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Dive into the research topics where Takahiko Nakane is active.

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Featured researches published by Takahiko Nakane.


Journal of Experimental & Clinical Cancer Research | 2009

Impact of relative dose intensity (RDI) in CHOP combined with rituximab (R-CHOP) on survival in diffuse large B-cell lymphoma

Yoshiki Terada; Hirohisa Nakamae; Ran Aimoto; Hiroshi Kanashima; Erina Sakamoto; Mizuki Aimoto; Eri Inoue; Hideo Koh; Takahiko Nakane; Yasunobu Takeoka; Masahiko Ohsawa; Ki-Ryang Koh; Takahisa Yamane; Yoshitaka Nakao; Kensuke Ohta; Atsuko Mugitani; Hirofumi Teshima; Masayuki Hino

BackgroundRecently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma.MethodsWe retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients.ResultsA multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6–1.0; P = 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI.ConclusionOur data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.


Leukemia & Lymphoma | 2012

Different immunoprofiles in patients with chronic myeloid leukemia treated with imatinib, nilotinib or dasatinib

Hirohisa Nakamae; Takako Katayama; Takahiko Nakane; Hideo Koh; Mika Nakamae; Asao Hirose; Kiyoyuki Hagihara; Yoshiki Terada; Yoshitaka Nakao; Masayuki Hino

Abstract Immunomodulation induced by dasatinib is reportedly related to better prognosis in chronic myeloid leukemia (CML). However, the underlying mechanism has not yet been fully elucidated. The immunoprofiles of 63 patients in the chronic phase of CML were evaluated during treatment with a tyrosine kinase inhibitor (imatinib, n = 36; nilotinib, n = 9; dasatinib, n = 18). The numbers of CD56 + CD57 + and CD3 + CD57 + cells increased significantly in the dasatinib group. The numbers of regulatory T-cells were comparable among the three groups. Dasatinib markedly enhanced natural killer (NK)-cell reactivity. Only one patient treated with dasatinib showed a slight cytomegalovirus (CMV) reactivation. In contrast, nilotinib suppressed NK-cell reactivity. Plasma levels of interleukin-8 (IL-8), interferon-γ inducible protein-10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all three groups, and plasma levels of granulocyte macrophage-colony stimulating factor (GM-CSF) were significantly elevated in the imatinib and dasatinib groups. Our results suggest the presence of a mechanism for dasatinib-associated immunomodulatory effects that is distinct from CMV reactivation and a decreased number of regulatory T-cells.


Haematologica | 2013

A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction

Yoshinori Shinohara; Naoto Takahashi; Kaichi Nishiwaki; Masayuki Hino; Makoto Kashimura; Hisashi Wakita; Yoshiaki Hatano; Akira Hirasawa; Yasuaki Nakagawa; Kuniaki Itoh; Masuoka H; Nobuyuki Aotsuka; Yasuhiro Matsuura; Sinobu Takahara; Koji Sano; Jun Kuroki; Tomoko Hata; Hirohisa Nakamae; Atsuko Mugitani; Takahiko Nakane; Yasushi Miyazaki; Takenori Niioka; Masatomo Miura; Kenichi Sawada

Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).


Bone Marrow Transplantation | 2008

Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation.

Takahiko Nakane; Hirohisa Nakamae; Kamoi H; Hideo Koh; Yasunobu Takeoka; Erina Sakamoto; Hiroshi Kanashima; Mika Nakamae; Kensuke Ohta; Yoshiki Terada; Ki-Ryang Koh; Takahisa Yamane; Masayuki Hino

Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS) cause high mortality and impaired survival after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Early recognition of patients at high risk of developing BOS/IPS may lead to improving the outcome of allo-HSCT. We retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than 90 days after allo-HSCT and compared values of these serum markers and other transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five patients developed BOS and two developed IPS at a median interval of 303 and 117 days (range, 100–452 and 95–153) from transplantation. As a result of univariate analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients were significantly lower than those in non-BOS/IPS patients (P=0.03). In multivariate analysis, the patients with lower pretransplant serum SP-D level had a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS.


Acta Haematologica | 2013

Dasatinib maintenance therapy after allogeneic hematopoietic stem cell transplantation for an isolated central nervous system blast crisis in chronic myelogenous leukemia.

Mitsutaka Nishimoto; Hirohisa Nakamae; Ki-Ryang Koh; Saori Kosaka; Kana Matsumoto; Kunihiko Morita; Hideo Koh; Takahiko Nakane; Masahiko Ohsawa; Masayuki Hino

A 22-year-old male with Ph-positive chronic myelogenous leukemia (CML) was started on treatment with imatinib. After 12 months of therapy, he achieved a complete cytogenetic response (CCyR). Although the CCyR persisted in his bone marrow, he developed an isolated CML blast crisis in his central nervous system (CNS) after 29 months of therapy. He underwent allogeneic hematopoietic stem cell transplantation (HSCT) following combination therapy with dasatinib, intrathecal chemotherapy and cranial irradiation. Subsequently, 168 days after allogeneic HSCT, he was started on dasatinib maintenance therapy to prevent a CNS relapse. Thirty-eight months after allogeneic HSCT, he has sustained a complete molecular response in both bone marrow and CNS. We believe dasatinib has the potential to prevent CNS relapse if used for maintenance therapy after allogeneic HSCT.


Transplant Infectious Disease | 2012

Fatal BK virus pneumonia following stem cell transplantation

Y. Akazawa; Yoshiki Terada; Takahisa Yamane; S. Tanaka; Mizuki Aimoto; Hideo Koh; Takahiko Nakane; Ki-Ryang Koh; Hirohisa Nakamae; Masahiko Ohsawa; Kenichi Wakasa; Masayuki Hino

We report the case of a 39‐year‐old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV‐associated late‐onset hemorrhagic cystitis (HC) with long‐term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late‐onset HC, but BKV‐associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients.


Journal of Experimental & Clinical Cancer Research | 2011

Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation

Hideo Koh; Hirohisa Nakamae; Kiyoyuki Hagihara; Takahiko Nakane; Masahiro Manabe; Mitsutaka Nishimoto; Yukari Umemoto; Mika Nakamae; Asao Hirose; Eri Inoue; Atsushi Inoue; Masahiro Yoshida; Masato Bingo; Hiroshi Okamura; Ran Aimoto; Mizuki Aimoto; Yoshiki Terada; Ki-Ryang Koh; Takahisa Yamane; Masahiko Ohsawa; Masayuki Hino

BackgroundThere has been insufficient examination of the factors affecting long-term survival of more than 5 years in patients with leukemia that is not in remission at transplantation.MethodWe retrospectively analyzed leukemia not in remission at allogeneic hematopoietic cell transplantation (allo-HCT) performed at our institution between January 1999 and July 2009. Forty-two patients with a median age of 39 years received intensified conditioning (n = 9), standard (n = 12) or reduced-intensity conditioning (n = 21) for allo-HCT. Fourteen patients received individual chemotherapy for cytoreduction during the three weeks prior to reduced-intensity conditioning. Diagnoses comprised acute leukemia (n = 29), chronic myeloid leukemia-accelerated phase (n = 2), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) (n = 10) and plasma cell leukemia (n = 1). In those with acute leukemia, cytogenetic abnormalities were intermediate (44%) or poor (56%). The median number of blast cells in bone marrow (BM) was 26.0% (range; 0.2-100) before the start of chemotherapy for allo-HCT. Six patients had leukemic involvement of the central nervous system. Stem cell sources were related BM (7%), related peripheral blood (31%), unrelated BM (48%) and unrelated cord blood (CB) (14%).ResultsEngraftment was achieved in 33 (79%) of 42 patients. Median time to engraftment was 17 days (range: 9-32). At five years, the cumulative probabilities of acute graft-versus-host disease (GVHD) and chronic GVHD were 63% and 37%, respectively. With a median follow-up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS) were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariable analyses of the influence of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%), MDS overt AML and CB as stem cell source were significantly associated with worse prognosis (p = .03, p = .01, p = .02 and p < .001, respectively). In addition, based on a landmark analysis at 6 months post-transplant, the five-year Kaplan-Meier estimates of OS in patients with and without prior history of chronic GVHD were 64% and 17% (p = .022), respectively.ConclusionGraft-versus-leukemia effects possibly mediated by chronic GVHD may have played a crucial role in long-term survival in, or cure of active leukemia.


International Journal of Hematology | 2009

Efficacy and safety of intravenous itraconazole as empirical antifungal therapy for persistent fever in neutropenic patients with hematological malignancies in Japan

Kensuke Ohta; Saori Kosaka; Yoshitaka Nakao; Takeo Kumura; Kiyomichi Hagihara; Erina Sakamoto; Shuichiro Okamoto; Asao Hirose; Yasutaka Aoyama; Ryousuke Yamamura; Yukari Umemoto; Yoshiki Terada; Yasunobu Takeoka; Takahiko Nakane; Hideo Koh; Masayuki Hino

Recently, empirical antifungal therapy with intravenous itraconazole (ITCZ) for neutropenic patients with antibiotics-resistant fever has been approved by Japanese Ministry of Health, Labour and Welfare on the bases of previous multicenter trials of foreign countries. In this study, we conducted a single-arm, multicenter, prospective study in order to evaluate the efficacy of empirical ITCZ injection on Japanese patients. Sixty-eight patients with hematological diseases who underwent anticancer chemotherapy or stem cell transplantation were enrolled. In this study, we found that the overall clinical response rate to ITCZ injection was 67.6% and success rate of achieving composite endpoints including survival, defervescence during neutropenia, no breakthrough fungal infections, and no premature discontinuation of drug was 50.0%. Mild adverse reactions were observed in 6 patients (8.8%). Further analysis revealed that possible/probable deep fungal infection according to the 2002 and 2008 criteria defined by EORTC/MSG were found in 19.1 and 7.5% of the patients, respectively. Interestingly, response rate to ITCZ injection of possible/probable cases according to the 2002 and 2008 criteria was 61.5% (8/13) and 100% (5/5), respectively. These results not only proved the good efficacy and safety of empirical ITCZ injection for Japanese patients, but also indicated a utility of the drug on future “presumptive” approach.


European Journal of Haematology | 2016

Analysis of elderly patients with diffuse large B-cell lymphoma: aggressive therapy is a reasonable approach for ‘unfit’ patients classified by comprehensive geriatric assessment

Masahiro Yoshida; Takafumi Nakao; Mirei Horiuchi; Hideya Ueda; Kiyoyuki Hagihara; Hiroshi Kanashima; Takeshi Inoue; Erina Sakamoto; Manabu Hirai; Hideo Koh; Takahiko Nakane; Masayuki Hino; Takahisa Yamane

The treatment strategy for diffuse large B‐cell lymphoma (DLBCL) in elderly patients is problematic. Although several researchers have reported the effectiveness of comprehensive geriatric assessment (CGA) and the futility of curative treatment in ‘unfit’ patients with DLBCL, these propositions are not firmly established.


Journal of Infection and Chemotherapy | 2015

Cefozopran, meropenem, or imipenem–cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients: A multicenter prospective randomized trial

Takahiko Nakane; Kazuo Tamura; Masayuki Hino; Toshiharu Tamaki; Isao Yoshida; Toshihiro Fukushima; Youichi Tatsumi; Yasuaki Nakagawa; Kazuo Hatanaka; Tsutomu Takahashi; Nobu Akiyama; Mitsune Tanimoto; Kazuma Ohyashiki; Akio Urabe; Toru Masaoka; Akihisa Kanamaru

We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem-cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem-cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem-cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem-cilastatin compared with cefepime were -5.9% (95% confidence interval (CI): -20.1-8.4), -0.7% (95% CI: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ≤ 100 × 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem-cilastatin compared with cefepime (clinical trial number: UMIN000000462).

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Hideo Koh

Osaka City University

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