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Nishi-Tokyo-shi, Japan

Yoshida C.,National Hospital Organization Mito Medical Center | Fletcher L.,University of Adelaide | Ohashi K.,Tokyo Metropolitan Cancer and Infectious Diseases Center | Wakita H.,Red Cross | And 10 more authors.
International Journal of Clinical Oncology | Year: 2012

Background: Real-time quantitative polymerase chain reaction (RQ-PCR) has been widely used for molecular monitoring for patients with chronic myeloid leukemia (CML). Currently, RQ-PCR is not based on the concept of international scale (IS) in Japan; mainly because none of the domestic laboratories have obtained their own conversion factor (CF) which makes it possible to convert locally scaled BCR-ABL (BCR-ABL L) value to the IS (BCR-ABL IS). To join the global trend of molecular assessment of BCR-ABL in CML patients, we have tried to obtain a CF in Japan. Methods: Samples from 55 patients were exchanged between the Japanese laboratory and the reference laboratory in Adelaide, and BCR-ABL and internal control gene transcripts of the samples were measured using RQ-PCR. The patient bias conversion method was used to determine the CF for the IS using the Bland and Altman method. Results: The local CF in the Japanese laboratory was determined to be 0.87. Based on this CF, 0.1% BCR-ABL IS, defined as major molecular response, becomes equivalent to 731 copy/μg RNA BCR-ABL L. Conclusion: This study is the first to introduce a laboratory-specific CF for harmonizing RQ-PCR methodology for detecting BCR-ABL transcripts to Japan, which may open new windows for molecular assessment of CML patients in Japan. © 2011 Japan Society of Clinical Oncology. Source


Iriyama N.,Nihon University | Fujisawa S.,Yokohama City University | Yoshida C.,National Hospital Organization Mito Medical Center | Wakita H.,Red Cross | And 14 more authors.
American Journal of Hematology | Year: 2015

To investigate the factors that affect molecular responses on dasatinib treatment in patients with chronic-phase chronic myeloid leukemia (CML-CP), we performed a clinical trial named the "D-First study." Fifty-two patients with newly diagnosed CML-CP were enrolled in this study and received 100 mg dasatinib once daily. A deep molecular response (DMR) was defined as <50 copies/μg RNA of BCR-ABL1 transcript value corrected by GAPDH, which ensures <0.01% of BCR-ABL1 transcript value according to International Scale (BCR-ABL1IS). The halving time for BCR-ABL1 transcripts was calculated using transcript levels before dasatinib treatment, transcript levels after 3 months of treatment, and the treatment time between these two points. In terms of molecular response, 38 of 51 (75%) patients reached major molecular response (MMR) by 12 months, and the rate of DMR by 18 months was 59% (30/51). While both BCR-ABL1 transcript levels before treatment and a shorter halving time of BCR-ABL1 transcripts (≤14 days) were significant factors affecting achievement of MMR by 12 months, the Sokal score at diagnosis was not associated with MMR. Importantly, the halving time was the only factor that predicted achievement of DMR by 18 months. We showed that patients with CML-CP treated with dasatinib can be stratified according to the early treatment response as determined by the halving time of BCR-ABL1 transcripts. These data emphasize the significance of the early response from dasatinib treatment in achieving a DMR. © 2014 Wiley Periodicals, Inc. Source


Kumagai T.,Ohme Municipal General Hospital | Matsuki E.,Keio University | Inokuchi K.,Nippon Medical School | Ohashi K.,Tokyo Metropolitan Cancer and Infectious Diseases Center | And 14 more authors.
International Journal of Hematology | Year: 2014

Lymphocytosis in response to dasatinib for chronic myelogenous leukemia (CML) may be associated with favorable response. However, it occurs at varying times and in a limited subset of patients. To identify early clinical markers for favorable responses applicable to all patients with or without lymphocytosis, we prospectively analyzed lymphocyte profiles of 50 Japanese CML patients treated with dasatinib after intolerance/resistance to imatinib. Although absolute lymphocyte counts did not differ significantly until 3 months between patients with complete molecular response (CMR) at 12 months and those without it, relative increases in lymphocyte compared with baselines differed significantly from 1 month. Patients with relative lymphocyte counts >150% at 1 month or >200% at 3 months had higher CMR rates at 12 months than others (57.9 vs. 23.3%, P = 0.015, and 76.5 vs. 16.1%, P < 0.0001, respectively). A relative increase in lymphocyte subset of CD57+CD14-, CD8+T, or NK cells >200% at 1 month was also significantly associated with a higher CMR rate. There were significant negative correlations between relative lymphocyte increases and BCR/ABL transcript levels. CD57 +CD14- cells were a highly specific focus of proliferation. Relative increases in lymphocyte count and its subsets from 1 month are reliable early markers of favorable responses to dasatinib. © The Japanese Society of Hematology 2013. Source


Ohyagi M.,Ohme Municipal General Hospital | Tao O.,Ohme Municipal General Hospital | Mizutani T.,Tokyo Metropolitan Tama Medical Center | Takahashi M.,Ohme Municipal General Hospital | Mizusawa H.,Tokyo Medical and Dental University
Internal Medicine | Year: 2013

Bilateral internal carotid artery dissection (ICAD) is a rare but important cause of stroke in young adults. Anticoagulant and/or antiplatelet agents are usually recommended for stroke prevention;however, such treatments remain highly controversial, and there are inadequate data to compare the efficacy of anticoagulation and antiplatelet therapy. We herein report the case of 30-year-old man presenting with progressive bilateral ICAD during antiplatelet treatment. This report suggests the possibility that intramural hematomas are enlarged by antiplatelet and anticoagulant agents and draws attention to the medications associated with ICAD. © 2013 The Japanese Society of Internal Medicine. Source


Iriyama N.,Nihon University | Fujisawa S.,Yokohama City University | Yoshida C.,Mito Medical Center | Wakita H.,Red Cross | And 14 more authors.
American Journal of Hematology | Year: 2015

Dasatinib is one of the key treatment options for chronic myeloid leukemia (CML) patients. Increase in lymphocyte counts has been known to be predictive of a good treatment response under dasatinib treatment as a second line therapy. However, clinical significance of lymphocyte dynamics in the upfront setting has yet to be clarified. To investigate the significance of lymphocyte dynamics in newly diagnosed chronic phase (CP)-CML, patient data of D-First study (ClinicalTrials.gov NCT01464411) were analyzed. Fifty-two CML-CP patients enrolled to this study were treated with dasatinib (100 mg day-1) and all were followed-up for 18 months. The incidence of lymphocyosis was observed in 14 (27%), but it was not associated with deep molecular response achievement. However, natural killer (NK) cell or cytotoxic T lymphocyte (CTL) counts at 1 month were significantly higher in patients with deep molecular response (DMR) by 18 months compared to those without DMR. When the patients were divided into two groups according to those calculated thresholds by receiver operating characteristic curve (407/μL for NK cells and 347/μL for CTLs), the cumulative DMR rates by 18 months were significantly better in higher value group compared to lower value group. In contrast, regulatory T cell counts were significantly lower at 12 and 15 months in patients achieved DMR. These results suggest the presence of dual effects of dasatinib on immune system through the cytotoxic lymphocytes activation and Treg deregulation in different periods in newly diagnosed CML-CP. © 2015 Wiley Periodicals, Inc. Source

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