2023/09/21 更新

写真a

ワカマツ マナブ
若松 学
WAKAMATSU Manabu
所属
医学部附属病院 小児科 助教
大学院担当
大学院医学系研究科
職名
助教

学位 1

  1. 博士(医学) ( 2022年3月   名古屋大学 ) 

研究分野 3

  1. ライフサイエンス / 免疫学

  2. ライフサイエンス / 胎児医学、小児成育学

  3. ライフサイエンス / 血液、腫瘍内科学

現在の研究課題とSDGs 2

  1. 若年性骨髄単球性白血病

  2. 先天性免疫異常症

学歴 2

  1. 名古屋大学   医学系研究科   発育・加齢医学小児科学

    2018年4月 - 2022年3月

  2. 東北大学   医学部   医学科

    2006年4月 - 2012年3月

所属学協会 6

  1. 日本小児科学会

  2. 日本血液学会

  3. 日本造血・免疫細胞療法学会

  4. 日本小児血液・がん学会

  5. 日本免疫不全・自己炎症学会

  6. 日本輸血・細胞治療学会

▼全件表示

受賞 7

  1. 令和5年度日本血液学会奨励賞

    2023年10月   日本血液学会  

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    受賞区分:国内学会・会議・シンポジウム等の賞 

  2. 日本小児血液・がん学会 第13回学術賞

    2023年9月   日本小児血液・がん学会   TREC/KREC Newborn Screening followed by Next‑Generation Sequencing for Severe Combined Immunodeficiency in Japan

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    受賞区分:国内学会・会議・シンポジウム等の賞 

  3. 順清会 研究奨励賞

    2021年10月  

  4. 令和元年度名古屋大学医学系研究科 医学奨励賞

    2021年2月  

  5. 第277回日本小児科学会東海地方会 優秀演題賞

    2019年11月  

  6. 第55回中部日本小児科学会 特別賞

    2019年8月  

  7. 第10回JSH国際シンポジウム 優秀賞

    2019年5月  

▼全件表示

 

論文 28

  1. TREC/KREC Newborn Screening followed by Next-Generation Sequencing for Severe Combined Immunodeficiency in Japan 査読有り 国際誌

    Wakamatsu Manabu, Kojima Daiei, Muramatsu Hideki, Okuno Yusuke, Kataoka Shinsuke, Nakamura Fumiko, Sakai Yoshimi, Tsuge Ikuya, Ito Tsuyoshi, Ueda Kazuto, Saito Akiko, Morihana Eiji, Ito Yasuhiko, Ohashi Naoki, Tanaka Makito, Tanaka Taihei, Kojima Seiji, Nakajima Yoko, Ito Tetsuya, Takahashi Yoshiyuki

    JOURNAL OF CLINICAL IMMUNOLOGY   42 巻 ( 8 ) 頁: 1696 - 1707   2022年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Clinical Immunology  

    Purpose: The aim of this study is to evaluate the usefulness of T cell receptor excision circle (TREC) and/or kappa-deleting recombination excision circle (KREC) measurements integrated with diagnostic next-generation sequencing (NGS) analysis using a severe combined immunodeficiency (SCID) newborn screening (NBS) program. Methods: TREC and/or KREC values were measured in 137,484 newborns between April 2017 and December 2021 using EnLite TREC (n = 80,791) or TREC/KREC kits (n = 56,693). For newborns with positive screening results, diagnostic NGS analysis was performed with a 349-gene panel to detect genetic mutations associated with primary immunodeficiencies (PIDs). Results: A total of 145 newborns (0.11%) had abnormal TREC and/or KREC values, and a genetic diagnosis was established in 2 patients with SCID (1 in 68,742 newborns) (IL2RG-SCID and reticular dysgenesis) and 10 with non-SCID PIDs with T and/or B cell deficiencies (1 in 13,748 newborns) using NGS analysis. Furthermore, TREC values of 2849 newborns were measured and confirmed the significant correlation between the results of both TREC and TREC/KREC kits (P < 0.001) and naïve T cell counts. Conclusions: We performed the first large-scale TREC and TREC/KREC NBS programs in Japan. Our NBS programs followed by the diagnostic NGS analysis for newborns with abnormal TREC and/or KREC values are useful for the early identification and rapid molecular evaluation of not only SCID but also different non-SCID PIDs.

    DOI: 10.1007/s10875-022-01335-0

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  2. Vedolizumab for children with intestinal graft-versus-host disease: a case report and literature review

    Fukuta Taro, Muramatsu Hideki, Yamashita Daiki, Sajiki Daichi, Maemura Ryo, Tsumura Yusuke, Yamamori Ayako, Imaya Masayuki, Wakamatsu Manabu, Nishikawa Eri, Narita Kotaro, Kataoka Shinsuke, Taniguchi Rieko, Narita Atsushi, Nishio Nobuhiro, Takahashi Yoshiyuki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   118 巻 ( 3 ) 頁: 411 - 417   2023年9月

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    記述言語:英語   出版者・発行元:International Journal of Hematology  

    Acute graft-versus-host disease (aGVHD) is a challenging complication of allogeneic hematopoietic stem cell transplantation, and alternative therapies for patients showing inadequate response to steroids are limited. Vedolizumab, an anti-α4β7 integrin antibody widely used for treating inflammatory bowel diseases, has recently been studied in adult patients with steroid-refractory intestinal aGVHD. However, few studies have examined its safety and effectiveness in pediatric patients with intestinal aGVHD. We report the case of a male patient with intestinal late-onset aGVHD treated with vedolizumab. He underwent allogeneic cord blood transplantation for warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and developed intestinal late-onset aGVHD 31 months after transplantation. The patient was refractory to steroids; however, vedolizumab was initiated 43 months after transplantation (at the age of 7 years) and the symptoms of intestinal aGVHD were alleviated. Additionally, favorable endoscopic findings were observed, such as reduction of erosion and regenerative epithelial growth. We also evaluated the efficacy of vedolizumab in 10 patients with intestinal aGVHD (9 from the literature review and the present case). Six patients (60%) showed an objective response to vedolizumab. No serious adverse events were observed in any patients. Vedolizumab is a potential treatment option for steroid-refractory intestinal aGVHD in pediatric patients.

    DOI: 10.1007/s12185-023-03590-2

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  3. Two Cases of Juvenile Myelomonocytic Leukemia and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

    Yamamoto Hiroyuki, Natsume Jun, Kaneko Kimihiko, Takahashi Toshiyuki, Wakamatsu Manabu, Ogawa Chikako, Kumai Sumire, Suzui Ryosuke, Sawamura Fumi, Shiraki Anna, Nakata Tomohiko, Kidokoro Hiroyuki, Muramatsu Hideki, Takahashi Yoshiyuki

    PEDIATRIC NEUROLOGY   144 巻   頁: 1 - 4   2023年7月

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    記述言語:英語   出版者・発行元:Pediatric Neurology  

    Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder that often manifests after infections or vaccinations. We report two patients who developed MOGAD out of eight patients with juvenile myelomonocytic leukemia (JMML) that has never been reported. Methods: We investigated two patients with JMML who developed MOGAD among 127 patients with leukemia from 2012 to 2021. Results: Patient 1 was treated for JMML and developed fever and impaired consciousness at two years and one month of age. Magnetic resonance imaging revealed high-intensity lesions in the left frontal and left occipital white matter. The serum anti-MOG antibody test was positive, while the test was negative in the stored serum 45 days before the onset of encephalopathy. He had relapse of MOGAD after steroid therapy and plasmapheresis. Patient 2, who was treated for JMML, became apathetic and mute at three years and seven months of age. Magnetic resonance imaging revealed left frontoparietal subcortical high-intensity lesions. Anti-MOG antibody at the onset of encephalopathy was positive, while it was negative in stored serum 57 days before and 47 days after the onset. Conclusion: We treated two patients who developed MOGAD out of eight patients with JMML and none with MOGAD out of 119 patients with acute lymphocytic leukemia, acute myelocytic leukemia, or chronic myelocytic leukemia. The activated autoimmune process via the RAS pathway abnormality may have led to the formation of the anti-MOG antibody and the onset of MOGAD. MOGAD can occur in children with JMML, and abnormalities of the RAS pathway possibly contribute to its onset.

    DOI: 10.1016/j.pediatrneurol.2023.03.002

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  4. Human leukocyte antigen 7/8-matched unrelated bone marrow transplantation using anti-thymocyte globulin in children

    Hamada Motoharu, Muramatsu Hideki, Torii Yuka, Suzuki Kyogo, Narita Atsushi, Yoshida Taro, Imaya Masayuki, Yamamori Ayako, Wakamatsu Manabu, Miwata Shunsuke, Narita Kotaro, Kataoka Shinsuke, Kawashima Nozomu, Taniguchi Rieko, Nishikawa Eri, Nishio Nobuhiro, Ito Yoshinori, Kojima Seiji, Takahashi Yoshiyuki

    INTERNATIONAL JOURNAL OF HEMATOLOGY   118 巻 ( 1 ) 頁: 125 - 130   2023年7月

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    記述言語:英語   出版者・発行元:International Journal of Hematology  

    Human leukocyte antigen (HLA) mismatched unrelated donor transplantation is associated with an increased risk of graft-versus-host disease, graft failure, and infection, which increases post-transplant morbidity and mortality. In this single-center retrospective study, outcomes were evaluated in 30 consecutive children who underwent bone marrow transplantation (BMT) from HLA 1 allele-mismatched (HLA 7/8-matched) unrelated donors with rabbit anti-thymocyte globulin (rATG) as graft-versus-host disease (GVHD) prophylaxis. The 3-year overall survival (OS), event-free survival (EFS), and GVHD-relapse-free survival rates were 91.7% (95% CI 70.5%–91.9%), 88.3% (95% CI 67.5%–96.1%), and 73.9% (95% CI 52.4%–86.8%), respectively. Grade II–IV and III–IV acute GVHD occurred in 10 (33%) and 2 (7.0%) patients, respectively. The 3-year cumulative incidence of chronic GVHD was 7.8%. No fatal viral infections occurred. The study results show the feasibility of HLA 7/8-matched unrelated BMT with ATG to achieve favorable outcomes and acceptable GVHD, especially for patients who lack a fully matched donor.

    DOI: 10.1007/s12185-023-03571-5

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  5. Hematological abnormalities in Jacobsen syndrome: Cytopenia of varying severities and morphological abnormalities in peripheral blood and bone marrow.

    Yamashita D, Muramatsu H, Narita A, Wakamatsu M, Tsumura Y, Sajiki D, Maemura R, Yamamori A, Imaya M, Narita K, Kataoka S, Taniguchi R, Nishio N, Okuno Y, Fujita N, Koh K, Umeda K, Morihana E, Iwafuchi H, Ito M, Kojima S, Hama A, Takahashi Y

    Haematologica     2023年6月

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    記述言語:英語  

    DOI: 10.3324/haematol.2022.282513

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  6. Different effects of thymoglobulin on acute leukemia with pre-transplant residual blasts in HLA mismatch transplantation 査読有り

    Wakamatsu Manabu, Murata Makoto, Kanda Junya, Fukushima Kentaro, Fukuda Takahiro, Najima Yuho, Katayama Yuta, Ozawa Yukiyasu, Tanaka Masatsugu, Kanda Yoshinobu, Eto Tetsuya, Takada Satoru, Kako Shinichi, Uchida Naoyuki, Kawakita Toshiro, Yoshiko Hashii, Ichinohe Tatsuo, Atsuta Yoshiko, Terakura Seitaro

    INTERNATIONAL JOURNAL OF HEMATOLOGY   117 巻 ( 6 ) 頁: 889 - 899   2023年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Hematology  

    Anti-thymocyte globulin (ATG) is widely used to reduce acute and chronic graft-versus-host disease (a/cGVHD), one of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). As the removal of alloreactive T cells by ATG may also reduce the graft-versus-leukemia effect, the question of whether ATG use affects relapse incidence and survival outcomes in acute leukemia patients with pre-transplant bone marrow residual blasts (PRB) remains controversial. Here, we evaluated the impact of ATG on transplant outcomes in acute leukemia patients with PRB (n = 994) who underwent HSCT from HLA 1-allele mismatched unrelated donors (MMUD) or HLA 1-antigen mismatched related donors (MMRD). In MMUD with PRB (n = 560), multivariate analysis demonstrated that ATG use significantly decreased grade II–IV aGVHD (hazard ratio [HR], 0.474; P = 0.007) and non-relapse mortality (HR, 0.414; P = 0.029) and marginally improved extensive cGVHD (HR, 0.321; P = 0.054) and GVHD-free/relapse-free survival (HR, 0.750; P = 0.069). We concluded that ATG had different effects on transplant outcomes using MMRD and MMUD, and its use would be beneficial to decrease a/cGVHD without increasing non-relapse mortality and relapse incidence in acute leukemia patients with PRB following HSCT from MMUD.

    DOI: 10.1007/s12185-023-03563-5

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  7. Clinical and molecular features of CBL-mutated juvenile myelomonocytic leukemia.

    Yoshida T, Muramatsu H, Wakamatsu M, Sajiki D, Murakami N, Kitazawa H, Okamoto Y, Taniguchi R, Kataoka S, Narita A, Hama A, Okuno Y, Takahashi Y

    Haematologica     2023年5月

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    記述言語:英語  

    DOI: 10.3324/haematol.2022.282385

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  8. Successful treatment of DOCK8 deficiency by allogeneic hematopoietic cell transplantation from alternative donors

    Kono Asuka, Wakamatsu Manabu, Umezawa Yoshihiro, Muramatsu Hideki, Fujiwara Hiroki, Tomomasa Dan, Inoue Kento, Hattori Keiichiro, Mitsui Tetsuo, Takada Hidetoshi, Minegishi Yoshiyuki, Takahashi Yoshiyuki, Yamamoto Masahide, Mori Takehiko, Kanegane Hirokazu

    INTERNATIONAL JOURNAL OF HEMATOLOGY     2023年5月

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    記述言語:英語   出版者・発行元:International Journal of Hematology  

    Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare autosomal recessive inborn error of immunity (IEI) characterized by eczematous dermatitis, elevated serum IgE, and recurrent infections, comprising a seemingly hyper-IgE syndrome (HIES). DOCK8 deficiency is only curable with allogeneic hematopoietic cell transplantation (HCT), but the outcome of HCT from alternative donors is not fully understood. Here, we describe the cases of two Japanese patients with DOCK8 deficiency who were successfully treated by allogeneic HCT from alternative donors. Patient 1 underwent cord blood transplantation at the age of 16 years, and Patient 2 underwent haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide at the age of 22 years. Each patient received a fludarabine-based conditioning regimen. Their clinical manifestations, including refractory molluscum contagiosum, promptly improved post-HCT. They achieved successful engraftment and immune reconstitution without serious complications. Alternative donor sources such as cord blood and haploidentical donors can be options for allogeneic HCT for DOCK8 deficiency.

    DOI: 10.1007/s12185-023-03613-y

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  9. Juvenile Hemochromatosis With Non-transfused Hemolytic Anemia Caused by a De Novo PIEZO1 Gene Mutation

    Imashuku Shinsaku, Suemori Shin-ichiro, Wakamatsu Manabu, Okuno Yusuke, Muramatsu Hideki, Makino Shigeru, Miyoshi Takashi, Chonabayashi Kazuhisa, Kanno Hitoshi

    JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY   45 巻 ( 4 ) 頁: E510 - E513   2023年5月

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    記述言語:英語   出版者・発行元:Journal of Pediatric Hematology/Oncology  

    Differential diagnosis of juvenile hemochromatosis along with hemolytic anemia is often difficult. We report a 23-year-old woman with macrocytic hemolytic anemia with iron overload. The patient showed high serum ferritin and transferrin saturation and low serum transferrin and ceruloplasmin. We also noticed stomatocytes in her blood smear, which was confirmed by scanning electron microscopy. Target gene sequencing identified a mutation in PIEZO1 (heterozygous c.6008C>A: p.A2003D). This mutation was reported previously in a family with dehydrated hereditary stomatocytosis (DHS1, [OMIM 194380]), but in the current case, it was identified to be a de novo mutation. We underscore DHS1 in the differential diagnosis of iron overload associated with non-Transfused hemolytic anemia in children and young adults.

    DOI: 10.1097/MPH.0000000000002639

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  10. Germline and somatic RUNX1 variants in a pediatric bone marrow failure cohort

    Yamamori Ayako, Hamada Motoharu, Muramatsu Hideki, Wakamatsu Manabu, Hama Asahito, Narita Atsushi, Tsumura Yusuke, Yoshida Taro, Doi Takehiko, Terada Kazuki, Higa Takeshi, Yamamoto Nobuyuki, Miura Hiroki, Shiota Mitsutaka, Watanabe Kenichiro, Yoshida Nao, Maemura Ryo, Imaya Masayuki, Miwata Shunsuke, Narita Kotaro, Kataoka Shinsuke, Taniguchi Rieko, Suzuki Kyogo, Kawashima Nozomu, Nishio Nobuhiro, Iwafuchi Hideto, Ito Masafumi, Kojima Seiji, Okuno Yusuke, Takahashi Yoshiyuki

    AMERICAN JOURNAL OF HEMATOLOGY   98 巻 ( 5 ) 頁: E102 - E105   2023年5月

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    記述言語:英語   出版者・発行元:American Journal of Hematology  

    DOI: 10.1002/ajh.26874

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  11. Japanese siblings with cartilage-hair hypoplasia exhibiting different severity

    Kumagai Naonori, Funato Yusuke, Wakamatsu Manabu, Muramatsu Hideki, Mizuno Haruo

    PEDIATRICS INTERNATIONAL   65 巻 ( 1 ) 頁: e15557   2023年1月

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    記述言語:英語   出版者・発行元:Pediatrics International  

    DOI: 10.1111/ped.15557

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  12. TREATMENT-RELATED TOXICITY OF ANTI-GD2 ANTIBODY IMMUNOTHERAPY AFTER ALLOGENEIC STEM CELL TRANSPLANTATION IN HIGH-RISK NEUROBLASTOMA PATIENTS

    Kataoka Shinsuke, Yamamori Ayako, Imaya Masayuki, Wakamatsu Manabu, Narita Kotaro, Taniguchi Rieko, Narita Atsushi, Muramatsu Hideki, Nishio Nobuhiro, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   69 巻   2022年11月

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  13. CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY FOLLOWED BY UR-BMT IN TYROSINE KINASE INHIBITOR RESISTANT PEDIATRIC PH1-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA

    Imaya Masayuki, Narita Atsushi, Nishio Nobuhiro, Wakamatsu Manabu, Taniguchi Rieko, Kataoka Shinsuke, Muramatsu Hideki, Ichikawa Daisuke, Maeda Naoko, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   69 巻   2022年11月

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  14. INFANT WITH NEUROBLASTOMA STAGE 4S REQUIRING LIVING DONOR LIVER TRANSPLANTATION

    Yamamori Ayako, Muramatsu Hideki, Wakamatsu Manabu, Kataoka Shinsuke, Tsuyuki Yuta, Nishio Nobuhiro, Shimoyama Yoshie, Karube Kennosuke, Ogura Yasuhiro, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   69 巻   2022年11月

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  15. LI-FRAUMENI SYNDROME DIAGNOSED BY ONCOGENE PANEL TESTING FOR RHABDOMYOSARCOMA

    Taniguchi Rieko, Narita Atsushi, Muramatsu Hideki, Yamashita Daiki, Sajiki Daichi, Imaya Masayuki, Wakamatsu Manabu, Narita Kotaro, Nishio Nobuhiro, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   69 巻   2022年11月

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  16. RISK FACTORS FOR BLOOD STREAM INFECTIONS AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN

    Sajiki Daichi, Muramatsu Hideki, Wakamatsu Manabu, Narita Kotaro, Kataoka Shinsuke, Taniguchi Rieko, Narita Atsushi, Nishio Nobuhiro, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   69 巻   2022年11月

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  17. THE DISAPPEARANCE OF MINIMAL RESIDUAL DISEASE IN BONE MARROW DEMONSTRATES GRAFT VERSUS NEUROBLASTOMA EFFECT AFTER KIR-LIGAND MISMATCHED ALLOGENEIC CBT

    Alahmadi Rowaida, Nishio Nobuhiro, Wakamatsu Manabu, Kataoka Shinsuke, Narita Kotaro, Taniguchi Rieko, Narita Atsushi, Muramatsu Hideki, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   69 巻   2022年11月

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  18. THREE CASES OF ABNORMAL TREC VALUES WITH COPY NUMBER ALTERATIONS IDENTIFIED IN SCID NEWBORN SCREENING PROGRAM

    Wakamatsu Manabu, Muramatsu Hideki, Kojima Daiei, Okuno Yusuke, Kataoka Shinsuke, Nakamura Tomiko, Sakai Yoshimi, Nakajima Yoko, Ito Tetsuya, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   69 巻   2022年11月

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  19. Clinical parameter-based prediction of DNA methylation classification generates a prediction model of prognosis in patients with juvenile myelomonocytic leukemia

    Imaizumi Takahiro, Meyer Julia, Wakamatsu Manabu, Kitazawa Hironobu, Murakami Norihiro, Okuno Yusuke, Yoshida Taro, Sajiki Daichi, Hama Asahito, Kojima Seiji, Takahashi Yoshiyuki, Loh Mignon, Stieglitz Elliot, Muramatsu Hideki

    SCIENTIFIC REPORTS   12 巻 ( 1 ) 頁: 14753   2022年8月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    Juvenile myelomonocytic leukemia (JMML) is a rare heterogeneous hematological malignancy of early childhood characterized by causative RAS pathway mutations. Classifying patients with JMML using global DNA methylation profiles is useful for risk stratification. We implemented machine learning algorithms (decision tree, support vector machine, and naïve Bayes) to produce a DNA methylation-based classification according to recent international consensus definitions using a well-characterized pooled cohort of patients with JMML (n = 128). DNA methylation was originally categorized into three subgroups: high methylation (HM), intermediate methylation (IM), and low methylation (LM), which is a trichotomized classification. We also dichotomized the subgroups as HM/IM and LM. The decision tree model showed high concordances with 450k-based methylation [82.3% (106/128) for the dichotomized and 83.6% (107/128) for the trichotomized subgroups, respectively]. With an independent cohort (n = 72), we confirmed that these models using both the dichotomized and trichotomized classifications were highly predictive of survival. Our study demonstrates that machine learning algorithms can generate clinical parameter-based models that predict the survival outcomes of patients with JMML and high accuracy. These models enabled us to rapidly and effectively identify candidates for augmented treatment following diagnosis.

    DOI: 10.1038/s41598-022-18733-4

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  20. Whole-exome analysis of 177 pediatric patients with undiagnosed diseases

    Narita Kotaro, Muramatsu Hideki, Narumi Satoshi, Nakamura Yuji, Okuno Yusuke, Suzuki Kyogo, Hamada Motoharu, Yamaguchi Naoya, Suzuki Atsushi, Nishio Yosuke, Shiraki Anna, Yamamori Ayako, Tsumura Yusuke, Sawamura Fumi, Kawaguchi Masahiro, Wakamatsu Manabu, Kataoka Shinsuke, Kato Kohji, Asada Hideyuki, Kubota Tetsuo, Muramatsu Yukako, Kidokoro Hiroyuki, Natsume Jun, Mizuno Seiji, Nakata Tomohiko, Inagaki Hidehito, Ishihara Naoko, Yonekawa Takahiro, Okumura Akihisa, Ogi Tomoo, Kojima Seiji, Kaname Tadashi, Hasegawa Tomonobu, Saitoh Shinji, Takahashi Yoshiyuki

    SCIENTIFIC REPORTS   12 巻 ( 1 ) 頁: 14589   2022年8月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24–35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

    DOI: 10.1038/s41598-022-14161-6

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  21. A patient with very early onset FH-deficient renal cell carcinoma diagnosed at age seven

    Taniguchi R., Muramatsu H., Okuno Y., Yoshida T., Wakamatsu M., Hamada M., Shirota C., Sumida W., Hinoki A., Tainaka T., Gotoh Y., Tsuzuki T., Tanaka Y., Kojima S., Uchida H., Takahashi Y.

    Familial Cancer   21 巻 ( 3 ) 頁: 337 - 341   2022年7月

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    記述言語:日本語   出版者・発行元:Familial Cancer  

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline variants in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). HLRCC-associated RCC usually occurs in the middle age, with the median age being 40–44 years. This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering well without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in the FH gene and its loss of heterozygosity in the tumor. At nine years (114 months) of age, the male patient showed no recurrence of the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

    DOI: 10.1007/s10689-021-00268-8

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  22. Combination chemotherapy consisting of irinotecan, etoposide, and carboplatin for refractory or relapsed neuroblastoma

    Imaya Masayuki, Muramatsu Hideki, Narita Atsushi, Yamamori Ayako, Wakamatsu Manabu, Yoshida Taro, Miwata Shunsuke, Narita Kotaro, Ichikawa Daisuke, Hamada Motoharu, Nishikawa Eri, Kawashima Nozomu, Nishio Nobuhiro, Kojima Seiji, Takahashi Yoshiyuki

    CANCER MEDICINE   11 巻 ( 9 ) 頁: 1956 - 1964   2022年5月

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    記述言語:日本語   出版者・発行元:Cancer Medicine  

    Background: Patients with primary refractory and relapsed neuroblastoma have a poor prognosis since safe and effective chemotherapies for these patients are currently limited. The development of new chemotherapy regimens for these patients is imperative to improve survival outcomes. Methods: We retrospectively analyzed 40 patients with refractory (n = 36) or relapsed (n = 4) neuroblastoma who received irinotecan, etoposide, and carboplatin (IREC) as a second-line treatment. We evaluated their therapeutic response and the toxicity of IREC. We also assessed the impact of UGT1A1 gene polymorphisms, which are involved in irinotecan metabolism, on outcomes and toxicity. Results: A total of 112 cycles of IREC were administered to 40 patients with a median of 2 cycles per patient (range, 1–9). Six (15%) patients (UGT1A1 wild-type [n = 2] and heterozygous [n = 4]) showed objective responses, including partial response (n = 1), tumor shrinkage (n = 4), and improved findings on their MIBG scan (n = 1). Grade 4 neutropenia, grade 4 leukopenia, and grades 3–4 gastrointestinal toxicity were observed in 110 (98%), 88 (79%), and 3 (3%) cycles, respectively. There was no IREC-related mortality. Patients with UGT1A1 polymorphisms showed a higher frequency of grade 4 leukopenia, but these patients did not have increased treatment-related mortality or non-hematologic toxicity. Conclusions: IREC showed an objective response rate of 15% including 1 case with partial response. IREC was well tolerated regardless of UGT1A1 genotype. This study suggests that IREC is a promising second-line chemotherapy for refractory or relapsed neuroblastoma.

    DOI: 10.1002/cam4.4529

    Web of Science

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  23. Minor PNH clones do not distinguish inherited bone marrow failure syndromes from immune-mediated aplastic anemia 査読有り

    Narita Atsushi, Miwata Shunsuke, Imaya Masayuki, Tsumura Yusuke, Yamamori Ayako, Wakamatsu Manabu, Hamada Motoharu, Taniguchi Rieko, Okuno Yusuke, Muramatsu Hideki, Takahashi Yoshiyuki

    BLOOD ADVANCES   6 巻 ( 8 ) 頁: 2517 - 2519   2022年4月

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    記述言語:英語   出版者・発行元:Blood Advances  

    DOI: 10.1182/bloodadvances.2021006044

    Web of Science

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  24. A retrospective analysis of azacitidine treatment for juvenile myelomonocytic leukemia

    Honda Y., Muramatsu H., Nanjo Y., Hirabayashi S., Meguro T., Yoshida N., Kakuda H., Ozono S., Wakamatsu M., Moritake H., Yasui M., Sano H., Manabe A., Sakashita K.

    International Journal of Hematology   115 巻 ( 2 ) 頁: 263 - 268   2022年2月

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    記述言語:日本語   出版者・発行元:International Journal of Hematology  

    Juvenile myelomonocytic leukemia (JMML) is a pediatric hematological malignancy with a poor prognosis. Although several case series have been published describing hematological and molecular responses to azacitidine (AZA) treatment in patients with JMML, the efficacy and safety profile of AZA is not well investigated, especially in Asian children and children undergoing hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 5 patients who received a total of 12 cycles (median 2 cycles) of AZA treatment in Japan. All five patients were boys and their ages at the time of treatment were 21, 23, 24, 26, and 46 months, respectively. All five patients tolerated AZA treatment, including four patients who received AZA after HSCT. Therapeutic toxicity with AZA was mostly limited to hematological toxicity. The only serious non-hematological adverse event was hyperbilirubinemia (grades III–IV) observed in a patient who received AZA after a second HSCT. Two out of five patients treated with AZA achieved a partial response (PR), while three patients treated for post-transplant relapse did not have an objective response. Future prospective studies should be conducted to develop combination therapies with AZA and other molecular targeted drugs for high-risk patients.

    DOI: 10.1007/s12185-021-03248-x

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

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

    PEDIATRICS INTERNATIONAL   64 巻 ( 1 ) 頁: e15275   2022年1月

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    記述言語:英語   出版者・発行元:Pediatrics International  

    DOI: 10.1111/ped.15275

    Web of Science

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  26. Microsatellite instability-high is rare events in refractory pediatric solid tumors

    Yoshida T., Muramatsu H., Wakamatsu M., Taniguchi R., Ichikawa D., Nakaguro M., Natsume A., Takahashi Y.

    Pediatric Hematology and Oncology   39 巻 ( 5 ) 頁: 468 - 474   2022年

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    記述言語:英語   出版者・発行元:Pediatric Hematology and Oncology  

    Microsatellite instability (MSI)-high status is associated with good responsiveness to immune checkpoint inhibitors. Although MSI-high status has been actively investigated in pediatric brain tumors, studies of other pediatric solid tumors are lacking. Among 334 consecutive pediatric patients with solid tumors, we retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues of 36 of 74 patients (49%) who died of disease. We assessed the MSI status in these tissues using five multiplexed markers. The results revealed that none of the patients had an MSI-high status. These results indicate that MSI-high status is a rare event in pediatric patients with refractory/relapsed solid tumors. Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1998266.

    DOI: 10.1080/08880018.2021.1998266

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  27. Clinical Impact of Melphalan Pharmacokinetics on Transplantation Outcomes in Children Undergoing Hematopoietic Stem Cell Transplantation

    Maemura Ryo, Wakamatsu Manabu, Matsumoto Kana, Sakaguchi Hirotoshi, Yoshida Nao, Hama Asahito, Yoshida Taro, Miwata Shunsuke, Kitazawa Hironobu, Narita Kotaro, Kataoka Shinsuke, Ichikawa Daisuke, Hamada Motoharu, Taniguchi Rieko, Suzuki Kyogo, Kawashima Nozomu, Nishikawa Eri, Narita Atsushi, Okuno Yusuke, Nishio Nobuhiro, Kato Koji, Kojima Seiji, Morita Kunihiko, Muramatsu Hideki, Takahashi Yoshiyuki

    CELL TRANSPLANTATION   31 巻   頁: 9636897221143364   2022年

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    記述言語:英語   出版者・発行元:Cell Transplantation  

    Melphalan is widely used for hematopoietic stem cell transplantation (HSCT) conditioning. However, the relationship between its pharmacokinetic (PK) and transplantation outcomes in children has not been thoroughly investigated. We prospectively analyzed the relationship between melphalan area under the curve (AUC) and transplantation outcome and examined the development of a predictive model for melphalan clearance in children. This study included 43 children aged 0 to 19 years who underwent HSCT following a melphalan-based conditioning regimen from 2017 to 2021. In univariable analysis, high-melphalan AUC resulted in a significantly lower cumulative incidence of acute graft-versus-host disease and a higher cumulative incidence of thrombotic microangiopathy, although no significant difference was observed in survival. Regression analysis of a randomly selected derivation cohort (n = 21) revealed the following covariate PK model: predicted melphalan clearance (mL/min) = 6.47 × 24-h urinary creatinine excretion rate (CER, g/day) × 24-h creatinine clearance rate (CCR, mL/min) + 92.8. In the validation cohort (n = 22), the measured melphalan clearance values were significantly correlated with those calculated based on the prediction equation (R2 = 0.663). These results indicate that melphalan exposure may be optimized by adjusting the melphalan dose according to CER and CCR.

    DOI: 10.1177/09636897221143364

    Web of Science

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  28. Allogeneic stem cell transplantation with reduced intensity conditioning for patients with adrenoleukodystrophy 招待有り 査読有り

    MOLECULAR GENETICS AND METABOLISM REPORTS     2018年11月

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    記述言語:英語  

▼全件表示

書籍等出版物 1

  1. 胸腺低形成

    ( 担当: 単著)

    原発性免疫不全症候群診療の手引き 改訂第2版 

講演・口頭発表等 4

  1. SCID新生児マススクリーニング検査で同定したコピー数変化を伴うTREC異常値の3例

    若松 学

    第64回日本小児血液・がん学会学術集会  2022年11月26日 

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    開催年月日: 2022年11月

    記述言語:日本語  

    国名:日本国  

  2. 遺伝性骨髄不全症候群に対するプロテオミクス解析による診断検査

    若松 学

    第84回日本血液学会学術集会  2022年10月16日 

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    開催年月日: 2022年10月

    記述言語:日本語  

    国名:日本国  

  3. 愛知県における重症複合免疫不全症に対する TREC新生児マススクリーニング検査

    若松 学

    第11回日本血液学会東海地方会  2022年6月9日 

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    開催年月日: 2022年6月

    記述言語:日本語  

    国名:日本国  

  4. 愛知県におけるTREC/KRECを用いた新生児マススクリーニング検査

    若松 学

    第5回日本免疫不全・自己炎症学会総会・学術集会  2022年2月12日 

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    開催年月日: 2022年2月

    記述言語:日本語  

    国名:日本国  

共同研究・競争的資金等の研究課題 1

  1. 遺伝性骨髄不全症候群に対する網羅的プロテオミクス解析

    研究課題番号:22K15601  2022年4月 - 2024年3月

    若手研究

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

科研費 1

  1. 遺伝性骨髄不全症候群に対する網羅的プロテオミクス解析

    研究課題/研究課題番号:22K15601  2022年4月 - 2024年3月

    科学研究費助成事業  若手研究

    若松 学

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    担当区分:研究代表者 

    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    遺伝性骨髄不全症候群(Inherited Bone Marrow Failure Syndrome; IBMFS)は、貧血、血小板減少、顆粒球減少などの造血不全を合併する症候群である。多数の疾患を包括する概念であり、ファンコニ貧血、先天性角化不全症、シュワッハマン・ダイアモンド症候群などが含まれる。IBMFSには、遺伝子解析のみで診断が確定できない場合も多く、遺伝子解析を補完する技術として高深度プロテオーム解析を用いた、迅速かつ低コストの検査診断システムの構築を行う。

 

メディア報道 1

  1. 本邦初の大規模な重症複合免疫不全症(SCID)に対する TREC/KREC新生児マススクリーニング検査 ~重症複合免疫不全症の新生児に対する早期診断と治療介入が予後を改善~ 新聞・雑誌

    2022年8月

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    執筆者:本人以外