研究者詳細 - 鷲尾　佳奈

論文 - 鷲尾　佳奈

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Paediatric anaplastic large-cell lymphoma with cardiac tamponade. 国際誌

Takahiro Shiwaku, Kosuke Tamefusa, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Hirokazu Tsukahara

British journal of haematology 2025年1月

Tectal glioma: clinical, radiological, and pathological features, and the importance of molecular analysis. 査読

Ryoji Imoto, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Naoya Kemmotsu, Yasuki Suruga, Ryo Mizuta, Yasuhito Kegoya, Yohei Inoue, Tsuyoshi Umeda, Madoka Hokama, Kana Washio, Hiroyuki Yanai, Shota Tanaka, Kaishi Satomi, Koichi Ichimura, Isao Date

Brain tumor pathology 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5 years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation.

DOI： 10.1007/s10014-024-00494-9

Alectinib maintenance therapy following cord blood transplantation for relapsed pediatric anaplastic large cell lymphoma with central nervous system involvement. 査読国際誌

Kosuke Tamefusa, Hisashi Ishida, Daisuke Miyahara, Takahiro Shiwaku, Motoharu Ochi, Kiichiro Kanamitsu, Kaori Fujiwara, Yasuhisa Tatebe, Kana Washio, Tomoyuki Akiyama, Hirokazu Tsukahara

Annals of hematology 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pediatric ALK-positive anaplastic large cell lymphoma is a rare subtype of non-Hodgkin lymphoma, and approximately 30% of patients relapse following treatment with conventional chemotherapy. Alectinib monotherapy has demonstrated excellent activity in relapsed and refractory ALCL, but its role as a maintenance therapy after hematopoietic cell transplantation is unclear. We experienced a relapse case of pediatric ALK-positive ALCL with central nervous system involvement treated with alectinib maintenance therapy following cord blood transplantation. The patient has maintained complete remission for more than 3 years after transplantation. There were no remarkable adverse effects that led to discontinuation of alectinib.

DOI： 10.1007/s00277-024-06000-7

腎移植後リンパ増殖症に対して,rituximab反応性による治療層別化レジメンを使用した小児例

爲房宏輔, 石田悠志, 藤原かおり, 塩飽孝宏, 吉永香澄, 西村慎吾, 鷲尾佳奈, 荒木元朗, 塚原宏一

臨床血液 65 ( 5 ) 466 - 466 2024年5月

小児急性白血病患者における輸血療法の後方視的検討査読

鷲尾佳奈, 塩飽孝宏, 爲房宏輔, 石田悠志, 藤原かおり, 塚原宏一

臨床血液 65 ( 5 ) 459 - 459 2024年5月

当院で経験したDiffuse midline glioma,H3K27-alteredの臨床的特徴

外間まどか, 大谷理浩, 石田穣治, 梅田剛志, 井上陽平, 水田亮, 井本良二, 駿河和城, 劒持直也, 家護谷泰仁, 平野秀一郎, 冨田祐介, 藤井謙太郎, 鷲尾佳奈, 田中將太

小児の脳神経 49 ( 2 ) 209 - 209 2024年4月

当院で経験したDiffuse midline glioma,H3K27-alteredの臨床的特徴

外間まどか, 大谷理浩, 石田穣治, 梅田剛志, 井上陽平, 水田亮, 井本良二, 駿河和城, 劒持直也, 家護谷泰仁, 平野秀一郎, 冨田祐介, 藤井謙太郎, 鷲尾佳奈, 田中將太

小児の脳神経 49 ( 2 ) 209 - 209 2024年4月

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review. 査読国際誌

Yasuhito Kegoya, Yoshihiro Otani, Yohei Inoue, Ryo Mizuta, Fumiyo Higaki, Kana Washio, Shinichiro Koizumi, Kazuhiko Kurozumi, Joji Ishida, Kentaro Fujii, Norio Yamamoto, Yoshihiro Tanaka, Isao Date

Journal of neuro-oncology 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.

DOI： 10.1007/s11060-024-04587-5

Letermovir at a Prophylactic Dose for Cytomegalovirus Infection in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in Japan. 査読

Yasuhisa Tatebe, Yohei Manabe, Yuta Tanaka, Takahiro Shiwaku, Motoharu Ochi, Kosuke Tamefusa, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Hirofumi Hamano, Kiminaka Murakawa, Yoshito Zamami

Biological & pharmaceutical bulletin 47 ( 9 ) 1575 - 1582 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Cytomegalovirus (CMV) infection is a major complication of hematopoietic stem cell transplantation (HSCT). Previous studies in adults demonstrated that letermovir prophylaxis for 100 d after HSCT reduces the occurrence of CMV infection; however, studies in children are limited. In this study, we aimed to examine the incidence of CMV infection in children who underwent allogeneic HSCT with prophylactic letermovir therapy. A single-center retrospective study was conducted among patients aged ≤17 who underwent allogeneic HSCT. We compared the cumulative incidence of CMV infection, mainly monitored by pp65-antigenemia, after HSCT between patients with and without letermovir prophylaxis (10-12 or 5-6 mg/kg/d when co-administered with cyclosporine) using Gray's test. We analyzed 79 patients with a median follow-up period of 126 d. The median age of these patients was 8.3 years (Interquartile range, 3.7-12.4). Prophylactic letermovir was used in 25 patients. Twenty-five patients developed CMV infection, and the cumulative incidence was 38.9% (95% confidence intervals, 25.0-52.5). The cumulative incidence of CMV infection was not significantly different between the letermovir and no-letermovir groups (33.1 vs. 36.6%, p = 0.228). Meanwhile, the cumulative incidence of CMV infection up to 100 d following HSCT was significantly lower in the letermovir group than in the no-letermovir group (8.0 vs. 32.8%, p = 0.026). Most patients experienced no noticeable adverse effects associated with letermovir; however, one patient discontinued letermovir because of nausea and anorexia. In conclusion, the results of this study suggest that letermovir prophylaxis against CMV infection may be effective in children without severe adverse effects.

DOI： 10.1248/bpb.b24-00217

Delayed diagnostic interval and survival outcomes in pediatric leukemia: A single‐center, retrospective study 査読

Kosuke Tamefusa, Motoharu Ochi, Hisashi Ishida, Takahiro Shiwaku, Kiichiro Kanamitsu, Kaori Fujiwara, Yasuhisa Tatebe, Naomi Matsumoto, Kana Washio, Hirokazu Tsukahara

European Journal of Haematology 2023年12月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Abstract

Objective

This study primarily focused on the diagnostic interval (DI), defined as the duration from the onset of leukemic symptoms to diagnosis. We investigated whether a prolonged DI is associated with the outcomes of pediatric leukemia.

Methods

We retrospectively collected data of children with newly diagnosed pediatric leukemia at Okayama University Hospital from January 2007 to December 2022. Survival analyses were conducted using Kaplan–Meier methods, and an unadjusted analysis to compare differences in survival was performed using the log‐rank test.

Results

In total, 103 children with leukemia were included in the analysis. The median DI was 20 days (interquartile range, 9.5–33.5 days). A prolonged DI (≥30 days) demonstrated no association with either 5‐year event‐free survival (70.1% for <30 days and 68.3% for ≥30 days, p = .99, log‐rank test) or overall survival (84.7% for <30 days and 89.4% for ≥30 days, p = .85, log‐rank test).

Conclusions

A prolonged DI was not associated with the survival of children with leukemia. If a precise classification of leukemia biology is provided for pediatric patients, a prolonged DI may have little impact on the prognosis of these patients.

DOI： 10.1111/ejh.14162

造血細胞移植後の肝障害の鑑別にMRIが有用であった輸血後鉄過剰症の2小児例査読

鷲尾佳奈, 塩飽孝宏, 爲房宏輔, 越智元春, 石田悠志, 金光喜一郎, 藤原かおり, 塚原宏一

日本輸血細胞治療学会誌 69 ( 5 ) 605 - 609 2023年10月

担当区分：筆頭著者記述言語：日本語出版者・発行元：一般社団法人日本輸血・細胞治療学会

小児がん患者における輸血後鉄過剰症については，海外からは報告が散見される．成人と同様，白血病等における同種造血細胞移植患者において，移植前の血清フェリチン値と合併症の相関等が議論されているが，日本国内からはまだまとまった報告はない．我々は，肝障害を来し，輸血後鉄過剰症と肝移植片対宿主病（GVHD）との鑑別に磁気共鳴画像（MRI）が有用であった2例を経験した．2例とも急性骨髄性白血病であり，肝GVHDとして免疫抑制療法等を行ったにもかかわらず遷延する肝障害を呈していた．高フェリチン血症を認めたためMRI撮像したところ，高度鉄沈着を示唆する所見を呈した．輸血後鉄過剰症として鉄キレート療法を行って肝障害が改善した．小児がん患者において，骨髄抑制期間が長く頻回の輸血を要するような症例では，急性期に臓器障害を伴う輸血後鉄過剰症を示す可能性があるが，治療介入の指針や時期については明らかになっていない．今後日本国内でも大規模な調査が必要と思われる．

DOI： 10.3925/jjtc.69.605

濃縮クエン酸溶液を使用し抗凝固比の変更を行ったアフェレーシスの安全性と有効性に関する後方視的解析

藤井敬子, 福見拓也, 阿部将也, 浦田知宏, 清家圭介, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 松岡賢市, 藤井伸治, 鷲尾佳奈, 前田嘉信

日本血液学会学術集会 85回 687 - 687 2023年10月

A Boy Safely Treated with Tyrosine Kinase Inhibitors for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with Osteolysis. 査読

Takahiro Shiwaku, Hisashi Ishida, Yasuhisa Tatebe, Kosuke Tamefusa, Motoharu Ochi, Kaori Fujiwara, Toshihide Kubo, Eiji Nakata, Kana Washio, Hirokazu Tsukahara

Acta medica Okayama 77 ( 4 ) 439 - 442 2023年8月

記述言語：英語

A three-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ALL) presented with an osteolytic lesion in his right upper arm. Tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are an essential component throughout the course of treatment for Ph+ALL. However, TKIs are reported to affect the bone metabolism. In the treatment course of the current patient, the osteolytic lesion quickly improved despite the continuous use of TKIs, even during the concomitant use of corticosteroids. This suggests that TKIs can be safely given with concomitant corticosteroids to children with Ph+ALL, even when osteolytic lesions are present.

DOI： 10.18926/AMO/65757

Optimizing transplantation procedures through identification of prognostic factors in second remission for children with acute myeloid leukemia with no prior history of transplant. 査読国際誌

Hisashi Ishida, Shin-Ichi Tsujimoto, Daisuke Hasegawa, Hirotoshi Sakaguchi, Shohei Yamamoto, Masakatsu Yanagimachi, Katsuyoshi Koh, Akihiro Watanabe, Asahito Hama, Yuko Cho, Kenichiro Watanabe, Maiko Noguchi, Masanobu Takeuchi, Junko Takita, Kana Washio, Keisuke Kato, Takashi Koike, Yoshiko Hashii, Ken Tabuchi, Moeko Hino, Yoshiko Atsuta, Yasuhiro Okamoto

Haematologica 2023年7月

Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch 査読

Takumi Kondo, Keiko Fujii, Nobuharu Fujii, Yuichi Sumii, Tomohiro Urata, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken‐ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 2023年6月

Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma. 査読

Keigo Makino, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Yasuki Suruga, Kana Washio, Kenji Nishida, Hiroyuki Yanai, Shuta Tomida, Daisuke Ennishi, Isao Date

Acta medica Okayama 77 ( 3 ) 323 - 330 2023年6月

記述言語：英語

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.

DOI： 10.18926/AMO/65502

下大静脈腫瘍進展を伴った左腎明細胞肉腫の一例

谷本光隆, 野田卓男, 尾山貴徳, 宮田将徳, 鷲尾佳奈, 越智元春

日本小児泌尿器科学会雑誌 32 ( 2 ) 333 - 333 2023年6月

Three Cases of Down Syndrome with Transient Abnormal Myelopoiesis who Underwent Liver Biopsy before Induction of Low-Dose Cytarabine. 査読

Kana Washio, Kosuke Tamefusa, Motoharu Ochi, Kiichiro Kanamitsu, Hisashi Ishida, Kaori Fujiwara, Kenji Nishida, Kei Tamai, Yosuke Washio, Junko Yoshimoto, Takuo Noda, Hirokazu Tsukahara

Acta medica Okayama 77 ( 2 ) 215 - 220 2023年4月

担当区分：筆頭著者記述言語：英語

Among patients with transient abnormal myelopoiesis (TAM) associated with Down syndrome, approximately 20% die within 6 months from multiorgan failure, especially liver fibrosis. We experienced three children with TAM who had low white blood cell counts but increased bilirubin levels. Here, we discuss the detailed clinical courses of these patients, including the pathological findings of liver biopsies. Our cases, together with previous literature, suggest that liver biopsy can be performed safely and provides useful information, especially regarding disease activities, and that low-dose cytarabine is a reasonable option to prevent early death in TAM patients with liver dysfunction.

DOI： 10.18926/AMO/65153

Posttransplant gilteritinib maintenance therapy for pediatric acute myeloid leukemia with myelodysplasia-related changes with FLT3-internal tandem duplication. 査読国際誌

Kosuke Tamefusa, Hisashi Ishida, Kiichiro Kanamitsu, Motoharu Ochi, Kaori Fujiwara, Yasuhisa Tatebe, Michinori Aoe, Seishiro Nodomi, Kana Washio

Pediatric blood & cancer 70 ( 4 ) e30108 2022年12月

Neonatal hemochromatosis with εγδβ-thalassemia: a case report and analysis of serum iron regulators. 国際誌

Mitsuru Tsuge, Aya Kodera, Hiromi Sumitomo, Tooru Araki, Ryuichi Yoshida, Kazuya Yasui, Hiroki Sato, Yosuke Washio, Kana Washio, Kenji Shigehara, Masato Yashiro, Takahito Yagi, Hirokazu Tsukahara

BMC pediatrics 22 ( 1 ) 622 - 622 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. CASE PRESENTATION: A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. CONCLUSIONS: We reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

DOI： 10.1186/s12887-022-03706-3

造血幹細胞移植後患者に対する就労支援と就学支援体制(実態調査)

鴨井千尋, 西森久和, 鷲尾佳奈, 藤井伸治, 前田嘉信

日本造血・免疫細胞療法学会雑誌 11 ( 4 ) 199 - 205 2022年10月

記述言語：日本語出版者・発行元：(一社)日本造血・免疫細胞療法学会

造血幹細胞移植患者に対する就労支援と就学支援の2021年現在の実践状況を明らかにするため,中国地方の血液内科と小児血液腫瘍科の25施設31名の医師にアンケートを送付し,18施設,23名(74%)から回答を得た。就労支援の窓口は12施設(67%)が開設していたが,相談件数は半数以上が年間0件であった。自施設の就労支援体制について十分であると評価したのはわずか3名(14%)であった。就学支援の経験がある血液内科医は17名中3名(18%)と少なかった。7名(41%)がオンライン授業の経験があると回答した。自施設の高校生・大学生の就学支援体制について全ての施設が十分でないと回答した。これらの結果により,就労・就学支援体制は施設により差があり,改善の余地があることが明らかになった。多職種,他機関との協力関係を構築し,AYA世代を含む全ての患者を支援する体制の必要性が示唆された。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J07578&link_issn=&doc_id=20221028330002&doc_link_id=1390293788341809920&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390293788341809920&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

Low‐dose acyclovir for prophylaxis of varicella‐zoster virus reactivation after hematopoietic stem cell transplantation in children 査読

Yasuhisa Tatebe, Soichiro Ushio, Satoru Esumi, Hikaru Sada, Motoharu Ochi, Kosuke Tamefusa, Hisashi Ishida, Kaori Fujiwara, Kiichiro Kanamitsu, Kana Washio, Risa Katsube, Kiminaka Murakawa, Yoshito Zamami

Pediatric Blood & Cancer 2022年9月

The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology. 査読国際誌

Yasuki Suruga, Kaishi Satomi, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Atsuhito Uneda, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Naoya Kemmotsu, Ryoji Imoto, Ryo Mizuta, Yusuke Tomita, Takao Yasuhara, Kana Washio, Hiroyuki Yanai, Yuko Matsushita, Yuko Hibiya, Akihiko Yoshida, David Capper, Koichi Ichimura, Isao Date

Journal of neuro-oncology 160 ( 1 ) 179 - 189 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

DOI： 10.1007/s11060-022-04131-3

Red blood cell depletion in small-volume bone marrow processing using manipulation with third-party red blood cells: A comparison of the performance of the COBE spectra and the spectra Optia systems. 国際誌

Yuichi Sumii, Nobuharu Fujii, Keiko Fujii, Takumi Kondo, Tomohiro Urata, Maiko Kimura, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 62 ( 9 ) 1829 - 1838 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: For pediatric recipients, red blood cells (RBCs) are added to bone marrow (BM) collections before low RBC volume BM processing using COBE Spectra (COBE) or Spectra Optia (Optia). However, the processing efficiency of this approach has not been evaluated. This study aimed to evaluate RBC depletion and nucleated cell subpopulation recovery rates in third-party RBC-manipulated BM products processed with the COBE or Optia. STUDY DESIGN AND METHODS: We retrospectively collected data on RBC depletion from low RBC volume BM with third-party RBCs (manipulated group) and on conventional large-volume, BM (unmanipulated group) processing performed between September 2010 and December 2021. All procedures were performed using COBE or Optia. RESULTS: The median residual RBC volume in the manipulated group was 9.5 ml in COBE and 2.5 ml in Optia (p = .01). The median total nucleated cell (TNC) and mononuclear cell (MNC) were comparable between the manipulated groups using each cell separator (TNC, 40.8 vs. 47.1%; MNC, 78.3 vs. 79.4%). The manipulation did not adversely affect TNC and MNC recoveries in either device. In addition, Optia achieved similar CD34+ cell recovery to that in large-BM-volume processing using the same device (147.5 vs. 184.5%, p = .112). During a follow-up period, neutrophil engraftment was achieved in all patients who received third-party RBC-manipulated grafts, and platelet engraftment was achieved in all cases, except one. CONCLUSION: The addition of third-party RBC to low RBC volume BM collections from or for pediatric patients does not have any negative impact on either RBC depletion or hematopoietic cell recovery during processing with the widely used cell separator.

DOI： 10.1111/trf.17039

Low hematocrit reduces the efficiency of CD34+ cell collection when using the Spectra Optia continuous mononuclear cell collection procedure. 国際誌

Takumi Kondo, Nobuharu Fujii, Keiko Fujii, Yuichi Sumii, Tomohiro Urata, Maiko Kimura, Masayuki Matsuda, Shuntaro Ikegawa, Kana Washio, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda

Transfusion 62 ( 5 ) 1065 - 1072 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: CD34+ cell collection efficiency (CE) is the determining factor when calculating processed blood volume (PBV) for leukapheresis (LP). However, the factors affecting CE in the continuous mononuclear cell collection (cMNC) protocol performed by the Spectra Optia apheresis system are not well established. STUDY DESIGN AND METHODS: We retrospectively collected the data from 147 consecutive apheresis procedures across 106 healthy donors and 27 patients completed between July 2016 and December 2020 at the Okayama University Hospital. All procedures were performed using the Optia cMNC protocol. RESULTS: The median CD34+ CE2 was significantly higher in the donor samples (64.3%) than in the patient samples (46.8%) (p < .0001). WBC counts, hematocrit, and platelet counts were all significantly higher in the donors than in the patients, and there was a moderate positive correlation between CD34+ CE2 and hematocrit (r = .47, p < .0001), with the equation of the line being y = 1.23x + 12.23. In contrast, there was only a very weak correlation between CD34+ CE2 and WBC or platelet count. In addition, low hematocrit correlated with an increased time to interface formation. CONCLUSION: These data revealed the negative impact of low hematocrit on the efficiency of CD34+ cell collection when using the Optia cMNC protocol and suggest that hematocrit values should also be considered when determining PBV.

DOI： 10.1111/trf.16856

Radiological evidence of resolution of fatty marrow after bone marrow transplantation. 国際誌

Kosuke Tamefusa, Motoharu Ochi, Kaori Fujiwara, Kana Washio

British journal of haematology 197 ( 4 ) 390 - 390 2022年5月

Registry data analysis of hematopoietic stem cell transplantation on systemic chronic active Epstein–Barr virus infection patients in Japan

Masahide Yamamoto, Maho Sato, Yasushi Onishi, Yoji Sasahara, Hideki Sano, Masayoshi Masuko, Hirohisa Nakamae, Ken‐ichi Matsuoka, Takahide Ara, Kana Washio, Makoto Onizuka, Kenichiro Watanabe, Yoshiyuki Takahashi, Tsuneaki Hirakawa, Miwako Nishio, Chizuko Sakashita, Tohru Kobayashi, Akihisa Sawada, Tatsuo Ichinohe, Takahiro Fukuda, Yoshiko Hashii, Yoshiko Atsuta, Ayako Arai

American Journal of Hematology 2022年3月

Late-onset familial Diamond-Blackfan anemia with neutropenia caused by RPL35A variant. 国際誌

Kosuke Tamefusa, Michiko Muraoka, Kana Washio, Manabu Wakamatsu, Akira Shimada

Pediatrics international : official journal of the Japan Pediatric Society 64 ( 1 ) e15275 2022年1月

Response to entrectinib in a malignant glioneuronal tumor with ARHGEF2-NTRK fusion. 国際誌

Kazuhiko Kurozumi, Kentaro Fujii, Kana Washio, Joji Ishida, Yoshihiro Otani, Tamotsu Sudo, Makoto Tahara, Koichi Ichimura, Daisuke Ennishi, Isao Date

Neuro-oncology advances 4 ( 1 ) vdac094 2022年

A survey of the support with education and jobs provided by hospitals for hematopoietic cell transplant survivors

Chihiro Kamoi, Hisakazu Nishimori, Kana Washio, Nobuharu Fujii, Yoshinobu Maeda

Japanese Journal of Transplantation and Cellular Therapy 11 ( 4 ) 199 - 205 2022年

Delayed Methotrexate Elimination after Administration of a Medium Dose of Methotrexate in a Patient with Genetic Variants Associated with Methotrexate Clearance.

Yasuhisa Tatebe, Kiichiro Kanamitsu, Hirotaka Kanzaki, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Yoshihisa Kitamura, Toshiaki Sendo, Akira Shimada, Hirokazu Tsukahara

Acta medica Okayama 74 ( 6 ) 545 - 550 2020年12月

記述言語：英語

Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner.

DOI： 10.18926/AMO/61215

Clinical Factors Affecting the Dose Conversion Ratio from Intravenous to Oral Tacrolimus Formulation among Pediatric Hematopoietic Stem Cell Transplantation Recipients. 国際誌

Kiichiro Kanamitsu, Takashi Yorifuji, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Akira Shimada, Hirokazu Tsukahara

Therapeutic drug monitoring 42 ( 6 ) 803 - 810 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Tacrolimus is converted from intravenous to oral formulation for the prophylaxis of graft-versus-host disease when patients can tolerate oral intake and graft-versus-host disease is under control. Oral tacrolimus formulation presents poor bioavailability with intraindividual and interindividual variations; however, some factors affecting its blood concentration among pediatric hematopoietic stem cell transplantation (HCT) recipients are still unclear. This study aimed to identify the clinical factors affecting tacrolimus blood concentrations after switching its formulation. METHODS: Changes in the blood concentration/dose ratio (C/D) of tacrolimus in pediatric HCT recipients were analyzed after the switching of tacrolimus from intravenous to oral formulation. Clinical records of 57 pediatric patients who underwent allogenic HCT from January 2006 to April 2019 in our institute were retrospectively reviewed. The C/D of tacrolimus before discontinuation of intravenous infusion (C/Div) was compared with the tacrolimus trough level within 10 days after the initiation of oral administration (C/Dpo). Multiple linear regression analysis was performed to identify factors affecting (C/Dpo)/(C/Div). RESULTS: The constant coefficient of (C/Dpo)/(C/Div) was 0.1692 [95% confidence interval (CI), 0.137-0.2011]. The concomitant use of voriconazole or itraconazole and female sex were significant variables with a beta coefficient of 0.0974 (95% CI, 0.062-0.133) and -0.0373 (95% CI, -0.072 to -0.002), respectively. CONCLUSIONS: After switching of tacrolimus formulation, pediatric HCT recipients might need oral tacrolimus dose that is 5-6 and 3.5-4.5 times the intravenous dose to maintain tacrolimus blood concentrations and area under the concentration-time curve, respectively. With the concomitant use of voriconazole or itraconazole, an oral tacrolimus dose of 4-5 times the intravenous dose seemed appropriate to maintain blood tacrolimus concentration.

DOI： 10.1097/FTD.0000000000000793

肝腫大によるoncologic emergencyを呈した神経芽腫の一例

尾山貴徳, 野田卓男, 谷守通, 納所洋, 谷本光隆, 石田悠志, 藤原かおり, 金光喜一郎, 鷲尾佳奈, 嶋田明

日本小児血液・がん学会雑誌 57 ( 3 ) 327 - 327 2020年11月

小児造血幹細胞移植患者において、タクロリムス経口製剤の生体利用率に影響を及ぼす因子に関する検討

金光喜一郎, 頼藤貴志, 石田悠志, 藤原かおり, 鷲尾佳奈, 嶋田明, 塚原宏一

日本小児血液・がん学会雑誌 57 ( 4 ) 327 - 327 2020年10月

Pediatric growing teratoma syndrome of the ovary: A case report and review of the literature. 国際誌

Takanori Oyama, Takuo Noda, Kana Washio, Akira Shimada

Medicine 99 ( 38 ) e22297 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

RATIONALE: Growing teratoma syndrome is defined as an increase in tumor size during or after systemic chemotherapy for germ cell tumors. These cases involve normal tumor maker levels and histological features of only mature teratoma. We report a rare case of an ovarian immature teratoma in a Japanese child that was diagnosed as growing teratoma syndrome. PATIENT CONCERNS: A 12-year-old girl presented a painful abdominal mass. She underwent left salpingo-oophorectomy for grade 1 immature teratoma in the left ovary. She did not undergo additional chemotherapy or radiotherapy. Four months later, she presented with grade 3 immature teratoma disseminated into the abdomen and pelvis. Chemotherapy resulted in the tumor maker levels returning to their normal ranges, although the tumors had grown slightly. DIAGNOSIS: The specimens resected by laparotomy after the chemotherapy consisted of mature tissue predominantly, although primitive neuroepithelium was observed in a small part of the specimen. The pathological diagnosis was grade 1 immature teratoma, notwithstanding the clinical diagnosis was growing teratoma syndrome based on the clinical features and pathogenesis. INTERVENTIONS: Laparotomy was performed at 7 months after the first operation, with resection of various tumors as well as the rectum, sigmoid colon, residual left fallopian duct, and a small part of the ileum and omentum. Some small tumors at the parietal peritoneum were ablated, although many tiny tumors around the uterus were left untreated. OUTCOMES: The patient has been free from recurrence for 5 years. LESSONS: Growing teratoma syndrome can develop in children, and their tumor size is comparable to that in adolescents and adults. Furthermore, development of growing teratoma syndrome from a primary germ cell tumor is presumably faster in children than in adolescents and adults. Complete resection of all growing teratoma tissue is recommended, although fertility-sparing surgery should be considered when possible.

DOI： 10.1097/MD.0000000000022297

A case of alveolar rhabdomyosarcoma showing concurrent responsive bone marrow lesions and refractory pancreatic lesions to pazopanib monotherapy. 国際誌

Kiichiro Kanamitsu, Hisashi Ishida, Kaori Fujiwara, Kana Washio, Akira Shimada, Hirokazu Tsukahara

Pediatric blood & cancer 67 ( 9 ) e28323 2020年9月

High-grade glioneuronal tumor with an ARHGEF2-NTRK1 fusion gene.

Kazuhiko Kurozumi, Yoshiko Nakano, Joji Ishida, Takehiro Tanaka, Masatomo Doi, Junko Hirato, Akihiko Yoshida, Kana Washio, Akira Shimada, Takashi Kohno, Koichi Ichimura, Hiroyuki Yanai, Isao Date

Brain tumor pathology 36 ( 3 ) 121 - 128 2019年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Here, we report a highly unusual case of high-grade glioneuronal tumor with a neurotrophic tropomyosin receptor kinase (NTRK) fusion gene. A 13-year-old girl presented with headache and vomiting and MRI detected two cystic lesions bilaterally in the frontal areas with surrounding edema. The left larger tumor was removed by left frontal craniotomy. The tumor was diagnosed as a high-grade glioneuronal tumor, unclassified. Methylation profiling classified it as a diffuse leptomeningeal glioneuronal tumor (DLGNT) with low confidence. This tumor showed genotypes frequently found in DLGNT such as 1p/19q codeletion without IDH mutation and, however, did not have the typical DLGNT clinical and histological features. RNA sequencing identified an ARHGEF2 (encoding Rho/Rac guanine nucleotide exchange factor 2)-NTRK1 fusion gene. The presence of recurrent NTRK fusion in glioneuronal tumors has an important implication in the clinical decision making and opens up a possibility of novel targeted therapy.

DOI： 10.1007/s10014-019-00345-y

High rates of ovarian function preservation after hematopoietic cell transplantation with melphalan-based reduced intensity conditioning for pediatric acute leukemia: an analysis from the Japan Association of Childhood Leukemia Study (JACLS).

Hisanori Fujino, Hiroyuki Ishida, Akihiro Iguchi, Masaei Onuma, Koji Kato, Mariko Shimizu, Masahiro Yasui, Hiroyuki Fujisaki, Kazuko Hamamoto, Kana Washio, Hirotoshi Sakaguchi, Emiko Miyashita, Yuko Osugi, Etsuko Nakagami-Yamaguchi, Akira Hayakawa, Atsushi Sato, Yoshiyuki Takahashi, Keizo Horibe

International journal of hematology 109 ( 5 ) 578 - 583 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Women are at high risk of hypergonadotropic hypogonadism after hematopoietic cell transplantation (HCT). Hypogonadism is universal after irradiation or busulfan. We hypothesized that reduced intensity conditioning (RIC) might protect ovarian function after HCT. We retrospectively reviewed data from patients with acute leukemia treated according to the Japan Association of Childhood Leukemia Study and nationwide multicenter study protocol. We selected 11 female patients with acute leukemia who received first HCT with RIC, had survived for three or more years after HCT, and were aged ≥ 12 years at the last follow-up visit. Median age at diagnosis, HCT, and last visit were 8, 10, and 17 years. Six patients received HLA-matched bone marrow (BM), two HLA-mismatched BM, and three cord blood. Melphalan was used as conditioning regimen in all patients. At the last visit, six of seven post-pubertal patients at transplantation recovered menstruation, and four of four patients who underwent transplantation at the pre-pubertal began menstruation. Height z scores showed no significant reduction between pre-transplant and post-transplant. No patients received growth hormone treatment. Only one recipient displayed subclinical hypothyroidism. Melphalan-based RIC may be an encouraging option for patients with acute leukemia to avoid ovarian and endocrine dysfunction after HCT.

DOI： 10.1007/s12185-019-02627-9

Panel-based next-generation sequencing identifies prognostic and actionable genes in childhood acute lymphoblastic leukemia and is suitable for clinical sequencing. 国際誌

Hisashi Ishida, Akihiro Iguchi, Michinori Aoe, Takahide Takahashi, Kosuke Tamefusa, Kiichiro Kanamitsu, Kaori Fujiwara, Kana Washio, Takehiro Matsubara, Hirokazu Tsukahara, Masashi Sanada, Akira Shimada

Annals of hematology 98 ( 3 ) 657 - 668 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although the cure rate of ALL has greatly improved, a considerable number of patients suffer from relapse of leukemia. Therefore, ALL remains the leading cause of death from cancer during childhood. To improve the cure rate of these patients, precisely detecting patients with high risk of relapse and incorporating new targeted therapies are urgently needed. This study investigated inexpensive, rapid, next-generation sequencing of more than 150 cancer-related genes for matched diagnostic, remission, and relapse samples of 17 patients (3 months to 15 years old) with relapsed ALL. In this analysis, we identified 16 single-nucleotide variants (SNVs) and insertion/deletion variants and 19 copy number variants (CNVs) at diagnosis and 28 SNVs and insertion/deletion variants and 22 CNVs at relapse. With these genetic alterations, we could detect several B cell precursor ALL patients with high-risk gene alterations who were not stratified into the highest-risk group (5/8, 62.5%). We also detected potentially actionable genetic variants in about half of the patients (8/17, 47.1%). Among them, we found that one patient harbored germline TP53 mutation as a secondary finding. This inexpensive, rapid method can be immediately applied as clinical sequencing and could lead to better management of these patients and potential improvement in the survival rate in childhood ALL.

DOI： 10.1007/s00277-018-3554-8

Remission of Congenital Multi-system Type Langerhans Cell Histiocytosis with Chemotherapy.

Kosuke Tamefusa, Hisashi Ishida, Kana Washio, Toshiaki Ishida, Hirosuke Morita, Akira Shimada

Acta medica Okayama 73 ( 1 ) 61 - 65 2019年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Patients with multi-system (MS)-type langerhans cell histiocytosis (LCH) show poor outcomes, especially congenital MS LCH cases were shown in high mortality rate. We experienced a congenital case of MS LCH with high risk organs, who needed intensive respiratory support after birth. Even though intensive chemotherapy was discontinued, this patient's lung LCH lesions gradually became reduced and his respiratory condition recovered; therefore, we restarted and completed maintenance chemotherapy. The patient maintained complete remission for more than 4 years after the end of chemotherapy. Our case suggests that congenital MS LCH even with severe organ involvement can be treated successfully with chemotherapy.

DOI： 10.18926/AMO/56459

Long-term Remission of Hepatitis-associated Aplastic Anemia Possibly due to Immunosuppressive Therapy after Liver Transplantation.

Kiichiro Kanamitsu, Kousuke Chayama, Kana Washio, Ryuichi Yoshida, Yuzo Umeda, Takahito Yagi, Akira Shimada

Acta medica Okayama 72 ( 5 ) 515 - 518 2018年10月

記述言語：英語

Hepatitis-associated aplastic anemia (HAAA) is an acquired bone marrow failure syndrome that develops after seronegative fulminant hepatitis. Abnormal cytotoxic T-cell activation with cytokine release is a possible pathophysiology. We present the case of a 16-month-old Japanese male who developed HAAA following living-donor liver transplantation for fulminant hepatitis. His aplastic anemia was successfully treated with immunosuppressive therapy. He had been administered tacrolimus for prophylaxis against hepatic allograft rejection. Ten years after the HAAA onset, the patient's bone marrow was found to be slightly hypoplastic. Tacrolimus may be effective in controlling abnormal immune reactions that can cause recurrent impaired hematopoiesis.

DOI： 10.18926/AMO/56250

Simultaneous detection of ABL1 mutation and IKZF1 deletion in Philadelphia chromosome-positive acute lymphoblastic leukemia using a customized target enrichment system panel

M. Aoe, H. Ishida, T. Matsubara, S. Karakawa, H. Kawaguchi, K. Fujiwara, K. Kanamitsu, K. Washio, K. Okada, M. Shibakura, A. Shimada

International Journal of Laboratory Hematology 40 ( 4 ) 427 - 436 2018年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Blackwell Publishing Ltd

Introduction: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary. Methods: We evaluated a next-generation sequencing (NGS)-based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNVs. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ALL patients. Results: Mono-allelic IKZF1 deletions were found in 4 patients at diagnosis. Furthermore, the mono-allelic deletions were found in exons of RB1, EBF1, PAX5 and ETV6 genes. Bi-allelic deletions were detected in CDKN2A and CDKN2B genes in 1 patient. ABL1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation-dependent probe amplification (MLPA) method or Sanger sequence. Conclusion: Next-generation sequencing-based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNVs in pediatric Ph+ALL simultaneously, and its results seem comparable with those of other methods.

DOI： 10.1111/ijlh.12805

多発肺転移を伴う甲状腺乳頭癌の自閉症児例

尾山貴徳, 野田卓男, 谷守通, 納所洋, 谷本光隆, 岩本貴行, 元木崇之, 樋口洋介, 藤原かおり, 石田悠志, 金光喜一郎, 鷲尾佳奈, 嶋田明

日本小児血液・がん学会雑誌 54 ( 3 ) 275 - 275 2017年12月

Sorafenib treatment for papillary thyroid carcinoma with diffuse lung metastases in a child with autism spectrum disorder: a case report. 国際誌

Yousuke Higuchi, Takayuki Motoki, Hisashi Ishida, Kiichiro Kanamitsu, Kana Washio, Takanori Oyama, Takuo Noda, Yasuko Tsurumaru, Ayumi Okada, Hirokazu Tsukahara, Akira Shimada

BMC cancer 17 ( 1 ) 775 - 775 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Pediatric papillary thyroid carcinoma frequently presents with lymph node involvement and distant metastases. Sorafenib, an oral multikinase inhibitor, has been used to treat radioactive iodine (RAI) therapy-refractory thyroid carcinoma in adults; however, pediatric experience is limited. Medical procedures and hospitalization for children with autism spectrum disorder may be challenging. CASE PRESENTATION: An 11-year-old boy with autism spectrum disorder and moderate intellectual impairment presented with dyspnea on exertion with thyroid carcinoma and diffuses lung metastases. Total thyroidectomy and adjuvant RAI therapy is the standard treatment; however, the latter therapy was impractical because of his respiratory status and challenging behaviors. He was therefore started on sorafenib 200 mg/day (150 mg/m2/day) and this dosage was increased to 400 mg/day (300 mg/m2/day). The adverse effects were mild and tolerable. After administration of medication, his dyspnea improved and surgery was performed. We attempted to administer RAI therapy after surgery; however, we abandoned it because he had difficulty taking care of himself according to isolation room rules. Thyrotropin suppression therapy was therefore started and sorafenib treatment (400 mg/day) resumed. Follow-up imaging showed regression of pulmonary metastases. The metastases have remained stable for over 24 months on continuous sorafenib treatment without serious adverse events. CONCLUSION: We inevitably used sorafenib as an alternative to standard therapy because of the patient's specific circumstances. Individualized strategies for pediatric cancer patients with autism spectrum disorder are needed.

DOI： 10.1186/s12885-017-3782-7

Gene expression analysis of hypersensitivity to mosquito bite, chronic active EBV infection and NK/T-lymphoma/leukemia. 国際誌

Kana Washio, Takashi Oka, Lamia Abdalkader, Michiko Muraoka, Akira Shimada, Megumi Oda, Hiaki Sato, Katsuyoshi Takata, Yoshitoyo Kagami, Norio Shimizu, Seiichi Kato, Hiroshi Kimura, Kazunori Nishizaki, Tadashi Yoshino, Hirokazu Tsukahara

Leukemia & lymphoma 58 ( 11 ) 2683 - 2694 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

The human herpes virus, Epstein-Barr virus (EBV), is a known oncogenic virus and plays important roles in life-threatening T/NK-cell lymphoproliferative disorders (T/NK-cell LPD) such as hypersensitivity to mosquito bite (HMB), chronic active EBV infection (CAEBV), and NK/T-cell lymphoma/leukemia. During the clinical courses of HMB and CAEBV, patients frequently develop malignant lymphomas and the diseases passively progress sequentially. In the present study, gene expression of CD16(-)CD56(+)-, EBV(+) HMB, CAEBV, NK-lymphoma, and NK-leukemia cell lines, which were established from patients, was analyzed using oligonucleotide microarrays and compared to that of CD56brightCD16dim/- NK cells from healthy donors. Principal components analysis showed that CAEBV and NK-lymphoma cells were relatively closely located, indicating that they had similar expression profiles. Unsupervised hierarchal clustering analyses of microarray data and gene ontology analysis revealed specific gene clusters and identified several candidate genes responsible for disease that can be used to discriminate each category of NK-LPD and NK-cell lymphoma/leukemia.

DOI： 10.1080/10428194.2017.1304762

多彩な合併症を呈するBeckwith-Wiedemann症候群に発症した乳児肝芽腫の一例

尾山貴徳, 野田卓男, 谷守通, 納所洋, 谷本光隆, 谷和祐, 石田悠志, 岡村朋香, 藤原かおり, 金光喜一郎, 鷲尾洋介, 鷲尾佳奈, 吉本順子, 嶋田明

日本小児血液・がん学会雑誌 54 ( 4 ) 333 - 333 2017年10月

A Case of Refractory Langerhans Cell Histiocytosis Complicated with Hemophagocytic Lymphohistiocytosis Rescued by Cord Blood Transplantation with Reduced-intensity Conditioning.

Kana Washio, Michiko Muraoka, Kiichiro Kanamitsu, Megumi Oda, Akira Shimada

Acta medica Okayama 71 ( 3 ) 249 - 254 2017年6月

記述言語：英語

We diagnosed a female infant with Langerhans cell histiocytosis (LCH) who was refractory to conventional chemotherapy. She showed refractory inflammation that was complicated with hemophagocytic lymphohistiocytosis (HLH) during LCH chemotherapy; therefore, we changed the protocol to HLH2004 (dexamethasone, cyclosporine A and VP16). However, there were no signs of hematological recovery. We therefore performed cord blood transplantation with reduced-intensity conditioning, and she achieved complete remission for over 2 years. As salvage therapy for refractory LCH, hematopoietic stem cell transplantation may be a good therapeutic choice, especially when LCH is complicated with HLH.

DOI： 10.18926/AMO/55208

Desmoid-type fibromatosis in a boy with Down syndrome. 国際誌

Hisashi Ishida, Kousuke Chayama, Kiichiro Kanamitsu, Kana Washio, Takehiro Tanaka, Akira Shimada

Pediatrics international : official journal of the Japan Pediatric Society 59 ( 5 ) 624 - 626 2017年5月

記述言語：英語

Patients with Down syndrome (DS) have a markedly higher incidence of childhood leukemia, but a lower incidence of most solid tumors, compared with age-matched euploid individuals. Trisomy 21 might be protective against tumorigenesis because of several tumor suppressive mechanisms. Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterized by a variable clinical course. In recent reports, almost all cases of DF involved genomic alterations associated with activation of the Wnt/β-catenin pathway. Here, we report the case of a boy with DS who developed DF without activation of the Wnt/β-catenin pathway. To the best of our knowledge, this is the first case of DS involving DF.

DOI： 10.1111/ped.13241

[Prognostic Impact of Radiation Therapy and Molecular Classification of Infant Atypical Teratoid/Rhabdoid Tumors].

Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Takao Yasuhara, Kana Washio, Akira Shimada, Norihisa Katayama, Kuniaki Katsui, Hiroyuki Yanai, Isao Date

No shinkei geka. Neurological surgery 45 ( 2 ) 147 - 154 2017年2月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Atypical teratoid/rhabdoid tumor(AT/RT)is a rare and lethal childhood cancer. Although radiation therapy in children less than three years of age is generally deferred because of its neural toxicity, recent studies have shown that multimodal therapies, including radiation therapy, are effective in pediatric patients with AT/RT less than three years of age. We treated four infant AT/RT patients and investigated the impact of radiation therapy and genetic classification on the prognosis. The mean age at the time of the operation was 9.3 months and all patients were female. All patients underwent surgical resection. Of the four patients, two received combined irradiation and chemotherapy. Specifically, one patient received conformal craniospinal radiation therapy and the other received craniospinal irradiation with proton beams. Immunohistochemical analyses of tumor specimens revealed that the two patients were positive for ASCL1, a regulator of Notch signaling. Patients who received radiation therapy and exhibited ASCL1-positive tumors had a better prognosis. We conclude that radiation therapy may prolong survival in AT/RT patients who are less than 3 years of age. However, further study is required to evaluate long-term functional outcomes.

DOI： 10.11477/mf.1436203466

Two Relapsed Stage III Childhood Anaplastic Large Cell Lymphoma Patients with NPM-ALK Fusion in Bone Marrow from Initial Diagnosis.

Yui Kanazawa, Yuka Yamashita, Mitsuhiro Fujiwara, Michiko Muraoka, Kana Washio, Kiichiro Kanamitsu, Hisashi Ishida, Takae Nakano, Miho Yamada, Keizo Horibe, Takehiro Tanaka, Tadashi Yoshino, Akira Shimada

Acta medica Okayama 70 ( 6 ) 503 - 506 2016年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Childhood anaplastic large cell lymphoma (ALCL) accounts for approx. 10-30% of cases of non-Hodgkin lymphoma, and the ALCL99 study reported 60-75 disease-free survival; however, a relatively high relapse rate was observed (25-30% ). We report 2 patients with Stage III ALCL who relapsed 6-18 months after the end of ALCL99 chemotherapy. A retrospective molecular analysis identified the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion gene in the first diagnostic bone marrow samples taken from both patients. However, antibodies against the ALK protein appeared to be relatively low in the serum of both patients (×100 and ×750). An increase in chemotherapy intensity may be beneficial if Stage III ALCL patients are shown to be NPM-ALK chimera-positive in the first diagnostic bone marrow sample.

化学療法を行った先天性全身型黄色肉芽腫症の一例(A case of congenital systemic juvenile xanthogranuloma treated with chemotherapy)

金光喜一郎, 石田悠志, 藤原かおり, 鷲尾佳奈, 田中健大, 嶋田明

日本小児血液・がん学会雑誌 53 ( 4 ) 245 - 245 2016年11月

Relapsed infant MLL-rearranged acute lymphoblastic leukemia with additional genetic alterations. 国際誌

Hisashi Ishida, Kiichiro Kanamitsu, Kana Washio, Michiko Muraoka, Kanae Sakakibara, Takehiro Matsubara, Hirotaka Kanzaki, Akira Shimada

Pediatric blood & cancer 63 ( 11 ) 2059 - 60 2016年11月

MIBG陰性神経芽腫に対するFDG-PETの有用性(Value of FDG-PET for the assessment of treatment efficacy in MIBG-negative neuroblastoma patients)

尾山貴徳, 野田卓男, 谷守通, 納所洋, 谷本光隆, 藤原かおり, 石田悠志, 金光喜一郎, 鷲尾佳奈, 嶋田明

日本小児血液・がん学会雑誌 53 ( 4 ) 231 - 231 2016年11月

Adults with germline CBL mutation complicated with juvenile myelomonocytic leukemia at infancy. 国際誌

Michiko Muraoka, Chiho Okuma, Kiichiro Kanamitsu, Hisashi Ishida, Yui Kanazawa, Kana Washio, Masafumi Seki, Motohiro Kato, Junko Takita, Yusuke Sato, Seishi Ogawa, Hirokazu Tsukahara, Megumi Oda, Akira Shimada

Journal of human genetics 61 ( 6 ) 523 - 6 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Juvenile myelomonocytic leukemia (JMML) appears to be a life-threatening disease and showed poor prognosis even after hematopoietic stem cell transplantation (HSCT) because of high relapse rate. On the other hand, recent molecular analysis revealed the heterogeneity of JMML. Here we report that two JMML patients survived >20 years without HSCT and both patients had uniparental disomy of 11q23 where CBL is located without the phenomenon found in neither Noonan syndrome nor Noonan syndrome-like disorder. We think that some JMML patients with CBL mutation might show the good prognosis in later life after remission of JMML.

DOI： 10.1038/jhg.2016.8

Persistent clonal chromosomal abnormalities in a chronic myeloid leukemia patient. 国際誌

Michiko Muraoka, Kana Washio, Kiichiro Kanamitu, Yui Kanazawa, Toshiaki Ishida, Takako Miyamura, Kosuke Chayama, Ritsuo Nishiuchi, Megumi Oda, Akira Shimada

Pediatrics international : official journal of the Japan Pediatric Society 58 ( 1 ) 53 - 6 2016年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Clonal cytogenetic abnormalities (CCA) in Philadelphia chromosome (Ph)-negative cells have been reported in a small population of adult chronic myelogenous leukemia (CML) patients during the clinical course, but CCA in pediatric CML patients are rarely reported. We herein report the case of an 8-year-old boy from the onset of CML. Although he had relapse after unrelated bone marrow transplantation when 9 years old, he has since been in complete molecular response on imatinib mesylate treatment. Surprisingly, various CCA have been observed in this patient, including several reciprocal chromosomal translocations in Ph-negative cells for >12 years. Although dysplasia in the bone marrow cells was identified, no overt transformation to myelodysplastic syndrome or acute myeloid leukemia has been observed. The cause of the CCA remains unknown in this patient, and careful observation is required.

DOI： 10.1111/ped.12739

A Long-term Survivor after Congenital Acute Myeloid Leukemia with t(8 ; 16)(p11 ; p13).

Takae Hanada, Kiichiro Kanamitsu, Kosuke Chayama, Takako Miyamura, Yui Kanazawa, Michiko Muraoka, Kana Washio, Masahide Imada, Misao Kageyama, Akihito Takeuchi, Kei Tamai, Megumi Oda, Akira Shimada

Acta medica Okayama 70 ( 1 ) 31 - 5 2016年

記述言語：英語掲載種別：研究論文（学術雑誌）

The treatment of patients with congenital leukemia is difficult and often results in a poor prognosis. We present here the case of a female child with congenital acute myeloid leukemia (AML) with t(8 ; 16) (p11 ; p13) who received chemotherapy and survived for more than 10 years without relapse. A novel MOZ-CBP chimera was found in her diagnostic sample. Although adult AML patients with MOZ-CBP have mainly been reported as having therapy-related AML and showed poor prognoses, the present case supports the idea that AML with MOZ-CBP in the pediatric population might show better prognoses.

頸部異所性胸腺と縦隔内胸腺に同時発生したLangerhans cell histiocytosisの1例

納所洋, 野田卓夫, 尾山貴徳, 谷本光隆, 金光喜一郎, 鷲尾佳奈, 嶋田明, 小田慈

日本小児血液・がん学会雑誌 52 ( 3 ) 339 - 339 2015年10月

先天性角化不全症に合併した多発肝転移を伴う横行結腸癌の1例

尾山貴徳, 野田卓男, 納所洋, 谷本光隆, 金光喜一郎, 鷲尾佳奈, 嶋田明, 小田慈, 神崎洋光, 永坂岳司

日本小児血液・がん学会雑誌 52 ( 3 ) 340 - 340 2015年10月

胎生期早期の発生が疑われたランゲルハンス組織球症の1例(Suspected early onset of congenital Langerhans cell histiocytosis involving ectopic cervical thymus and mediastinal thymus, simultaneously)

金光喜一郎, 石田悠志, 鷲尾佳奈, 小田慈, 野田卓男, 尾山貴徳, 谷本光隆, 田中健大, 井田健太郎, 嶋田明

日本小児血液・がん学会雑誌 52 ( 4 ) 236 - 236 2015年10月

小児固形腫瘍におけるFDG-PET/CTの有用性の検討(Usefulness of FDG-PET/CT for pediatric solid tumor)

納所洋, 野田卓男, 尾山貴徳, 谷本光隆, 嶋田明, 鷲尾佳奈, 金光喜一郎, 石田悠志

日本小児血液・がん学会雑誌 52 ( 4 ) 336 - 336 2015年10月

免疫異常骨髄異形成症候群と大腸多発癌を合併した先天性角化不全症の1例(Immune disorder A case of dyskeratosis congenita developed myelodysplastic syndrome and multiple colon cancer)

尾山貴徳, 野田卓男, 納所洋, 谷本光隆, 石田悠志, 金光喜一郎, 鷲尾佳奈, 長谷川高誠, 田中弘之, 神崎洋光, 永坂岳司, 嶋田明

日本小児血液・がん学会雑誌 52 ( 4 ) 214 - 214 2015年10月

甲状腺乳頭がん・多発肺転移に対してsorafenibを用いた自閉症スペクトラムの11歳男児の1例(Using sorafenib in pediatric patient with papillary thyroid carcinoma with diffuse lung metastases: A case of 11-years-old boy with autism)

樋口洋介, 石田悠志, 金光喜一郎, 鷲尾佳奈, 嶋田明, 野田卓男, 尾山貴徳, 元木崇之

日本小児血液・がん学会雑誌 52 ( 4 ) 376 - 376 2015年10月

Suspected early onset of congenital Langerhans cell histiocytosis involving ectopic cervical thymus and mediastinal thymus, simultaneously. 国際誌

Kiichiro Kanamitsu, Kana Washio, Megumi Oda, Takuo Noda, Takanori Oyama, Terutaka Tanimoto, Takehiro Tanaka, Kentaro Ida, Akira Shimada

Pediatric blood & cancer 62 ( 8 ) 1491 - 2 2015年8月

ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases.

Michinori Aoe, Akira Shimada, Michiko Muraoka, Kana Washio, Yoshimi Nakamura, Takahide Takahashi, Masahide Imada, Toshiyuki Watanabe, Ken Okada, Ritsuo Nishiuchi, Takako Miyamura, Kosuke Chayama, Misako Shibakura, Megumi Oda, Tsuneo Morishima

International journal of hematology 99 ( 5 ) 609 - 15 2014年

記述言語：英語掲載種別：研究論文（学術雑誌）

The tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) revolutionized the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL), which had showed poor prognosis before the dawn of IM treatment. However, if Ph-ALL patients showed IM resistance due to ABL kinase mutation, second-generation TKI, dasatinib or nilotinib, was recommended. We treated 4 pediatric Ph-ALL patients with both IM and bone marrow transplantation (BMT); however, 3 relapsed. We retrospectively examined the existence of ABL kinase mutation using PCR and direct sequencing methods, but there was no such mutation in all 4 diagnostic samples. Interestingly, two relapsed samples from patients who were not treated with IM before relapse did not show ABL kinase mutation and IM was still effective even after relapse. On the other hand, one patient who showed resistance to 3 TKI acquired dual ABL kinase mutations, F359C at the IM-resistant phase and F317I at the dasatinib-resistant phase, simultaneously. In summary, Ph-ALL patients relapsed with or without ABL kinase mutation. Furthermore, ABL kinase mutation was only found after IM treatment, so an IM-resistant clone might have been selected during the IM treatment and intensive chemotherapy. The appropriate combination of TKI and BMT must be discussed to cure Ph-ALL patients.

DOI： 10.1007/s12185-014-1565-3

Activation of Akt is associated with poor prognosis and chemotherapeutic resistance in pediatric B-precursor acute lymphoblastic leukemia. 国際誌

Naoto Morishita, Hirokazu Tsukahara, Kosuke Chayama, Toshiaki Ishida, Kana Washio, Takako Miyamura, Nobuko Yamashita, Megumi Oda, Tsuneo Morishima

Pediatric blood & cancer 59 ( 1 ) 83 - 9 2012年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, a pro-survival pathway, plays important roles in tumor cell growth. However, the role of Akt in the pathogenesis of pediatric B-precursor acute lymphoblastic leukemia (B-pre ALL) remains to be clarified. This study was undertaken to explore the clinical relevance and molecular mechanisms underlying the activation of Akt (i.e., phosphorylated Akt, P-Akt) in pediatric B-pre ALL. PROCEDURE: We evaluated the activation status of Akt in bone marrow samples from 21 children with newly diagnosed B-pre ALL and correlated the expression level of P-Akt with clinicopathologic and prognostic features. Additionally, we transfected the myristoylated Akt cDNA into the B-pre ALL cell line, Nalm-6, and examined the effect, in vitro, of Akt activation on the response to antitumor drugs. RESULTS: P-Akt expression in B-pre ALL blast cells at diagnosis was associated significantly with poor response to induction chemotherapy including prednisolone, dexamethasone, vincristine, and adriamycin in B-pre ALL patients. Both overall survival and relapse-free survival in patients with P-Akt expression were reduced significantly more than in patients without P-Akt expression. Activation of Akt reduced the extent of apoptosis induced by the antitumor drugs in Nalm-6 listed above. Activation of Akt did not induce expression of P-glycoprotein, a drug transporter that is capable of conferring multidrug resistance. CONCLUSION: These results support the contention that Akt activation is a mechanism of chemotherapeutic resistance in B-pre ALL and suggest that Akt can be a therapeutic target for the treatment of relapsed or refractory pediatric B-pre ALL.

DOI： 10.1002/pbc.24034

Successful treatment of unresectable advanced hepatoblastoma: living liver transplantation after surgical removal of lung metastasis. 国際誌

Takako Miyamura, Ryuichi Yoshida, Takahito Yagi, Hiroyoshi Matsukawa, Kousuke Chayama, Toshiaki Ishida, Kana Washio, Naoto Morishita, Megumi Oda, Tsuneo Morishima

Pediatric transplantation 15 ( 5 ) E87-91 2011年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Hepatoblastoma is a rare malignant tumor of the liver in children. Intensive combination chemotherapy has increased the number of surgically resectable cases and improved prognosis markedly. However, unresectable cases and cases with residual metastasis, including lung metastases, have a poor prognosis. In these refractory cases, treatment strategy has not been established. On the other hand, living liver transplantation has been shown to be effective in cases of advanced hepatoblastoma, but its effectiveness in cases with residual distant metastases after chemotherapy remains unclear. We report one successful case of advanced unresectable hepatoblastoma with multiple lung metastases. Intensive chemotherapy consisting of high-dose chemotherapy with autologous hematopoietic stem cell transplantation was not effective. We performed living liver transplantation after surgical resection of residual lung metastases, which were histologically viable. After liver transplantation, the level of tumor marker decreased gradually. The patient experienced no severe complications. This case suggested that living liver transplantation could be effective in cases of advanced refractory hepatoblastoma after control of distant metastases.

DOI： 10.1111/j.1399-3046.2009.01262.x

Cumulative kinetics of epigenetic abnormalities during initiation and progression of Adult T-cell Leukemia/Lymphoma (ATLL).

Oka T, Sato H, Al-Kader LA, Shinnou Y, Washio K, Takata K, Murakami I, Utsunomiya A, Ouchida M, Takahashi K, Yoshino T

Retrovirology 2011年6月

Multi-step aberrant CpG island hyper-methylation is associated with the progression of adult T-cell leukemia/lymphoma. 国際誌

Hiaki Sato, Takashi Oka, Yoko Shinnou, Takami Kondo, Kana Washio, Masayuki Takano, Katsuyoshi Takata, Toshiaki Morito, Xingang Huang, Maiko Tamura, Yuta Kitamura, Nobuya Ohara, Mamoru Ouchida, Koichi Ohshima, Kenji Shimizu, Mitsune Tanimoto, Kiyoshi Takahashi, Masao Matsuoka, Atae Utsunomiya, Tadashi Yoshino

The American journal of pathology 176 ( 1 ) 402 - 15 2010年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Aberrant CpG island methylation contributes to the pathogenesis of various malignancies. However, little is known about the association of epigenetic abnormalities with multistep tumorigenic events in adult T cell leukemia/lymphoma (ATLL). To determine whether epigenetic abnormalities induce the progression of ATLL, we analyzed the methylation profiles of the SHP1, p15, p16, p73, HCAD, DAPK, hMLH-1, and MGMT genes by methylation specific PCR assay in 65 cases with ATLL patients. The number of CpG island methylated genes increased with disease progression and aberrant hypermethylation in specific genes was detected even in HTLV-1 carriers and correlated with progression to ATLL. The CpG island methylator phenotype (CIMP) was observed most frequently in lymphoma type ATLL and was also closely associated with the progression and crisis of ATLL. The high number of methylated genes and increase of CIMP incidence were shown to be unfavorable prognostic factors and correlated with a shorter overall survival by Kaplan-Meyer analysis. The present findings strongly suggest that the multistep accumulation of aberrant CpG methylation in specific target genes and the presence of CIMP are deeply involved in the crisis, progression, and prognosis of ATLL, as well as indicate the value of CpG methylation and CIMP for new diagnostic and prognostic biomarkers.

DOI： 10.2353/ajpath.2010.090236

Multi-step accumulation of aberrant CpG island hypermethylation during progression of lymphoma/leukemia

Takashi Oka, Takami Kondo, Hiaki Sato, Yoko Nakatani, Kana Washio, Ichiro Murakami, Nobuya Ohara, Kiyoshi Takahashi, Mamoru Ouchida, Mitsune Tanimoto, Tadashi Yoshino

International Journal of Molecular Medicine 26 ( Sup1 ) S44 - S44 2010年

IMMUNOHISTOCHEMICAL ANALYSES OF PTPN6 (SHP1) IN LANGERHANS CELL HISTIOCYTOSIS 査読

Ichiro Murakami, Takashi Oka, Hiaki Sato, Toshiaki Morito, Katsuyoshi Takata, Yoko Shinno, Masayuki Takano, Kana Washio, Shingo Ko, Maiko Tamura, Naoko Ohnishi, Koichi Ichimura, Yasuharu Sato, Hiroyuki Yanai, Nobuya Ohara, Eisaku Kondo, Kiyoshi Takahashi, Takehiro Tanaka, Jean Gogusev, Francis Jaubert, Akira Morimoto, Shinsaku Imashuku, Tadaatsu Akagi, Tadashi Yoshino

PEDIATRIC BLOOD & CANCER 53 ( 4 ) 691 - 691 2009年10月

Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma. 国際誌

Takami Kondo, Takashi Oka, Hiaki Sato, Yoko Shinnou, Kana Washio, Masayuki Takano, Toshiaki Morito, Katsuyoshi Takata, Nobuya Ohara, Mamoru Ouchida, Kenji Shimizu, Tadashi Yoshino

International journal of oncology 35 ( 3 ) 547 - 57 2009年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Aberrant DNA hypermethylation is an important mechanism for the inactivation of tumor-related genes in human tumors. Gastric mucosa-associated lymphoid tissue (MALT) lymphomas arise from Helicobacter pylori-associated chronic gastritis; most patients are H. pylori-positive and eradication therapy is highly effective. In the present study, we used methylation-specific PCR to analyze the DNA methylation status of 11 tumor-related genes (Kip2, p16, hMLH-1, p15, p73, MGMT, DAPK, MINT1, MINT2, MINT31 and HCAD) in 21 specimens of MALT lymphoma, 5 specimens of MALT lymphoma with large cell component (high-grade MALT lymphoma), 15 specimens of diffuse large B-cell lymphoma (DLBCL), 8 specimens of complete remission of MALT lymphoma after eradication therapy, 5 specimens with no evidence of malignancy and PBMCs from 10 healthy donors. The average number of methylated genes was significantly greater in gastric lymphomas as compared to normal controls (P<0.001). The CpG island methylator phenotype (CIMP) was observed in 93.3% (14/15) of DLBCLs, 100% (5/5) of high-grade MALT lymphomas and 61.9% (13/21) of MALT lymphomas; in contrast, CIMP was not found in the control group (0%). The average number of methylated genes and the CIMP incidence significantly increased with H. pylori infection. Furthermore, aberrant CpG methylation of specific genes, such as p16, MGMT and MINT31, was consistently associated with H. pylori infection. These findings strongly suggest that H. pylori infection causes the aberrant DNA hypermethylation of specific genes and induces CIMP, which is an important epigenetic mechanism for the development and progression of gastric MALT lymphoma; additionally, our findings provide new epigenetic markers.

Two cases of chronic active Epstein-Barr virus infection in which EBV-specific cytotoxic T lymphocyte was induced after allogeneic bone marrow transplantation. 国際誌

Takako Miyamura, Kousuke Chayama, Tomoaki Wada, Kazunari Yamaguchi, Nobuko Yamashita, Toshiaki Ishida, Kana Washio, Naoto Morishita, Akira Manki, Megumi Oda, Tsuneo Morishima

Pediatric transplantation 12 ( 5 ) 588 - 92 2008年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

CAEBV is a high mortality and morbidity disease with life-threatening complications. Nevertheless, the treatment regimens for CAEBV have not yet been established. Although some reports have described CAEBV therapy involving treatments such as antiviral drugs, immunomodulatory agents, and immunochemotherapy, none of these treatments have been demonstrated to be effective. The only treatment reported to be effective is allogeneic SCT. However, the complications of SCT are severe, so treatment results have been poor. Recently, immunotherapy has been devised, but this is still in the developmental stage. In this report, two cases of CAEBV in which allogeneic SCT was performed soon after diagnosis are reported. In both cases, a high EBV genome titer in the peripheral blood was detected at onset. After SCT, the EBV genome titer decreased as CTL activity gradually increased. This fact suggested that not only high-dose chemotherapy as a preconditioning treatment of SCT but also increased CTL activity which could eliminate virus-infected cells might be effective, although additional cases should be studied in order to establish effective treatments.

DOI： 10.1111/j.1399-3046.2007.00873.x

Longitudinal analysis of Epstein-Barr virus-associated illness. 国際誌

Nobuko Yamashita, Kosuke Chayama, Takako Miyamura, Tomoaki Wada, Hidehiko Maruyama, Kana Washio, Takayuki Miyai, Tsuneo Morishima

Pediatrics international : official journal of the Japan Pediatric Society 50 ( 3 ) 388 - 91 2008年6月

Epigenetically distinct malignant cell population forms lymphoma-involving lesions in acute type adult T cell Leukemia/Lymphoma (ATLL)

Takashi Oka, Hiaki Sato, Yoko Nakatani, Takami Kondo, Kana Washio, Masayuki Takano, Ichiro Murakami, Nobuya Ohara, Mamoru Ouchida, Koichi Ohshima, Kenji Shimizu, Mitsune Tanimoto, Kiyoshi Takahashi, Atae Utsunomiya, Tadashi Yoshino

AIDS RESEARCH AND HUMAN RETROVIRUSES 23 ( 4 ) 627 - 628 2007年4月

Molecular pathological analysis of the protein tyrosine phosphatase: SHP1 gene in the pathogenesis of lymphoma and leukemias

Takashi Oka, Yoko Nakatani, Takami Kondo, Hiaki Sato, Kana Washio, Masayuki Takano, Ichirou Murakami, Yuriko Nishikawa, Mamoru Ouchida, Nobuya Ohara, Kiyoshi Takahashi, Kazuhiko Hayashi, Mitsune Tanimoto, Kenji Shimizu, Tadashi Yoshino

CANCER RESEARCH 66 ( 8 ) 2006年4月

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