized as primary pulmonary plasmacytoma. Treatment with melphalan/prednisolone resulted in considerable decrease in the serum IgG level and regression of the pulmonary tumors. The effectiveness of the chemotherapy could confirm our diagnosis, although MALT-type lymphoma with plasmacytic differentiation cannot be completely ruled out.

Aged↗
PubMed2004

Phase I study of Rituximab-CHOP regimen in combination with granulocyte colony-stimulating factor in patients with follicular lymphoma.

PURPOSE: Rituximab is an anti-CD20 monoclonal antibody, and it is used to treat B-cell lymphomas. Antibody-dependent cellular cytotoxicity (ADCC) is considered one of the mechanisms through which rituximab exerts its effects. Granulocyte colony-stimulating factor (G-CSF) enhances the cytotoxicity of neutrophils through ADCC, and it can be speculated that a combination of rituximab and G-CSF may augment the treatment efficacy of rituximab. EXPERIMENTAL DESIGN: We administered rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) treatment with G-CSF to 15 patients with follicular lymphoma, and we investigated the safety and efficacy of this regimen. We investigated ADCC activity in neutrophils and the expression of cell surface antigens including Fcgamma receptor type I [FcgammaRI (CD64)] on neutrophils to determine the optimal dose of G-CSF. RESULTS: Adverse reactions occurred in 14 of 15 patients and consisted mainly of grade 3/4 hematological toxicity. The response rate was 100%, with complete remission in 12 patients (80%) and partial remission in 3 patients (20%). At 14 months, the median length of the observation period, 2 of 12 patients had relapsed. G-CSF administration increased both FcgammaRI expression and ADCC activity. There were no significant differences in the levels of FcgammaRI expression or ADCC activity between the 2 microg/kg G-CSF and 5 microg/kg G-CSF groups, indicating that the optimal dose of G-CSF was 2 microg/kg. CONCLUSIONS: We conclude that the combination of rituximab-CHOP and G-CSF is well tolerated. We plan to carry out a randomized trial to compare efficacy between rituximab-CHOP treatment and treatment with a combination of rituximab-CHOP and G-CSF.

Adult↗
PubMed2004

Clinical significance of intracytoplasmic nm23-H1 expression in diffuse large B-cell lymphoma.

PURPOSE: Recently, we established an ELISA technique for measuring nm23-H1 protein in serum and found that the serum nm23-H1 level is a potential prognostic factor for patients with non-Hodgkin's lymphoma. EXPERIMENTAL DESIGN: We used immunohistochemistry to examine the expression of nm23-H1 by the lymphoma cells in patients with diffuse large B-cell lymphoma (DLBCL). RESULTS: By analyzing a consecutive series of 172 untreated DLBCL patients, we found that 100 (58.1%) were strongly positive. The cytoplasmic nm23 expression in lymphoma cells correlated significantly with the serum nm23-H1 level. There was a significant correlation between patients with cytoplasmic nm23-positive lymphoma and those with performance status 2-4, stage III/IV, bulky mass, B symptoms, elevated serum level of soluble interleukin 2 receptor, and elevated serum level of C-reactive protein. Overall and progression-free survival rates were significantly lower in patients with nm23-H1-positive lymphomas than in those with nm23-H1-negative lymphomas. Similar difference was seen between patients with high and low serum levels of nm23-H1. Thus, the correlation between presence or absence of cytoplasmic nm23-H1 expression and serum nm23-H1 levels suggests that serum nm23-H1 is produced directly by lymphoma cells. CONCLUSION: We suggest that nm23-H1 expression is a prognostic factor for DLBCL, and that it is as important as serum nm23-H1, both of which are useful for planning a treatment strategy.

Adolescent↗
PubMed2004

Granulocytic differentiation of leukemic cells with t(9;11)(p22;q23) induced by all-trans-retinoic acid.

Acute leukemia patients with MLL (mixed linage leukemia) rearrangements tend to respond poorly to conventional therapies. We examined differentiation of human myeloid leukemia cells displaying the MLL-AF9 gene, using several differentiation agents. When MOLM-14 cells were treated with all-trans retinoic acid (ATRA) or 1beta,25-dihydroxyvitamin D3, significant induced differentiation was observed. Trichostatin A (TSA), an inhibitor of histone deacetylase, demonstrated enhance effects with ATRA in regard to growth inhibition and differentiation induction in MOLM-14 cells. Pretreatment with TSA before exposure to ATRA displayed increased effect. Based on these findings, combined treatment with ATRA and TSA may be clinically useful in therapy for acute leukemia displaying MLL-AF9 fusion gene.

Acute Disease↗
PubMed2004

Development of hepatosplenic gammadelta T-cell lymphoma with pancytopenia during early pregnancy: a case report and review of the literature.

Lymphomas rarely develop during pregnancy, but hepatosplenic gammadelta T-cell lymphoma (HSgammadeltaTCL) is extremely rare. We encountered a case of T-cell intracellular antigen-1 (TIA-1) positive and granzyme B-positive HSgammadeltaTCL that developed early during the course of pregnancy. The patient was a 31-yr-old female who was referred to our hospital because of pancytopenia and splenomegaly at the time of the14th week of her gestation. Her pancytopenia and hepatosplenomegaly worsened and she became fibril at the 27th week of gestation and Cesarean section was performed at the 29th week. Histopathological examination of the spleen, which was resected 28 d after delivery for a diagnostic purpose, revealed medium to large-sized nodules composed of dense proliferation of lymphoid cells having round to oval-shaped nuclei and abundant weakly eosinophilic cytoplasm. They were CD3epsilon+, mCD3+, CD4-, CD8-, CD56+, CD79a-, T-cell receptor (TCR)-gammadelta protein+, TIA-1+, and granzyme B+ by either immunohistochemistry or flow cytometry. Clonal rearrangement of TCR-gamma genes without such rearrangement of TCR-delta and TCR-beta genes was confirmed by Southern blot hybridization. Thus, the patient was diagnosed as having HSgammadeltaTCL, and combination chemotherapy was initiated. She is currently in partial remission. To our knowledge, this is the first case report of HSgammadeltaTCL that developed during pregnancy. Pathogenesis of pregnancy-associated lymphoma is not known, but it is possible that maternal immunity during pregnancy or a hormonal imbalance, such as a change in the progesterone level, induces the development of lymphoma. Pregnancy-associated lymphoma is resistant to standard chemotherapy and is associated with poor prognosis. Therefore, it is important to accumulate clinicopathologic data of such cases for the development of a treatment modality.

Adult↗
PubMed2003

Expression of nm23-H1 is associated with poor prognosis in peripheral T-cell lymphoma.

We have reported previously that the serum nm23-H1 level is a prognostic factor for non-Hodgkin's lymphoma. In this study, we examined nm23-H1 expression in T- and natural killer (NK)-cell lymphoma in order to evaluate whether lymphoma cells produce the protein. The clinical significance of the cytotoxic molecules, T-cell intracellular antigen-1 (TIA-1) and granzyme B and nm23-H1 expression were also examined. Expression of nm23-H1, TIA-1, or granzyme B was examined by immunohistochemistry in 137 previously untreated lymphoma patients. The relationship between the results and clinical outcome was examined in 81 patients with angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, or peripheral T-cell lymphoma, unspecified. The neoplastic cells of some lymphomas produced nm23-H1 and the expression rates of nm-23-H1, TIA-1 and granzyme B were 36.5%, 78.8% and 32.8% respectively. The nm23-H1-positive or TIA-1-positive groups had significantly shorter overall and disease-free survivals. Multivariate analysis confirmed nm23-H1 expression to be an independent prognostic factor. The nm23-H1 protein can be an important prognostic factor in the lymphomas studied here. New treatments that target nm23 overexpression could be developed as a result of nm23-HI production by lymphoma cells.

Adult↗