研究者業績

工藤 寿子

Kazuko Kudo

基本情報

所属
藤田医科大学 医学部 医学科 小児科学
学位
医学博士

J-GLOBAL ID
200901067857002933
researchmap会員ID
5000075863

論文

 120
  • Akira Morimoto, Yoko Shioda, Kazuko Kudo, Hirokazu Kanegane, Toshihiko Imamura, Katsuyoshi Koh, Yoshiyuki Kosaka, Yuki Yuza, Atsuko Nakazawa, Akiko M Saito, Tomoyuki Watanabe, Yozo Nakazawa
    International journal of hematology 118(1) 107-118 2023年7月  
    Chemotherapy with cytarabine, vincristine (VCR), and prednisolone has achieved low mortality rates in pediatric patients with Langerhans cell histiocytosis (LCH). However, relapse rates remain high, making event-free survival (EFS) rates unsatisfactory. A nationwide clinical trial, LCH-12, tested a modified protocol in which the early maintenance phase was intensified with increasing dosages of VCR. Patients newly diagnosed with multifocal bone (MFB) or multisystem (MS) LCH and aged < 20 years at diagnosis were enrolled between June 2012 and November 2017. Of the 150 eligible patients, 43 with MFB were treated for 30 weeks and 107 with MS LCH were treated for 54 weeks. One patient with MS LCH died of sepsis during the induction phase. The 3-year EFS rates among patients with MFB LCH, risk organ (RO)-negative MS LCH, and RO-positive MS LCH were 66.7% (95% confidential interval [CI], 56.5-77.0%), 66.1% (95% CI 52.9-76.4%), and 51.1% (95% CI 35.8-64.5%), respectively, similar to previously observed rates. EFS rates were significantly lower in patients with disease activity scores > 6 than in those with scores ≤ 6. The strategy that included more intense treatment with VCR was not effective. Other strategies are required to improve outcomes in patients with pediatric LCH.
  • Makito Tanaka, Hiroki Miura, Soichiro Ishimaru, Gen Furukawa, Yoshiki Kawamura, Kei Kozawa, Seiji Yamada, Fumitaka Ito, Kazuko Kudo, Tetsushi Yoshikawa
    Pediatric reports 15(2) 333-340 2023年5月26日  
    Central nervous system (CNS) involvement in anaplastic large cell lymphoma (ALCL) at diagnosis is rare and leads to poor prognosis with the use of the standard ALCL99 protocol alone. CNS-directed intensive chemotherapy, such as an increased dose of intravenous MTX, increased dose of dexamethasone, intensified intrathecal therapy, and high-dose cytarabine, followed by cranial irradiation, has been shown to improve survival in this population. In this paper, the authors describe a 14-year-old male with an intracranial ALCL mass at onset who received CNS-directed chemotherapy followed by 23.4 Gy of whole-brain irradiation. After the first systemic relapse, the CNS-penetrating ALK inhibitor, alectinib, was applied; it has successfully maintained remission for 18 months without any adverse events. CNS-penetrating ALK inhibitor therapy might prevent CNS relapse in pediatric ALK-positive ALCL. Next-generation ALK inhibitors could be introduced as a promising treatment option, even for primary ALCL with CNS involvement, which could lead to the omission of cranial irradiation and avoid radiation-induced sequalae. Further evidence of CNS-penetrating ALK inhibitor combined therapy for primary ALK-positive ALCL is warranted to reduce radiation-induced sequalae in future treatments.
  • Mami Akamatsu, Yoshiki Kawamura, Hiroki Miura, Erina Sugimoto, Kaoru Okamoto, Yoichi Nakajima, Kei Kozawa, Gen Furukawa, Makito Tanaka, Kazuko Kudo, Tetsushi Yoshikawa
    Pediatric dermatology 40(3) 582-583 2023年  
    Eczema herpeticum (EH) is a disseminated cutaneous infection with herpes simplex virus (HSV) that develops in patients with atopic dermatitis. The kinetics and clinical significance of HSV viremia in EH are poorly understood. Herein, we report HSV DNAemia in a child with EH 12 months after the completion of chemotherapy for Hodgkin lymphoma.
  • Akira Morimoto, Yoko Shioda, Kenichi Sakamoto, Ko Kudo, Toshihiko Imamura, Kazuko Kudo
    [Rinsho ketsueki] The Japanese journal of clinical hematology 63(5) 373-382 2022年  
    Langerhans cell histiocytosis (LCH) is characterized by immature dendritic cell proliferation, which is currently classified as an inflammatory myeloid neoplasm. Clinical features and outcomes vary from spontaneously regressing isolated bone disease to fatal liver, spleen, or hematopoietic system (risk organ) involvement-positive multisystem disease. LCH cells have the only mutation in the mitogen-activated protein kinase (MAPK) signaling pathway gene, represented by the BRAF V600E mutation, which is the driver mutation. The type of disease depends on the stage of hematopoietic cell differentiation at which the mutation occurs. LCH cells acquire anti-apoptosis and senescence-associated secretory phenotype by oncogene-induced senescence, with migration failure to lymph nodes. These cause LCH cell accumulation and various inflammatory cell recruitment in the lesion, resulting in severe inflammation. Tissue damage in LCH is due to this inflammation, not the LCH cell proliferation. Patients with a risk of organ involvement without the initial treatment response may be rescued by allogeneic hematopoietic stem cell transplantation after reducing the disease activity with MAPK inhibitors. Intravenous zoledronic acid and intrathecal cytarabine injections have been introduced into the ongoing clinical trial in Japan to reduce bone recurrence and prevent neurodegeneration as sequelae.
  • 工藤 耕, 土岐 力, 金崎 里香, 小林 明恵, 佐藤 知彦, 神尾 卓哉, 佐々木 伸也, 今村 勝, 今井 千速, 安藤 久美子, 角田 治美, 土居 岳彦, 川口 浩史, 入江 正寛, 笹原 洋二, 田村 彰広, 長谷川 大一郎, 板倉 陽介, 渡邉 健一郎, 深野 玲司, 坂本 謙一, 塩田 曜子, 加藤 元博, 工藤 寿子, 金兼 弘和, 伊藤 悦朗, 照井 君典
    日本血液学会学術集会 83回 OS2-2 2021年9月  

MISC

 84
  • 前村遼, 村松秀城, 吉田太郎, 今屋雅之, 山森彩子, 若松学, 三輪田俊介, 成田幸太郎, 谷口理恵子, 市川大輔, 濱田太立, 西川英里, 川島希, 成田敦, 奥野友介, 西尾信博, 小島勢二, 三浦浩樹, 田中真己人, 工藤寿子, 吉川哲史, 山田勢至, 伊藤雅文, 高橋義行
    日本造血細胞移植学会総会プログラム・抄録集 43rd 2021年  
  • Akira Morimoto, Kazuko Kudo
    Expert Opinion on Orphan Drugs 8(9) 317-328 2020年9月1日  
    Introduction: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by accumulation of bone marrow-derived immature dendritic cells harboring oncogenic mutations in mitogen-activated protein kinase (MAPK) pathway genes, such as BRAF V600E, and various reactive inflammatory cells. Infants with chemo-resistant multisystem disease with risk organ involvement [MS-RO(+)] have poor prognosis. Further, relapsed infants have a significant risk of developing disastrous neuro-degenerative central nervous system disease. Areas covered: This review covers published papers on hematopoietic stem cell transplantation (HSCT) for LCH selected through a literature search on PubMed between years 1985 and 2019. Expert opinion: Infants with refractory MS-RO(+) disease or with frequent treatment-resistant relapses can benefit from allogeneic HSCT (allo-HSCT). Selection of an HLA-matched sibling or unrelated cord blood (UCB) stem cell source and use of reduced intensity conditioning (RIC) preparative regimens, based on the combination fludarabine with melphalan, are preferable. Most deaths after HSCT occur within 3 months, due to transplantation-related complications. LCH disease activity usually regresses over 3 months after allo-HSCT in survivors. The disease activity at HSCT is the most important prognostic factor. Prior to HSCT, the disease activity should be reduced by treatment.
  • Atsuro Saito, Yoshiyuki Kosaka, Daiichiro Hasegawa, Masataka Ishimura, Nobuyuki Hyakuna, Kazuko Kudo, Chiai Nagae, Hirohide Kawasaki, Akira Ishiguro, Midori Shima, Masashi Taki, Shouichi Ohga
    PEDIATRIC BLOOD & CANCER 65 S62-S62 2018年11月  
  • Kazuko Kudo, Miho Maeda, Nobuhiro Suzuki, Hirokazu Kanegane, Shouichi Ohga, Eiichi Ishii, Yoko Shioda, Toshihiko Imamura, Shinsaku Imashuku, Yukiko Tsunematsu, Mikiya Endo, Akira Shimada, Yuuki Koga, Yoshiko Hashii, Jiro Inagaki, Masami Inoue, Ken Tabuchi, Akira Morimoto
    BLOOD 132 2018年11月  
    0
  • Saito Atsuro, Kosaka Yoshiyuki, Hasegawa Daiichiro, Ishimura Masataka, Hyakuna Nobuyuki, Kudo Kazuko, Nagae Chiai, Kawasaki Hirohide, Ishiguro Akira, Shima Midori, Taki Masashi, Ohga Shouichi
    日本小児血液・がん学会雑誌 55(4) 244-244 2018年10月  
  • Makito Tanaka, Hiroki Miura, Fumihiko Hattori, Yui Nariai, Tetsushi Yoshikawa, Kazuko Kudo
    PEDIATRIC BLOOD & CANCER 64 S114-S114 2017年11月  
  • Akira Morimoto, Yoko Shioda, Toshihiko Imamura, Kazuko Kudo, Ichiro Murakami, Shinsaku Imashuku
    PEDIATRIC BLOOD & CANCER 64 S8-S8 2017年11月  
  • Hiroki Miura, Kazuko Kudo, Makito Tanaka, Yoshiyuki Takahashi, Seji Kojima, Koji Kato, Nao Yoshida, Hirotoshi Sakaguchi, Tetsushi Yoshikawa
    PEDIATRIC BLOOD & CANCER 64 S76-S76 2017年11月  
  • Akira Morimoto, Yukiko Oh, Sachie Nakamura, Yoko Shioda, Tomomi Hayase, Toshihiko Imamura, Kazuko Kudo, Shinsaku Imashuku
    CYTOKINE 97 73-79 2017年9月  
    Objective: Langerhans cell histiocytosis (LCH) is characterized by immature dendritic cell proliferation, infiltration of LCH lesions by various inflammatory cells, and a lesional cytokine storm. It is classified into three groups on the basis of disease extent, namely, multisystem with risk-organ involvement (MS +), multisystem without risk-organ involvement (MS -), and single-system (SS) disease. We comprehensively analyzed whether serum levels of cytokines/chemokines reflect the disease extent. Methods: Serum samples from 52 children with LCH (eight, 25, and 19 with MS +, MS -, and SS, respectively) and 34 control children were analyzed quantitatively for 48 humoral factors. DNA samples extracted from biopsied LCH lesions from 12 patients were tested for BRAF V600E status. Results: The LCH patients had significantly higher serum levels of IL-1Ra, IL-3, IL-6, IL-8, IL-9, IL-10, IL12, IL-13, IL-15, IL-17, IL-18, TNF-alpha, G-CSF, M-CSF, MIF, HGF, VEGF, CCL2, CCL3, CCL7, CXCL1, and CXCL9 than the controls by univariate analysis. Of these IL-9, IL-15 and MIF were significant by multivariate analysis; but not differed between MS and SS diseases. MS disease associated with significantly higher IL-2R, IL-3, IL-8, IL-18, M-CSF, HGF, CCL2, CXCL1, and CXCL9 levels than SS disease by univariate analysis. Of these, CCL2 and M-CSF were significant by multivariate analysis. IL-18 levels were significantly higher in MS + disease than MS disease. The LCH patients with BRAF V600E mutation had higher serum levels of CCL7. Conclusion: Numerous inflammatory cytokines and chemokines play a role in LCH. Of those, more specific ones reflect the disease extent (MS vs. SS and MS + vs. MS -) or the BRAF V600E mutation status. It is thought that the most responsible cytokines and chemokines involved in the poor outcome may become future candidate therapeutic targets in LCH.
  • Kazuko Kudo, Hideki Muramatsu, Nao Yoshida, Ryoji Kobayashi, Hiromasa Yabe, Mikiya Endo, Masami Inoue, Yozo Nakazawa, Jun-ichi Hara, Shinji Kaminami, Jiro Inagaki, Yoshiko Hashii, Koji Kato, Ken Tabuchi, Seiji Kojima
    BLOOD 128(22) 2016年12月  
    0
  • Daisuke Tomizawa, Shiro Tanaka, Tadakazu Kondo, Yoshiko Hashii, Yasuyuki Arai, Kazuko Kudo, Takashi Taga, Jiro Inagaki, Katsuyoshi Koh, Masami Inoue, Junji Tanaka, Koji Kato, Yoshiko Atsuta, Souichi Adachi, HIroyuki Ishida
    BLOOD 128(22) 2016年12月  
    0
  • 栗本恭好, 野村小百合, 三浦浩樹, 河村吉紀, 工藤寿子, 吉川哲史, 相澤貴子
    日本小児血液・がん学会雑誌(Web) 53(3) 321‐322(J‐STAGE)-322 2016年10月  
  • Akira Morimoto, Yoko Shioda, Toshihiko Imamura, Kazuko Kudo, Hiroshi Kawaguchi, Kazuo Sakashita, Masahiro Yasui, Yuhki Koga, Ryoji Kobayashi, Eiichi Ishii, Junichiro Fujimoto, Keizo Horibe, Fumio Bessho, Yukiko Tsunematsu, Shinsaku Imashuku
    International Journal of Hematology 104(1) 99-109 2016年7月1日  
    © 2016, The Japanese Society of Hematology. The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was performed to further improve the prognosis from 2002 to 2009. The present study compared the therapeutic results of these two studies in terms of multisystem disease. All patients were treated with 6 weeks of the Induction A regimen, comprising cytarabine, vincristine and prednisolone, followed by maintenance therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has been revised from JLSG-96 in the following respects: prednisolone dosage during Induction A increased; duration of maintenance therapy extended from 24 to 48 weeks; cyclosporine introduced to Induction B for progressive disease. One hundred forty-seven children with multisystem LCH were evaluated. Of these, 84 were positive for risk of organ involvement (RO) and 63 were RO-negative. At the 6-week point, 76.2 % of RO+ and 93.7 % of RO− patients responded to Induction A. Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5–56.9] for RO+ and 69.7 % (58.4–81.1) for RO−, which was significantly superior to that in JLSG-96 [26.8 % (13.3–40.4) and 38.9 % (16.4–61.4), respectively]. The intensified induction and prolonged maintenance regimens in JLSG-02 improved EFS in patients with multisystem LCH.
  • SUZUKI Kyogo, OKUNO Yusuke, KAWASHIMA Nozomu, MURAMATSU Hideki, OKUNO Tatsuya, SEKIYA Yuko, KATAOKA Shinsuke, HAMADA Motoharu, MURAKAMI Norihiro, KOJIMA Daiei, NARITA Kotaro, NARITA Atsushi, SAKAGUCHI Hirotoshi, SAKAGUCHI Kimiyoshi, YOSHIDA Nao, NISHIO Nobuhiro, HAMA Asahito, TAKAHASHI Yoshiyuki, KUDO Kazuko, KATO Koji, KOJIMA Seiji
    臨床血液 57(9) 2016年  
  • 三浦 浩樹, 工藤 寿子, 村松 秀城, 高橋 義行, 小島 勢二, 吉川 哲史
    日本小児血液・がん学会雑誌 52(4) 247-247 2015年10月  
  • 宇菜緒子, 直江篤樹, 安井稔博, 原普二夫, 鈴木達也, 河村吉紀, 工藤寿子, 黒田誠
    日本小児外科学会雑誌 51(2) 290-290 2015年4月20日  
  • Nao Yoshida, Hiromasa Yabe, Kazuko Kudo, Ryoji Kobayashi, Miharu Yabe, Masami Inoue, Mizuka Miki, Hisashi Sakamaki, Koji Kato, Keisei Kawa, Ritsuro Suzuki, Ken-ichiro Watanabe, Seiji Kojima
    BLOOD 124(21) 2014年12月  
  • Yukiko Oh, Akira Morimoto, Yoko Shioda, Toshihiko Imamura, Kazuko Kudo, Shinsaku Imashuku
    CYTOKINE 70(2) 194-197 2014年12月  
    Osteopontin (OPN) acts as an osteoclast activator, a proinflammatory cytokine, and a chemokine attracting histiocytes/monocytes and is abundantly expressed in Langerhans cell histiocytosis (LCH). We investigated whether serum OPN levels are related to disease types in LCH. Fifty-eight newly diagnosed LCH patients were studied; eight with risk organ (liver, spleen and/or hematopoietic) involvements positive multisystem (MS+) disease, 27 with risk organ involvement negative multisystem (MS-) disease and 23 with single system (SS) disease. Pediatric patients with non-inflammatory disease (n = 27) were used as controls. All of patients with MS+ disease were younger than 3 years. Serum OPN levels and 44 kinds of humoral factors were measured by ELISA and Bio-Plex suspension array system, respectively. In the patients younger than 3 years, the median serum OPN level (interquartile range) was 240.3 ng/ml (137.6-456.0) in MS+ (n = 8); 92.7 ng/ml (62.0-213.8) in MS- (n = 14) and 72.5 ng/ml (55.6-94.0) in SS (n = 9) and 74.4 ng/ml (42.2-100.0) in control (n = 12). The OPN values were significantly higher in the MS+ group than the MS-, SS and control groups (p = 0.044, p = 0.001 and p = 0.002, respectively), but not different between the MS-, SS and control groups. In the patients older than 3 years, the median level of serum OPN (IQR) was 56.2 ng/ml (22.9-77.5) in MS- (n = 13), 58.9 ng/ml (31.0-78.7) in SS (n = 14) and 41.9 (28.9-54.1) in control (n = 15). These values did not differ significantly between each group. The serum OPN levels were positively correlated with the serum IL-6, CCL2, IL-18, IL-8 and IL-2 receptor concentration. OPN may be involved in risk organ dissemination and poor prognosis of LCH through the function as inflammatory cytokine/chemokine. (C) 2014 Elsevier Ltd. All rights reserved.
  • Akira Morimoto, Yukiko Oh, Yoko Shioda, Kazuko Kudo, Toshihiko Imamura
    PEDIATRICS INTERNATIONAL 56(4) 451-461 2014年8月  
    The purpose of this review is to provide an updated overview of the pathogenesis and treatment of Langerhans cell histiocytosis (LCH). The pathogenesis of LCH remains obscure and the optimal treatment for LCH has not been established, although incremental progress has been made. Proinflammatory cytokines and chemokines are known to play a role in LCH, which suggests that LCH is an immune disorder. However, the oncogenic BRAF mutation is also detected in more than half of LCH patients, which suggests that LCH is a neoplastic disorder. Remaining major issues in the treatment of LCH are how to rescue patients who have risk-organ involvement but do not respond to first-line therapy, the optimal treatment for the orphan disease of multifocal adult LCH, and how to reduce and treat central nervous system-related consequences, such as central diabetes insipidus and neurodegeneration. More research is needed to better understand the pathogenesis of this disease and to resolve the treatment issues.
  • 梅田雄嗣, 足立壯一, 田中司朗, 小川淳, 畠山直樹, 坂田尚己, 工藤寿子, 五十嵐俊次, 大島久美, 百名伸之, 澤田明久, 加藤剛二, 井上雅美, 熱田由子, 高見昭良, 村田誠
    日本造血細胞移植学会総会プログラム・抄録集 36th 212 2014年2月14日  
  • Marjolein Blink, Martin Zimmermann, Christine von Neuhoff, Dirk Reinhardt, Valerie de Haas, Henrik Hasle, Maureen M. O'Brien, Batia Stark, Julie Tandonnet, Andrea Pession, Katerina Tousovska, Daniel K. L. Cheuk, Kazuko Kudo, Takashi Taga, Jeffrey E. Rubnitz, Iren Haltrich, Walentyna Balwierz, Rob Pieters, Erik Forestier, Bertil Johansson, Marry M. van den Heuvel-Eibrink, C. Michel Zwaan
    HAEMATOLOGICA 99(2) 299-307 2014年2月  査読有り
    Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (+/- 2%), with the overall survival rate being 79% (+/- 2%), the cumulative incidence of relapse 12% (+/- 2%), and the cumulative incidence of toxic death 7% (+/- 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%+/- 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (+/- 2%) (P=0.004). Multivariate analyses revealed that white blood cell count &gt;= 20x10(9)/L and age &gt;3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.
  • Norio Shiba, Kentaro Ohki, Myoung-ja Park, Manabu Sotomatsu, Kazuko Kudo, Etsuro Ito, Masahiro Sako, Hirokazu Arakawa, Yasuhide Hayashi
    BRITISH JOURNAL OF HAEMATOLOGY 164(1) 156-159 2014年1月  査読有り
  • Motohiro Kato, Yoshiyuki Takahashi, Daisuke Tomizawa, Yasuhiro Okamoto, Jiro Inagaki, Katsuyoshi Koh, Atsushi Ogawa, Keiko Okada, Yuko Cho, Junko Takita, Hiroaki Goto, Hisashi Sakamaki, Hiromasa Yabe, Keisei Kawa, Ritsuro Suzuki, Kazuko Kudo, Koji Kato
    Biology of Blood and Marrow Transplantation 19(12) 1690-1694 2013年12月  査読有り
    Recent reports revealed that intravenous (iv) busulfan (BU) may not only reduce early nonrelapse mortality (NRM) but also improve overall survival (OS) probability in adults. Therefore, we retrospectively compared outcomes for 460 children with acute leukemia who underwent hematopoietic stem cell transplantation with either iv-BU (n=198) or oral busulfan (oral-BU) (n=262) myeloablative conditioning. OS at 3years was 53.4%±3.7% with iv-BU and 55.1%±3.1% with oral-BU the difference was not statistically significant (P= 77). OS at 3years in 241 acute lymphoblastic leukemia and 219 acute myeloid leukemia patients was 56.4%±5.5% with iv-BU and 54.6%±4.1 with oral-BU (P= 51) and 51.0%±5.0% with iv-BU and 55.8%±4.8% with oral-BU (P= 83), respectively. Cumulative incidence of relapse at 3years with iv-BU was similar to that with oral-BU (39.0%±3.6% and 36.4%±3.1%, respectively P= 67). Cumulative incidence of NRM at 3years was 16.6%±2.7% with iv-BU and 18.3%±2.5% with oral-BU (P= 51). Furthermore, multivariate analysis showed no significant survival advantage with iv-BU. In conclusion, iv-BU failed to show a significant survival advantage in children with acute leukemia. © 2013 American Society for Blood and Marrow Transplantation.
  • Motohiro Kato, Yoshiyuki Takahashi, Daisuke Tomizawa, Yasuhiro Okamoto, Jiro Inagaki, Katsuyoshi Koh, Atsushi Ogawa, Keiko Okada, Yuko Cho, Junko Takita, Hiroaki Goto, Hisashi Sakamaki, Hiromasa Yabe, Keisei Kawa, Ritsuro Suzuki, Kazuko Kudo, Koji Kato
    BLOOD 122(21) 2013年11月  
  • Daisuke Tomizawa, Akio Tawa, Tomoyuki Watanabe, Akiko Moriya Saito, Kazuko Kudo, Takashi Taga, Shotaro Iwamoto, Akira Shimada, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Hiroyuki Takahashi, Hideki Nakayama, Nobutaka Kiyokawa, Keiichi Isoyama, Shuki Mizutani, Junichi Hara, Keizo Horibe, Tatsutoshi Nakahata, Souichi Adachi
    INTERNATIONAL JOURNAL OF HEMATOLOGY 98(5) 578-588 2013年11月  査読有り
    Infants (&lt; 1 year old) with acute myeloid leukemia (AML) are particularly vulnerable to intensive cytotoxic therapy. Indeed, the mortality rate was high among infants enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study, which prompted us to temporarily suspend patient enrollment and amend the protocol. Forty-five infants with AML were enrolled. For patients aged &lt; 2 years, drug doses were adjusted for body weight. Following the protocol amendments, doses for infants were reduced by a further 33 % in the initial induction course. Six infants died during the induction phase (including five early deaths), mainly due to pulmonary complications. The 3-year probability of overall survival (pOS) in all 45 infants [55.9 %, 95 % confidence interval (CI) 37.9-70.6 %] was significantly lower than that of patients aged 1 to &lt; 2 years (77.0 %, 95 % CI 62.7-86.3 %) and those aged a parts per thousand yen2 years (74.7 %, 95 % CI 69.2-79.4 %) (P = 0.037), mainly due to the higher non-relapse mortality rate in infants. No early deaths occurred after the protocol amendments, and the 3-year pOS of the 17 infants enrolled thereafter was 76.4 % (95 % CI 48.8-90.4 %). In conclusion, appropriate dose reduction is essential to avoid early deaths when treating infants with AML.
  • Y. Hara, N. Shiba, A. Shimada, K. Kudo, D. Tomizawa, T. Taga, K. Horibe, S. Adachi, H. Arakawa, A. Tawa, Y. Hayashi
    PEDIATRIC BLOOD & CANCER 60 5-6 2013年9月  
  • Wang Runan, Yoshida Kenichi, Okuno Yusuke, Sato-Otsubo Aiko, Toki Tsutomu, Kudo Kazuko, Kanezaki Rika, Shiraishi Yuichi, Chiba Kenichi, Terui Kiminori, Sato Tomohiko, Iribe Yuji, Ohga Shouichi, Kuramitsu Madoka, Hamaguchi Isao, Ohara Akira, Kamimaki Isamu, Hara Junichi, Sugita Kanji, Matsubara Kousaku, Koike Kenichi, Ishiguro Akira, Kawano Yoshifumi, Kanno Hitoshi, Kojima Seiji, Sawada Takafumi, Uechi Tamayo, Kenmochi Naoya, Miyano Satoru, Ogawa Seishi, Ito Etsuro
    臨床血液 54(9) 1107-1107 2013年9月  
  • Shiba Norio, Hara Yusuke, Park Myoug-Ja, Ohki Kentaro, Fukushima Keitaro, Sako Masahiko, Kudo Kazuko, Arakawa Hirokazu, Ito Etsurou, Hayashi Yasuhide
    臨床血液 54(9) 1210-1210 2013年9月  
  • Atsushi Narita, Hideki Muramatsu, Hirotoshi Sakaguchi, Sayoko Doisaki, Makito Tanaka, Asahito Hama, Akira Shimada, Yoshiyuki Takahashi, Nao Yoshida, Kimikazu Matsumoto, Koji Kato, Kazuko Kudo, Yoko Furukawa-Hibi, Kiyofumi Yamada, Seiji Kojima
    JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY 35(5) E219-E223 2013年7月  査読有り
    Background: Voriconazole is a triazole antifungal agent with potent activity against a broad spectrum of pathogens, including Aspergillus and Candida species. In human adults, allelic polymorphisms of CYP2C19 are known to correlate with significant variation in voriconazole plasma concentration. Here, we report an analysis of CYP2C19 phenotype and voriconazole plasma concentrations in children. Methods: This retrospective study included 37 children who had voriconazole plasma concentrations measured from May 2006 to June 2011. All had single-nucleotide polymorphisms that define the 3 major CYP2C19 alleles. Patients were classified as follows: normal metabolizers, intermediate metabolizers, poor metabolizers, or hypermetabolizers. Results: The frequencies of the 3 CYP2C19 genetic polymorphisms were similar to those previously reported for Japanese adults. Trough plasma concentrations of voriconazole were significantly higher in the poor metabolizer and intermediate metabolizer groups compared with the normal metabolizer and hypermetabolizer groups (P=0.004). Two patients with high plasma concentrations experienced voriconazole-related severe adverse events (syndrome of inappropriate antidiuretic hormone secretion and cardiac toxicities). Conclusions: The current study suggests that a significant association exists in children between the voriconazole plasma concentration and the CYP2C19 phenotype. Dose adjustment based on CYP2C19 phenotype may be useful during voriconazole therapy, especially for Japanese children, who as a group have a higher incidence of the poor metabolizer and intermediate metabolizer phenotypes.
  • 村松秀樹, 坂口大俊, 富沢大輔, 岡本康裕, 井上雅美, 稲垣二郎, 気賀沢寿人, 加藤剛二, 矢部普正, 河敬世, 熱田由子, 工藤寿子
    日本造血細胞移植学会総会プログラム・抄録集 35th 196 2013年2月8日  
  • 原 勇介, 柴 徳生, 嶋田 明, 工藤 寿子, 富澤 大輔, 多賀 崇, 多和 昭雄, 荒川 浩一, 足立 壮一, 林 泰秀
    日本小児科学会雑誌 117(2) 344-344 2013年2月  
  • 竹内秀輔, 鈴木涼子, 福島敬, 福島紘子, 岩淵敦, 中尾朋平, 山口玲子, 工藤寿子, 杉田真太朗, 稲留征典, 佐藤豊実, 櫻井英幸, 金子道夫, 須磨崎亮
    小児血液・がん学会雑誌 50(2) 269-273 2013年  査読有り
  • Yoshiyuki Takahashi, Hideki Muramatsu, Naoki Sakata, Nobuyuki Hyakuna, Kazuko Hamamoto, Ryoji Kobayashi, Etsuro Ito, Hiroshi Yagasaki, Akira Ohara, Akira Kikuchi, Akira Morimoto, Hiromasa Yabe, Kazuko Kudo, Ken-ichiro Watanabe, Shouichi Ohga, Seiji Kojima
    BLOOD 121(5) 862-863 2013年1月  査読有り
  • Yoshiyuki Takahashi, Akira Ohara, Ryoji Kobayashi, Hiromasa Yabe, Akira Kikuchi, Hiroshi Yagasaki, Akira Morimoto, Ken-ichiro Watanabe, Etsuro Ito, Kazuko Kudo, Akinari Fukuda, Seisuke Sakamoto, Mureo Kasahara, Atsuko Nakazawa, Seiji Kojima
    BLOOD 120(21) 2012年11月  
  • Norio Shiba, Kenichi Yoshida, Yusuke Okuno, Yuichi Shiraishi, Yasunobu Nagata, Kentarou Ohki, Motohiro Kato, Myoung-ja Park, Junko Takita, Takashi Kanazawa, Kazuko Kudo, Hirokazu Arakawa, Etsuro Ito, Masashi Sanada, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
    BLOOD 120(21) 2012年11月  
  • Etsuro Ito, Kenichi Yoshida, Yusuke Okuno, Aiko Sato-Otsubo, Tsutomu Toki, Satoru Miyano, Yuichi Shiraishi, Kenichi Chiba, Kiminori Terui, RuNan Wang, Tomohiko Sato, Yuji Iribe, Shouichi Ohga, Madoka Kuramitsu, Isao Hamaguchi, Akira Ohara, Kazuko Kudo, Isamu Kamimaki, Junichi Hara, Kanji Sugita, Kousaku Matsubara, Kenichi Koike, Akira Ishiguro, Yoshifumi Kawano, Hitoshi Kanno, Seiji Kojima, Seishi Ogawa
    BLOOD 120(21) 2012年11月  
  • Takashi Taga, Akiko Moriya Saito, Kazuko Kudo, Daisuke Tomizawa, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Shotaro Iwamoto, Hideki Nakayama, Hiroyuki Takahashi, Akio Tawa, Akira Shimada, Tomohiko Taki, Hisato Kigasawa, Katsuyoshi Koh, Souichi Adachi
    BLOOD 120(9) 1810-1815 2012年8月  査読有り
    Myeloid leukemia in Down syndrome (ML-DS) is associated with good response to chemotherapy and favorable prognosis. Because little research has been focused on refractory/relapsed (R/R) cases, we conducted a retrospective analysis for R/R ML-DS. Among ML-DS patients diagnosed between 2000 and 2010 in Japan, 26 relapsed (25 in the BM and 1 in the skin), and 3 refractory patients were enrolled. The male/female ratio was 18/11. The median age at initial diagnosis of ML-DS was 2 years, and the median time to relapse was 8.6 months. Each patient initially had been treated with ML-DS-specific protocols. Thirteen of the 26 patients achieved complete remission with various kinds of reinduction chemotherapies; 2 of 8 survived without further recurrence after receiving allogeneic hematopoietic stem cell transplantation, and 4 of 5 maintained complete remissions with chemotherapy alone. Treatment failures mostly were associated with disease progression rather than treatment-related toxicities. The 3-year OS rate was 25.9% +/- 8.5%. A longer duration from initial diagnosis to relapse was a significant favorable prognostic factor (P &lt; .0001). We conclude that clinical outcome for patients with R/R ML-DS generally are unfavorable, even in those receiving hematopoietic stem cell transplantation. Novel methods to identify poor prognostic factors for ML-DS are necessary. (Blood. 2012;120(9):1810-1815)
  • Takeshi Asano, Kazuhiro Kogawa, Akira Morimoto, Yasushi Ishida, Nobuhiro Suzuki, Shouichi Ohga, Kazuko Kudo, Shigeru Ohta, Hiroshi Wakiguchi, Ken Tabuchi, Shunichi Kato, Eiichi Ishii
    PEDIATRIC BLOOD & CANCER 59(1) 110-114 2012年7月  査読有り
    Background Hemophagocytic lymphohistiocytosis (HLH) is associated with hypercytokinemia in children. Although HLH can be also observed after hematopoietic stem cell transplantation (HSCT), the incidence and clinical features of HLH after HSCT remain obscure. Procedure The clinical features of HLH after HSCT (post-HSCT HLH) were investigated in children with malignancies, immune deficiencies, or aplastic anemia. The HLH/Langerhans Cell Histiocytosis (LCH) Committee of the Japanese Society of Pediatric Hematology (JSPH) sent questionnaires to hospitals with JPSH members asking for details of cases in which HLH occurred after HSCT between 1998 and 2008. Results Among 42 children who were diagnosed with post-HSCT HLH between 1998 and 2008 in Japan, 37 fulfilled our inclusion criteria; of these, 26 were classified as early-onset (onset &lt;30 days after HSCT) and 11 were classified as late-onset (onset &gt;30 days after HSCT). In the early-onset group, the presence of respiratory symptoms, high levels of total bilirubin, and triglycerides at onset and the lack of control of GVHD with tacrolimus were significantly associated with non-resolution of HLH (P?&lt;?0.05). The survival rate was significantly higher in patients with resolution of HLH than in those without resolution (59% vs. 14%, P?&lt;?0.05). Conclusions These findings suggest that early-onset post-HSCT HLH is a specific entity of HLH, and appropriate diagnosis and prompt management need to be established. Pediatr Blood Cancer 2012; 59: 110114. (C) 2011 Wiley Periodicals, Inc.
  • Hirotoshi Sakaguchi, Yoshiyuki Takahashi, Nobuhiro Watanabe, Sayoko Doisaki, Hideki Muramatsu, Asahito Hama, Akira Shimada, Hiroshi Yagasaki, Kazuko Kudo, Seiji Kojima
    PEDIATRIC BLOOD & CANCER 58(5) 780-784 2012年5月  査読有り
    Background Idiopathic pneumonia syndrome (IPS) is a severe complication that can occur after hematopoietic stem cell transplantation (HSCT) and is often associated with a fatal outcome despite intensive supportive care. Procedure. To assess the incidence and risk factors of IPS, we reviewed 251 consecutive patients (median age, 7.0 years) who received HSCT at the Department of Pediatrics, Nagoya University Hospital, between January 1990 and July 2009. Results. Twenty of 251 (cumulative incidence of IPS at 2 years after HSCT, 8.0%; 95% confidence interval (CI), 5.1-12.4%) patients developed IPS. The median duration from HSCT to diagnosis of IPS was 67 days (range, 12-486 days). Patients with IPS had significantly higher 5-year transplant-related mortality compared to patients without IPS (52% (95% CI, 19-77%) vs. 13% (95% CI, 5-25%), P < 0.001), and the probability of 5-year overall survival was significantly worse for patients with IPS (42% (95% CI, 25-64%) vs. 68% (95% CI, 59-76%), P = 0.01). By multivariate analysis, high risk in underlying disease (HR, 2.5; 95% CI, 1.0-6.7; P = 0.05) and a busulfan-containing regimen (HR, 3.5; 95% CI, 1.3-9.9; P < 0.01) were identified as the independent risk factors for developing IPS. Conclusion. The prophylactic strategies for IPS in patients with these risk factors were warranted. Pediatr Blood Cancer 2012;58:780-784. (C) 2011 Wiley Periodicals, Inc.
  • Madoka Kuramitsu, Aiko Sato-Otsubo, Tomohiro Morio, Masatoshi Takagi, Tsutomu Toki, Kiminori Terui, RuNan Wang, Hitoshi Kanno, Shouichi Ohga, Akira Ohara, Seiji Kojima, Toshiyuki Kitoh, Kumiko Goi, Kazuko Kudo, Tadashi Matsubayashi, Nobuo Mizue, Michio Ozeki, Atsuko Masumi, Haruka Momose, Kazuya Takizawa, Takuo Mizukami, Kazunari Yamaguchi, Seishi Ogawa, Etsuro Ito, Isao Hamaguchi
    BLOOD 119(10) 2376-2384 2012年3月  査読有り
    Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs). To identify new mutations, we investigated large deletions in the RP genes RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients (25.9%) possessing mutations that were not detected by sequencing. Among these large deletions, similar results were obtained with 6 of 7 patients screened with a single nucleotide polymorphism array. We found an extensive intragenic deletion in RPS19, including exons 1-3. We also found 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. In particular, the large deletions in the RPL5 and RPS17 alleles are novel. All patients with a large deletion had a growth retardation phenotype. Our data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes. (Blood. 2012;119(10):2376-2384)
  • 岡本康裕, 石田宏之, 田渕腱, 富澤大輔, 多賀崇, 工藤寿子, 井上雅美, 稲垣二郎, 加藤剛二, 康勝好, 矢部普正, 坂巻壽, 河敬世, 熱田由子
    日本造血細胞移植学会総会プログラム・抄録集 34th 231 2012年2月1日  
  • 石田宏之, 足立壮一, 長谷川大一郎, 岡本康裕, 気賀沢寿人, 稲垣二郎, 井上雅美, 康勝好, 矢部普正, 河敬世, 加藤剛二, 坂巻壽, 熱田由子, 工藤寿子
    日本造血細胞移植学会総会プログラム・抄録集 34th 232 2012年2月1日  
  • 野村明孝, 堀越泰雄, 阿部泰子, 小倉妙美, 高嶋能文, 植田育也, 稲員恵美, 工藤寿子
    小児血液・がん学会雑誌 49(3) 387-392 2012年  査読有り
  • Yoko Shioda, Souichi Adachi, Shinsaku Imashuku, Kazuko Kudo, Toshihiko Imamura, Akira Morimoto
    INTERNATIONAL JOURNAL OF HEMATOLOGY 94(6) 545-551 2011年12月  査読有り
    To determine the ability of recent systemic chemotherapy protocols to reduce the incidence of central diabetes insipidus (CDI) in Langerhans cell histiocytosis (LCH), 43 CDI cases that belonged to a cohort of 348 pediatric patients with multi-focal LCH who were treated with the JLSG-96/-02 protocols were analyzed. The overall incidence of CDI was 12.4%, but in 24 cases CDI was already present at the time LCH was diagnosed. Thus, CDI developed during or after systemic chemotherapy over a follow-up period of 5.0 (0.2-14.7) years in only 19 patients (5.9%), with 7.4% at 5-year cumulative risk by Kaplan-Meier analysis. In two cases, complete resolution of CDI was noted. Anterior pituitary hormone deficiency was detected in 13 cases, while CDI-associated neurodegenerative disease was observed in six cases. The JLSG-96/-02 protocol appears to effectively reduce the occurrence of CDI. However, novel therapeutic measures are required to reverse pre-existing CDI and to prevent CDI-associated neurological complications.
  • Atsushi Manabe, Hirohide Kawasaki, Motoaki Chin, Atsushi Sato, Kimikazu Matsumoto, Tsutomu Watanabe, Michiko Kajiwara, Hiroyuki Shimada, Itaru Kato, Yuichi Kodama, Noriko Sato, Kazuko Kudo, Atsushi Kikuta, Megumi Oda, Tomoyuki Watanabe, Akiko M. Saito, Masahito Tsurusawa, Keizo Horibe
    BLOOD 118(21) 1095-1096 2011年11月  
  • Hideki Muramatsu, Hiromasa Yabe, Ryoji Kobayashi, Akira Kikuchi, Kazuko Kudo, Keisei Kawa, Koji Kato, Ritsuro Suzuki, Yoshiyuki Takahashi, Jiro Inagaki, Masami Inoue, Seiji Kojima
    BLOOD 118(21) 379-379 2011年11月  
  • Keisuke Kato, Yasuko Kojima, Chie Kobayashi, Kazumasa Mitsui, Ryoko Nakajima-Yamaguchi, Kazuko Kudo, Toshihiro Yanai, Ai Yoshimi, Tomohei Nakao, Tomohiro Morio, Mureo Kasahara, Kazutoshi Koike, Masahiro Tsuchida
    INTERNATIONAL JOURNAL OF HEMATOLOGY 94(5) 479-482 2011年11月  査読有り
    We report two patients with chronic granulomatous disease (CGD). The first patient presented with granulomatous colitis and pulmonary aspergillosis, and the second patient with liver abscess and restrictive pulmonary disorder. Both patients underwent allogeneic hematopoietic stem cell transplantation, the first from an HLA-matched sibling donor, and the second from an HLA-matched unrelated donor, after preconditioning with fludarabine, anti-thymocyte globulin, cyclophosphamide, and total-body irradiation of 3 Gy. The engraftment was prompt and the regimen-related toxicity was mild. The patients are able to return to their daily lives with full donor chimerism, although the second patient underwent a living-related-donor orthotopic liver transplantation from his mother for chronic liver graft-versus-host disease. The conditioning regimen we used was feasible and applicable to patients with CGD accompanied by inflammatory disease and severe infection.
  • Nobuhiro Watanabe, Yoshiyuki Takahashi, Kimikazu Matsumoto, Yasuo Horikoshi, Asahito Hama, Hideki Muramatsu, Nao Yoshida, Hiroshi Yagasaki, Kazuko Kudo, Keizo Horibe, Koji Kato, Seiji Kojima
    PEDIATRIC TRANSPLANTATION 15(6) 642-649 2011年9月  査読有り
    Although some studies have reported that TBI and MEL offer an effective conditioning regimen for autologous SCT in acute leukemia, little has been reported regarding outcomes of allogeneic SCT. We retrospectively evaluated outcomes for 50 pediatric patients who underwent allo-SCT conditioned with intravenous MEL (180-210 mg/m(2)) and fractionated TBI (12-13.2 Gy) from HLA-identical related donors. Nineteen patients were in CR1, 18 were in CR2, and 13 showed advanced-stage disease (&gt;= CR3). Patients had received allo-SCT from HLA-identical siblings (n = 45) or phenotypically HLA-identical family donors (n = 5). Median duration of follow-up for all disease-free patients was 61 months (range, 8.8-177 months). At the time of analysis, 12 patients had died. Eleven of those died of relapse, and one died of TRM. DFS rates for all patients, patients with AML (n = 12), and patients with lymphoid malignancy (n = 38) were 61.4% and 82.1%, respectively. DFS rates for CR1, CR2, and &gt;= CR3 cases were 89.2%, 88.1%, and 23.1%, respectively (p &lt; 0.05). MEL/TBI for pediatric patients with hematological malignancies was associated with lower relapse rates and no increase in toxicity, resulting in better survival.

講演・口頭発表等

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共同研究・競争的資金等の研究課題

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