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Akira Shirahata,
Tadashi Kamiya,
Junki Takamatsu,
Tetsuhito Kojima,
Katsuyuki Fukutake,
Morio Arai,
Hideji Hanabusa,
Hisamichi Tagami,
Akira Yoshioka,
Midori Shima,
Hiroyuki Naka,
Shigeru Fujita,
Yoko Minamoto, Junji Kamizono,
Hidehiko Saito
[show abstract]
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ABSTRACT: A multicenter and open-labeled clinical trial of human recombinant factor VIIa (rFVIIa) was conducted in Japanese patients with severe hemophilia A or B with inhibitors. The trial consisted of 2 parts. In study
1, the pharmacokinetics, pharmacodynamics, and safety of a single dose of 120 μg/kg ofrFVIIa were investigated in 8 patients. In the subsequent study 2, the hemostatic effect and safety ofrFVIIa were evaluated during a 24-week period in 10 patients. In study 1, the mean maximum FVII-coagulant activity (FVII:C)
was found to occur after 10 minutes; activity then decreased rapidly and returned to the baseline within 24 hours after a
single intravenous infusion of rFVIIa. The mean half-life of FVII:C was 3.5 hours. The activated partial thromboplastin time
and prothrombin time in the patients were immediately shortened but returned to the baseline within 24 hours after dosing.
In study 2, 86 μg/kg to 120 μg/kg ofrFVIIa (mean, 97 μg/kg) was administered 1 to 85 times to 10 patients. A total of 58.0% (91/157) of bleeding episodes were
treated excellently or effectively, with 5 (3.2%) ineffective episodes. There was no apparent trend in the relationship of
the hemostatic effect with bleeding sites, mean dose, or number of injections. The efficacy rate, however, was significantly
higher (90.0%) in bleeding episodes treated within 3 hours than in those treated at longer intervals (31.0%). No treatment-related
adverse events were observed, and there was no evidence of antibody formation to rFVIIa. In conclusion,rFVIIa is an effective and well-tolerated option for treatment of bleeding episodes in hemophilia patients with inhibitors.
International Journal of Hematology 04/2012; 73(4):517-525. · 1.27 Impact Factor
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Akira Morimoto,
Yoko Shioda,
Toshihiko Imamura,
Hirokazu Kanegane,
Takashi Sato,
Kazuko Kudo,
Shinichiro Nakagawa,
Hisaya Nakadate,
Hisamichi Tauchi,
Asahito Hama,
Masahiro Yasui,
Yoshihisa Nagatoshi,
Akitoshi Kinoshita,
Ryosuke Miyaji,
Tadashi Anan,
Miharu Yabe, Junji Kamizono
[show abstract]
[hide abstract]
ABSTRACT: Several studies have suggested that Langerhans cell histiocytosis (LCH) is responsive to treatment with bisphosphonates (BPs). However the efficacy and safety of BPs therapy for childhood LCH is unknown.
Data on children with LCH who had received BPs therapy were collected retrospectively from hospitals participating in the Japanese Pediatric Leukemia/Lymphoma Study Group.
Twenty-one children with histologically proven LCH were identified. Of these, the case histories of 16 children who had been treated with pamidronate (PAM) for disease reactivation were analyzed in detail. The median post-PAM therapy follow-up period was 2.8 years (range: 0.9-9.3 years). The median age at commencement of PAM therapy was 9.4 years (range: 2.3-15.0 years). All children had one or more bone lesions but none had risk organ (RO) involvement. In the majority of the children, six courses of PAM were administered at a dose of 1.0 mg/kg/course at 4-week intervals. In 12 of the 16 children, all active lesions including lesions of the skin (n = 3) and soft tissues (n = 3) resolved. Of these children, eight children had no active disease for a median of 3.3 years post-PAM therapy (range: 1.8-9.3 years). Progression-free survival (PFS) was 56.3 ± 12.4% at 3 years. PFS was significantly higher in children with a first reactivation compared with children experiencing a second or subsequent reactivation.
PAM may be an effective treatment for reactivated LCH with bone lesions. A prospective trial of the efficacy of PAM in recurrent pediatric LCH is warranted.
Pediatric Blood & Cancer 01/2011; 56(1):110-5. · 1.89 Impact Factor
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[show abstract]
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ABSTRACT: The aim of this study was to assess the outcome of treatment with 2-chlorodeoxyadenosine (2-CdA) in pediatric patients with Langerhans cell histiocytosis (LCH) in Japan. We retrospectively identified 17 pediatric LCH patients treated with 2-CdA. All patients were refractory or reactivated cases who had been initially treated according to the JLSG-02 protocol of the Japan LCH study group. At initiation of 2-CdA therapy, 4 patients had primary refractory multisystem (MS) disease with risk organ (RO) involvement (MS+), 9 patients had reactivated MS disease [5 MS+ and 4 without RO involvement (MS-)], and the remaining 4 patients had refractory/reactivated multifocal bone disease (MFB). Treatment with 2-CdA (4-9 mg/m(2)/day) was administered on 2-5 consecutive days and repeated every 3-4 weeks for a period that ranged from 2 to 12 months. Four primary refractory patients were treated with 2-CdA combined with high dose of cytarabine. In MS+ patients, response to treatment was observed in 5 of the 9 patients. In MS-/MFB patients, 5 of the 8 patients showed response to treatment. In the patients who were primary refractory or had reactivation during initial chemotherapy, 4 of 10 patients showed good response. On the other hand, in the patients having reactivation while off therapy, 6 of 7 patients showed good response. These findings suggest that 2-CdA is effective for reactivated LCH while off therapy.
International journal of hematology 04/2010; 91(4):646-51. · 1.17 Impact Factor
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Hiromichi Taneichi,
Hirokazu Kanegane,
Takeshi Futatani,
Keisuke Otsubo,
Keiko Nomura,
Yuya Sato,
Asahito Hama,
Seiji Kojima,
Urara Kohdera,
Takahide Nakano, [......],
Yoko Inoh, Junji Kamizono,
Naoto Adachi,
Yuko Osugi,
Haruo Mizuno,
Noriko Hotta,
Hiroshi Yoneyama,
Eiji Nakashima,
Shiro Ikegawa,
Toshio Miyawaki
[show abstract]
[hide abstract]
ABSTRACT: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities. SBDS was identified as a causative gene for SDS in 2003, and genetic analyses of SDS have been performed. We performed genetic analysis of 13 Japanese patients with presumed SDS and found that 10 of them had SBDS mutations. Most patients had recurrent mutations (181-184TA-->CT and 258+2T-->C); however, 2 patients had unique mutations (259-1G-->A and 428C-->G). Although genetic analysis is useful for definitive diagnosis and for genetic counseling of SDS patients and families, SDS appears to be a genetically heterogeneous disorder. In addition, presumed SDS patients without SBDS mutations may be included in other disorders.
International Journal of Hematology 07/2006; 84(1):60-2. · 1.27 Impact Factor
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Pediatrics International 09/2004; 46(4):480-3. · 0.63 Impact Factor
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Journal of Bone and Mineral Research 12/2002; 17(11):1926-8. · 6.37 Impact Factor
