Faculty Profiles - TAKAHASHI, Yoshiyuki

Lower limb pain following allogeneic hematopoietic stem cell transplantation in Japanese children. Reviewed

Kenichi Mishima, Hiroshi Kitoh, Masaki Matsushita, Tadashi Nagata, Yasunari Kamiya, Yoshiyuki Takahashi, Naoki Ishiguro

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association Vol. 25 ( 4 ) page： 682 - 687 2020.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) can experience musculoskeletal pains in their lower limbs in the early and late post-transplantation period. This study investigated demographics and clinical characteristics of the lower limb pain (LLP) among Japanese survivors of pediatric allo-HSCT. METHODS: A total of 143 consecutive Japanese patients who had undergone allo-HSCT less than 18 years of age in a single institute between 2005 and 2015 were reviewed. Patients referred for in-house orthopedic evaluation of their sustained LLPs that impaired ambulation were defined as LLP group. Illness/transplantation-related parameters were compared between LLP group and non-LLP group. RESULTS: Ninety children with a mean age of 8.5 years at transplantation were enrolled. Their median follow-up period following transplantation was 6.3 years (range, 2.1-12.5). There were four patients in LLP group, whose etiologies were AVN of the femoral head and insufficiency fracture (ISF) of the tibia or the medial cuneiform bone. Cumulative dose of steroids that administered from six months before transplantation to six months after discharge from hospitalization for transplantation was significantly higher in LLP group than non-LLP group. Additionally, the two groups differed significantly in terms of hospitalization period after transplantation. LLP caused by AVN of the femoral head manifested between six months and two years, whereas that caused by ISF within the first six months after transplantation. CONCLUSIONS: The incidence of sustained LLP that impairs ambulation following contemporary allo-HSCT is not common in Japanese pediatric survivors. The risk of developing musculoskeletal LLP may increase with a higher steroid dosage in the peri-transplant period. LLP caused by AVN of the femoral head is likely to manifest later than that caused by ISF.

DOI： 10.1016/j.jos.2019.07.007

Conditioning regimen for allogeneic bone marrow transplantation in children with acquired bone marrow failure: fludarabine/melphalan vs. fludarabine/cyclophosphamide. Reviewed International journal

Nao Yoshida, Yoshiyuki Takahashi, Hiromasa Yabe, Ryoji Kobayashi, Kenichiro Watanabe, Kazuko Kudo, Miharu Yabe, Takako Miyamura, Katsuyoshi Koh, Hiroshi Kawaguchi, Hiroaki Goto, Naoto Fujita, Keiko Okada, Yasuhiro Okamoto, Koji Kato, Masami Inoue, Ritsuro Suzuki, Yoshiko Atsuta, Seiji Kojima

Bone marrow transplantation Vol. 55 ( 7 ) page： 1272 - 1281 2020.7

Language：English Publishing type：Research paper (scientific journal)

Fludarabine/cyclophosphamide-based conditioning regimens are standard in bone marrow transplantation (BMT) for acquired bone marrow failure in children, however, graft failure may occur. Using the data from a nationwide transplantation registry, we compared the outcomes of children aged <16 years with acquired aplastic anemia and refractory cytopenia of childhood who underwent allogeneic BMT with either fludarabine/melphalan (n = 71) or fludarabine/cyclophosphamide (n = 296) between 2000 and 2016. The fludarabine/melphalan regimen provided excellent outcomes, with 3-year overall survival and failure-free survival rates of 98% and 97%, respectively. The 83% 3-year failure-free survival in the fludarabine/cyclophosphamide group was significantly inferior (P = 0.002), whereas the overall survival did not differ between the two groups. Late graft failure was the most common cause of treatment failure in the fludarabine/cyclophosphamide group, which experienced a significantly higher incidence of late graft failure than the fludarabine/melphalan group (11% vs. 3%; P = 0.035). Multivariate analyses showed that the fludarabine/melphalan regimen was associated with a better failure-free survival (hazard ratio [HR] 0.12; P = 0.005) and lower risk of late graft failure (HR 0.16; P = 0.037). Fludarabine/melphalan-based conditioning regimen can be a promising option for children with acquired bone marrow failure receiving BMT.

DOI： 10.1038/s41409-020-0948-8

Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia

Tsuzuki, S; Yasuda, T; Kojima, S; Kawazu, M; Akahane, K; Inukai, T; Imaizumi, M; Morishita, T; Miyamura, K; Ueno, T; Karnan, S; Ota, A; Hyodo, T; Konishi, H; Sanada, M; Nagai, H; Horibe, K; Tomita, A; Suzuki, K; Muramatsu, H; Takahashi, Y; Miyazaki, Y; Matsumura, I; Kiyoi, H; Hosokawa, Y; Mano, H; Hayakawa, F

BLOOD CANCER DISCOVERY Vol. 1 ( 1 ) page： 82 - 95 2020.7

Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia Reviewed

Shinobu Tsuzuki, Takahiko Yasuda, Shinya Kojima, Masahito Kawazu, Koshi Akahane, Takeshi Inukai, Masue Imaizumi, Takanobu Morishita, Koichi Miyamura, Toshihide Ueno, Sivasundaram Karnan, Akinobu Ota, Toshinori Hyodo, Hiroyuki Konishi, Masashi Sanada, Hirokazu Nagai, Keizo Horibe, Akihiro Tomita, Kyogo Suzuki, Hideki Muramatsu, Yoshiyuki Takahashi, Yasushi Miyazaki, Itaru Matsumura, Hitoshi Kiyoi, Yoshitaka Hosokawa, Hiroyuki Mano, Fumihiko Hayakawa

Blood Cancer Discovery Vol. 1 ( 1 ) page： 82 - 95 2020.7

【骨髄不全症の病態と検査】骨髄不全症と遺伝子異常血球テロメア長測定の臨床的意義

成田敦, 高橋義行

臨床検査 Vol. 64 ( 7 ) page： 761 - 765 2020.7

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(株)医学書院

＜文献概要＞Point ●再生不良性貧血(AA)を含む骨髄不全症患者ではテロメア長の短縮がみられる.造血ストレスに伴う二次性の変化が原因と考えられている.●骨髄不全症患者の一部にはテロメラーゼ複合体遺伝子群の変異を有する患者がいる.診断補助としてテロメア長の測定が有用である.●特徴的な身体症状がみられない不全型の先天性角化不全症(DC)においてはテロメア長の測定や遺伝子診断が必須である.

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01541&link_issn=&doc_id=20200714070008&doc_link_id=10.11477%2Fmf.1542202408&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1542202408&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Safe diagnostic management of malignant mediastinal tumors in the presence of respiratory distress: a 10-year experience. Reviewed International journal Open Access

Tomoko Tanaka, Hizuru Amano, Yujiro Tanaka, Yoshiyuki Takahashi, Tatsuro Tajiri, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Kazuki Yokota, Satoshi Makita, Yukiko Tani, Akinari Hinoki, Hiroo Uchida

BMC pediatrics Vol. 20 ( 1 ) page： 292 - 292 2020.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The fundamental treatment for patients with pediatric malignant mediastinal tumors is chemotherapy. Therefore, accurate diagnosis is essential for selecting the appropriate chemotherapeutic regimen. However, malignant mediastinal tumors occasionally cause respiratory distress, and biopsies under general anesthesia are dangerous for such patients as invasive mechanical ventilation can aggravate airway obstruction caused by mass effect. In this study, we reviewed our 10-year diagnostic experience to evaluate the efficacy of our practices and confirm a safe diagnostic protocol for future patients. METHODS: We retrospectively reviewed medical records of children with malignant mediastinal tumors diagnosed at Nagoya University Hospital from 2007 to 2018 who demonstrated respiratory distress. Respiratory distress included dyspnea, massive pleural effusion, wheezing, and hypoxemia owing to tumors. Data on sex, age at onset, primary symptoms, location of tumor, management strategy (especially the method of diagnosis and definitive diagnosis), clinical course, prognosis during the acute phase (within 3 months from the onset of respiratory symptoms), and long-term outcome were collected. RESULTS: Twelve pediatric patients met the review criteria. There were seven anterior mediastinal tumors and five posterior mediastinal tumors. All anterior mediastinal tumors were diagnosed via bone marrow smear, thoracentesis, or core needle biopsy while maintaining spontaneous breathing. Regarding posterior tumors, two patients were diagnosed via a core needle biopsy and lymph node excisional biopsy under spontaneous breathing. Two cases were initially diagnosed solely using tumor markers. One patient with severe tracheal compression underwent tumor resection with extracorporeal membrane oxygenation stand-by. No patient died of diagnostic procedure-related complications. CONCLUSIONS: In 11 of the 12 cases reviewed, safe and accurate tumor diagnosis was accomplished without general anesthesia. A diagnostic strategy without general anesthesia considering the tumor location proved to be useful.

DOI： 10.1186/s12887-020-02183-w

Impact of graft-versus-host disease on the clinical outcome of allogeneic hematopoietic stem cell transplantation for non-malignant diseases. Reviewed

Katsutsugu Umeda, Kohsuke Imai, Masakatsu Yanagimachi, Hiromasa Yabe, Masao Kobayashi, Yoshiyuki Takahashi, Michiko Kajiwara, Nao Yoshida, Yuko Cho, Masami Inoue, Yoshiko Hashii, Yoshiko Atsuta, Tomohiro Morio

International journal of hematology Vol. 111 ( 6 ) page： 869 - 876 2020.6

Language：English Publishing type：Research paper (scientific journal)

The impact of acute and chronic graft-versus-host disease (GVHD) on clinical outcomes was retrospectively analyzed in 960 patients with non-malignant diseases (NMD) who underwent a first allogeneic hematopoietic stem cell transplantation (HSCT). Grade III-IV acute GVHD (but not grade I-II) was significantly associated with a lower rate of overall survival (OS), and higher non-relapse mortality (NRM) than that seen in patients without acute GVHD. Extensive (but not limited) GVHD was significantly associated with a lower OS rate and higher NRM than that seen in patients without chronic GVHD. Any grade of acute (but not chronic) GVHD was significantly associated with a lower incidence of relapse and a lower proportion of patients requiring a second HSCT or donor lymphocyte infusion for graft failure or mixed chimerism, but its impact on OS was almost negligible. Acute GVHD was significantly associated with lower OS rates in all disease groups, whereas chronic GVHD was significantly associated with lower OS rates in the primary immunodeficiency and histiocytosis groups. In conclusion, acute and chronic GVHD, even if mild, was associated with reduced OS in patients receiving HSCT for NMD and effective strategies should, therefore, be implemented to minimize GVHD.

DOI： 10.1007/s12185-020-02839-4

A familial case of alveolar capillary dysplasia with misalignment of the pulmonary veins: the clinicopathological features and unusual glomeruloid endothelial proliferation. Reviewed International journal Open Access

Akiko Kitano, Masato Nakaguro, Seiichi Tomotaki, Shintaro Hanaoka, Masahiko Kawai, Akiko Saito, Masahiro Hayakawa, Yoshiyuki Takahashi, Hidenori Kawasaki, Takahiro Yamada, Masahiko Ikeda, Tetsuo Onda, Kazutoshi Cho, Hironori Haga, Atsuko Nakazawa, Sachiko Minamiguchi

Diagnostic pathology Vol. 15 ( 1 ) page： 48 - 48 2020.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare disorder of pulmonary vascular abnormality with persistent pulmonary hypertension of the newborn. The symptom usually presents within hours after birth, leading to an early demise. Heterozygous de novo point mutations and genomic deletions of the FOXF1 (forkhead box F1) gene or its upstream enhancer have been identified in most patients with ACD/MPV. Most cases of ACD/MPV are sporadic; however, familial cases are also reported in 10% of patients. CASE PRESENTATION: We herein report a case of familial ACD/MPV that showed unusual glomeruloid proliferation of endothelial cells. In this family, three of the four siblings died within two to 3 days after birth because of persistent pulmonary hypertension and respiratory failure. Only the second child remains alive and healthy. An autopsy was performed for the third and fourth children, resulting in a diagnosis of ACD/MPV based on the characteristic features, including misalignment of smaller pulmonary veins and lymphangiectasis. In both of these children, glomeruloid endothelial proliferation of vessels was noted in the interlobular septa. The vessels were immunohistochemically positive for D2-40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels. CONCLUSIONS: Unusual glomeruloid endothelial proliferation was observed in a familial ACD/MPV case. This histologic feature has not been described previously in ACD/MPV or any other pulmonary disease. Although the histogenesis of this histologic feature is unclear, this finding may suggest that ACD/MPV is a compound vascular and lymphovascular system disorder that exhibits various histologic features.

DOI： 10.1186/s13000-020-00972-6

Clinical Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia: A Report from the Japan Society for Hematopoietic Cell Transplantation. Reviewed International journal Open Access

Nao Yoshida, Hirotoshi Sakaguchi, Miharu Yabe, Daiichiro Hasegawa, Asahito Hama, Daisuke Hasegawa, Motohiro Kato, Maiko Noguchi, Kiminori Terui, Yoshiyuki Takahashi, Yuko Cho, Maho Sato, Katsuyoshi Koh, Harumi Kakuda, Hiroyuki Shimada, Yoshiko Hashii, Atsushi Sato, Koji Kato, Yoshiko Atsuta, Kenichiro Watanabe

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Vol. 26 ( 5 ) page： 902 - 910 2020.5

Language：English Publishing type：Research paper (scientific journal)

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for juvenile myelomonocytic leukemia (JMML), but few large studies of HSCT for JMML exist. Using data from the Japan Society for Hematopoietic Cell Transplantation registry, we analyzed the outcomes of 129 children with JMML who underwent HSCT between 2000 and 2011. The 5-year overall survival (OS) rate and cumulative incidence of relapse were 64% and 34%, respectively. A regimen of busulfan/fludarabine/melphalan was the most commonly used (59 patients) and provided the best outcomes; the 5-year OS rate reached 73%, and the cumulative incidences of relapse and transplantation-related mortality were 26% and 9%, respectively. In contrast, the use of the irradiation-based myeloablative regimen was the most significant risk factor for OS (hazard ratio [HR], 2.92; P = .004) in the multivariate model. In addition, chronic graft-versus-host disease (GVHD) was strongly associated with lower relapse (HR, 0.37; P = .029) and favorable survival (HR, 0.22; P = .006). The current study has shown that a significant proportion of children with JMML can be cured with HSCT, especially those receiving the busulfan/fludarabine/melphalan regimen. Based on the lower relapse and better survival observed in patients with chronic GVHD, additional treatment strategies that focus on enhancing graft-versus-leukemia effects may further improve survival.

DOI： 10.1016/j.bbmt.2019.11.029

Autologous Stem Cell Transplantation for Children With Renal Tumors, and Adults With Wilms Tumor: Retrospective Analysis of the Japanese Transplant Registry Unified Management Program. Reviewed International journal

Ryoji Kobayashi, Masami Inoue, Yoshiyuki Takahashi, Atsushi Kikuta, Atsushi Ogawa, Yuhki Koga, Katsuyoshi Koh, Yoshiko Hashii, Junichi Hara, Koji Kato, Ken Tabuchi, Kimikazu Matsumoto

Journal of pediatric hematology/oncology Vol. 42 ( 4 ) page： 251 - 255 2020.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Almost all pediatric patients with renal tumors are diagnosed with nephroblastoma (Wilms tumor), clear cell sarcoma, or malignant rhabdoid tumor. The choice of treatment is important for relapsed and refractory patients with nephroblastoma. Furthermore, clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumor of the kidney (MRTK) have a poor prognosis compared with nephroblastoma. Thus, stem cell transplantation (SCT) is sometimes selected to treat these tumors. PATIENTS AND METHODS: The authors targeted a total of 84 patients with nephroblastoma, CCSK, and MRTK who underwent a first autologous SCT between 1992 and 2014, and were registered in the Japanese Transplant Registry Unified Management Program system. The authors retrospectively analyzed the SCT data for survival rate. RESULTS: Five-year overall survival rates for nephroblastoma, CCSK, and MRTK were 72.4%±6.3%, 46.8%±13.8%, and 36.4%±14.5%, respectively. The event-free survival rates at 5 years were 64.9%±6.7%, 35.7%±12.8%, and 27.3%±13.4%, respectively. The relapse rates at 5 years were 25.3%±11.4%, 46.2%±28.4%, and 60.0%±43.1%, respectively. CONCLUSION: Although the survival rate for nephroblastoma was relatively high, those of CCSK and MRTK were poor.

DOI： 10.1097/MPH.0000000000001779

ヒト-ヒト感染が疑われる肺Mycobacterium abscessus complex症の小児症例

稲垣孝行, 高橋弘泰, 山田清文, 八木哲也, 高橋義行, 村松秀城, 手塚宜行, 安立なぎさ, 豊留有香, 長田ゆかり

日本化学療法学会雑誌 Vol. 68 ( 3 ) page： 444 - 444 2020.5

droplet digital PCRを用いた若年性骨髄単球性白血病におけるサブクローナルなSETBP1とJAK3変異の検出

若松学, 村上典寛, 奥野友介, 北澤宏展, 山森彩子, 今屋雅之, 吉田太郎, 三輪田俊介, 成田幸太郎, 北澤展典, 濱田太立, 市川大輔, 谷口理恵子, 西川英里, 川島希, 成田敦, 西尾信博, 村松秀城, 小島勢二, 高橋義行

日本小児科学会雑誌 Vol. 124 ( 5 ) page： 881 - 881 2020.5

droplet digital PCRを用いた若年性骨髄単球性白血病におけるサブクローナルなSETBP1とJAK3変異の検出

日本小児科学会雑誌 Vol. 124 ( 5 ) page： 881 - 881 2020.5

Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex. Reviewed International journal

Kohji Kato, Yasuyoshi Oka, Hideki Muramatsu, Filipp F Vasilev, Takanobu Otomo, Hisashi Oishi, Yoshihiko Kawano, Hiroyuki Kidokoro, Yuka Nakazawa, Tomoo Ogi, Yoshiyuki Takahashi, Shinji Saitoh

Journal of medical genetics Vol. 57 ( 4 ) page： 245 - 253 2020.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: 3C/Ritscher-Schinzel syndrome is characterised by congenital cranio-cerebello-cardiac dysplasia, where CCDC22 and WASHC5 are accepted as the causative genes. In combination with the retromer or retriever complex, these genes play a role in endosomal membrane protein recycling. We aimed to identify the gene abnormality responsible for the pathogenicity in siblings with a 3C/Ritscher-Schinzel-like syndrome, displaying cranio-cerebello-cardiac dysplasia, coloboma, microphthalmia, chondrodysplasia punctata and complicated skeletal malformation. METHODS: Exome sequencing was performed to identify pathogenic variants. Cellular biological analyses and generation of knockout mice were carried out to elucidate the gene function and pathophysiological significance of the identified variants. RESULTS: We identified compound heterozygous pathogenic variants (c.1097dup; p.Cys366Trpfs*28 and c.2755G>A; p.Ala919Thr) in the VPS35L gene, which encodes a core protein of the retriever complex. The identified missense variant lacked the ability to form the retriever complex, and the frameshift variant induced non-sense-mediated mRNA decay, thereby confirming biallelic loss of function of VPS35L. In addition, VPS35L knockout cells showed decreased autophagic function in nutrient-rich and starvation conditions, as well as following treatment with Torin 1. We also generated Vps35l-/- mice and demonstrated that they were embryonic lethal at an early stage, between E7.5 and E10.5. CONCLUSIONS: Our results suggest that biallelic loss-of-function variants in VPS35L underlies 3C/Ritscher-Schinzel-like syndrome. Furthermore, VPS35L is necessary for autophagic function and essential for early embryonic development. The data presented here provide a new insight into the critical role of the retriever complex in fetal development.

DOI： 10.1136/jmedgenet-2019-106213

Mesenchymal stem/stromal cells stably transduced with an inhibitor of CC chemokine ligand 2 ameliorate bronchopulmonary dysplasia and pulmonary hypertension. Reviewed International journal

Toshihiko Suzuki, Yoshiaki Sato, Hidenori Yamamoto, Taichi Kato, Yuma Kitase, Kazuto Ueda, Haruka Mimatsu, Yuichiro Sugiyama, Atsuto Onoda, Shigeki Saito, Yoshiyuki Takahashi, Takayuki Nakayama, Masahiro Hayakawa

Cytotherapy Vol. 22 ( 4 ) page： 180 - 192 2020.4

Language：English Publishing type：Research paper (scientific journal)

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.

DOI： 10.1016/j.jcyt.2020.01.009

Clinical Characteristics and Treatment Outcomes of Pediatric Patients with Non-Hodgkin Lymphoma in East Asia. Reviewed International journal Open Access

Jin Kyung Suh, Yi-Jin Gao, Jing-Yan Tang, Shiann-Tarng Jou, Dong-Tsamn Lin, Yoshiyuki Takahashi, Seiji Kojima, Ling Jin, Yonghong Zhang, Jong Jin Seo

Cancer research and treatment : official journal of Korean Cancer Association Vol. 52 ( 2 ) page： 359 - 368 2020.4

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The presentations and geographic incidence of pediatric non-Hodgkin lymphoma (NHL) differ from those of adults. This study delineated the characteristics and outcomes of pediatric NHL in East Asia. MATERIALS AND METHODS: Medical records of 749 pediatric patients with NHL treated at participating institutions in mainland China, Japan, Korea, and Taiwan from January 2008 to December 2013 were reviewed. Demographic and clinical features, survival outcomes, and putative prognostic factors were analyzed. RESULTS: Five hundred thirty patients (71%) were male. The most common pathologic subtypes were Burkitt lymphoma (BL) (36%). Six hundred seven patients (81%) had advanced diseases at diagnosis. The 5-year overall survival and event-free survival (EFS) rates were 89% and 84%. The 5-year EFS rates of BL, lymphoblastic lymphoma, and diffuse large B-cell lymphoma were 88%, 88%, and 89%, and those of anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma (PTCL) were 71% and 56% (p < 0.001). Central nervous system involvement, high lactate dehydrogenase level (> 250 IU/mL), and advanced disease at diagnosis (≥ stage III) were associated with poor outcomes (p < 0.05). ALCL and PTCL relapsed more frequently than other pathologic subtypes (p < 0.001). CONCLUSION: In East Asia, PTCL was more frequent than in Western countries, and bone marrow involvement did not affect treatment outcome. This international study should motivate future collaborative study on NHL in East Asia.

DOI： 10.4143/crt.2019.219

【小児血液・腫瘍疾患の最前線】診療のトピックス高リスク神経芽腫に対するGD2抗体療法

高橋義行

小児科診療 Vol. 83 ( 4 ) page： 455 - 458 2020.4

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(株)診断と治療社

●神経芽腫に対する免疫療法の標的分子として、ジシアロガングリオシドGD2抗原タンパクに対するモノクローナル抗体がGD2抗体である。●治療毒性(疼痛、アレルギー反応、血管漏出症候群など)があるものの管理は可能で、欧米ではすでに高リスク神経芽腫の標準治療薬として保険承認されている。●わが国では米国製剤、欧州製剤ともに治験が行われており、ドラッグラグ解消のため早期承認が望まれている。(著者抄録)

Novel compound heterozygous MCOLN1 mutations identified in a Japanese girl with severe developmental delay and thin corpus callosum. Reviewed International journal

Naoya Yamaguchi, Kyoko Ban, Atsushi Suzuki, Yuji Nakamura, Kohji Kato, Hideki Muramatsu, Yusuke Okuno, Ayako Hattori, Tadashi Kaname, Yoshiyuki Takahashi, Shinji Saitoh

Brain & development Vol. 42 ( 3 ) page： 298 - 301 2020.3

Language：English Publishing type：Research paper (scientific journal)

Mucolipidosis type IV (MLIV) is a rare lysosomal storage disorder causing severe psychomotor developmental delay and progressive visual impairment. MLIV is an autosomal recessive disease caused by mutations in MCOLN1, which encodes for mucolipin-1. Here, we report a case of a 4-year-old Japanese girl with severe intellectual disability and motor deficits. Brain magnetic resonance imaging showed signal abnormalities in the white matter and thinning of the corpus callosum. Whole-exome sequencing was performed on the proband and her parents, and novel compound heterozygous mutations at c.936_938del (p.Phe313del) and c.1503dupC (p.Ile502Hisfs*106) in MCOLN1 (NM_020533.2) were identified in the proband. Additional biochemical examinations revealed elevated serum gastrin level and iron deficiency anemia, leading to the diagnosis of MLIV. More reports of such pathogenic mutations are expected to broaden the understanding of the channel function of mucolipin-1 and genotype-phenotype correlations.

DOI： 10.1016/j.braindev.2019.12.003