Development of new strategy for cord blood transplantation using enhancedleukemia-specific immune response with donor T cell

• Project/Area Number: 19591098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: TAKAHASHI Satoshi The University of Tokyo, 医科学研究所, 准教授 (60226834)
• Co-Investigator(Kenkyū-buntansha): WATANABE Nobukazu 東京大学, 医科学研究所, 特任助教 (10334278) ; KATO Kazunori 札幌医科大学, 医学部・, 准教授 (60233780) ; TOJO Arinobu 東京大学, 医科学研究所, 教授 (00211681) ; OOI Jun 東京大学, 医科学研究所, 助教 (20302606)
• Co-Investigator(Renkei-kenkyūsha): WATANABE Nobukazu 東京大学, 医科学研究所, 特任助教 (10334278) ; KATO Kazunori 札幌医科大学, 医学部・, 准教授 (60233780) ; TOJO Arinobu 東京大学, 医科学研究所, 教授 (00211681) ; OOI Jun 東京大学, 医科学研究所, 助教 (20302606)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 白血病 / 臍帯血移植 / 白血病特異免疫 / 移植後免疫回復 / キラー免疫グロブリン様受容体 / NK細胞受容体 / HLA-C / GVHD

Research Abstract

臍帯血移植後のTリンパ球の回復過程において、速やかにナイーヴからメモリーフェノタイプへ転換された。また、KIR-L不適合の組み合わせによる抗腫瘍免疫反応に関しては、臍帯血におけるNK細胞受容体と患者HLA-Cとの組み合わせによる、GVHDの発症頻度や再発率、生存などへの影響を見出すことはできなかった。更に、各種T細胞におけるホーミング関連分子の発現の各臓器におけるGVHDの発症様式および重症度との関連は認めなかった
以上の知見を集積することによって、臍帯血移植後の抗腫瘍特異的細胞性免疫療法における次段階の治療戦略を構築するための重要な基盤的情報となると考えた

Research Products

• [Journal Article] Unrelated cord blood transplantation after myeloablative conditioning in adults with acute myelogenous leukemia (2009)
  • Author(s): Ooi J, Takahashi S, Tomonari A, Tsukada N, Konuma T, Kato S, KasaharaS, Sato A, Monma F, Nagamura F, Iseki T, Tojo A, Asano S
  • Journal Title: Bone Marrow Transplant 43(6) Pages: 455-459
• [Journal Article] Second myeloablativeallogeneic stem cell transplantation (SCT) using cord blood for leukemia relapsedafter initial allogeneic SCT (2009)
  • Author(s): Konuma T, Ooi J, Takahashi S, Tomonari A, Tsukada N, Kato S, Sato A, Monma F, Kasahara S, Uchimaru K, IsekiT, Tojo A, Asano S.
  • Journal Title: Leuk Res 33(6) Pages: 0840-842
• [Journal Article] YamaguchiT, Asano S. Myeloablative unrelated cordblood transplantation for acute leukemiapatients between 50 and 55 years of age : single institutional retrospective (2009)
  • Author(s): Konuma T, Takahashi S, Ooi J,Tomonari A, Tsukada N, Kato S, Sato A,Monma F, Kasahara S, Nagamura-Inoue T,Uchimaru K, Iseki T, Tojo A,
  • Journal Title: comparison with patients younger than 50years of age. Ann Hematol 88(6) Pages: 581-588
• [Journal Article] Donor cell-derived myelodysplastic syndrome after cord bloodtransplantation (2009)
  • Author(s): Konuma T, Ooi J, Takahashi S,Tomonari A, Tsukada N, Kato S, Sato A, Monma F, Hongo E, Uchimaru K, Tojo A,Asano S.
  • Journal Title: Bone Marrow Transplant 43(5) Pages: 429-431
• [Journal Article] Second myeloablative allogeneic stem cell transplantation (SCT) using cord blood for leukemia relapsed after initial allogeneic SCT. (2009)
  • Author(s): Konuma T, Takahashi S, Tojo A, et al
  • Journal Title: Leuk Res 33(6) Pages: 840-842
  • Peer Reviewed
• [Journal Article] Fatalacute tumor lysis syndrome followingintrathecal chemotherapy for acute lymphoblastic leukemia with meningealinvolvement (2008)
  • Author(s): Konuma T, Ooi J, Takahashi S, Tomonari A, Tsukada N, Kato S, Sato A, Monma F, Uchimaru K, Tojo A.
  • Journal Title: Intern Med. 47(22) Pages: 1987-1988
• [Journal Article] Nooccurrence of Pneumocystis jiroveci(carinii) pneumonia in 120 adults undergoing myeloablative unrelated cordblood transplantation (2008)
  • Author(s): Tomonari A, Takahashi S, Ooi J,Tsukada N, Konuma T, Kato S, KasaharaS, Iseki T, Tojo A, Asano S.
  • Journal Title: Transpl Infect Dis 10(5) Pages: 303-307
• [Journal Article] Central nervous system leukemia on magnetic resonanceimaging (2008)
  • Author(s): Konuma T, Ooi J, Takahashi S, Tomonari A, Tsukada N, Kato S, KasaharaS, Uchimaru K, Tojo A.
  • Journal Title: Intern Med 47(5) Pages: 477
• [Journal Article] Tsukada N, Konuma T, Kato S, KasaharaS, Iseki T, Tojo A, Asano S., Bloodeosinophilia after unrelated cord blood transplantation for adults (2008)
  • Author(s): Tomonari A, Takahashi S, Ooi J
  • Journal Title: Bone MarrowTransplant 42(1) Pages: 63-65
• [Journal Article] Early renal injuryafter myeloablative cord blood transplantation in adults (2008)
  • Author(s): Mae H, Ooi J, Takahashi S, TomonariA, Tsukada N, Konuma T, Hongo E, KatoS, Kasahara S, Oiwa-Monna M, KurokawaY, Tojo A, Asano S
  • Journal Title: LeukLymphoma 49(3) Pages: 538-42
• [Journal Article] Myeloablative unrelated cord bloodtransplantation for adult acute myeloid leukemia patients with 11q23abnormalities (2008)
  • Author(s): Konuma T, Ooi J, Takahashi S, Tomonari A, Tsukada N, Kato S, KasaharaS, Uchimaru K, Iseki T, Tojo A, Asano S.
  • Journal Title: Eur J Haematol 80(6) Pages: 545-548
• [Journal Article] Impact of cytomegalovirus serostatus onoutcome of unrelated cord blood transplantation for adults : a single-institute 1experience in Japan (2008)
  • Author(s): Tomonari A, Takahashi S, Ooi J,Tsukada N, Konuma T, Kato S, KasaharaS, Iseki T, Yamaguchi T, Tojo A, Asano S
  • Journal Title: Eur J Haematol 80(3) Pages: 251-257
• [Journal Article] Nakauchi H. Recipient-derived cells aftercord blood transplantation : dynamics elucidated by multicolor FACS, reflectinggraft failure and relapse (2008)
  • Author(s): Watanabe N, Takahashi S, Ishige M, Ishii Y, Ooi J, Tomonari A, Tsukada N, Konuma T, Kato S, Sato A, Tojo A
  • Journal Title: Biol BloodMarrow Transplant 14(6) Pages: 693-701
• [Journal Article] Cardiovascular toxicity ofcryopreserved cord blood cell infusion. (2008)
  • Author(s): Konuma T, Ooi J, Takahashi S,Tomonari A, Tsukada N, Kobayashi T, Sato A, Kato S, Kasahara S, Ebihara Y, Nagamura-Inoue T, Tsuji K, Tojo A, Asano S
  • Journal Title: Bone Marrow Transplant 41(10) Pages: 861-5
• [Journal Article] Preemptive therapy with ganciclovir 5mg/kg once daily for cytomegalovirus infection after unrelated cord bloodtransplantation (2008)
  • Author(s): Tomonari A, Takahashi S, Ooi J,Tsukada N, Konuma T, Kobayashi T,Takasugi K, Iseki T, Tojo A, Asano S
  • Journal Title: Bone Marrow Transplant 41 Pages: 371-376
• [Journal Article] Unrelated cord blood transplantation after myeloablative conditioning in adults with acute myelogenous leukemia (2008)
  • Author(s): Ooi J, Takahashi S, Tojo A, et al
  • Journal Title: Biol Blood Marrow Transplant 14(12) Pages: 1341-1347
  • Peer Reviewed
• [Journal Article] Recipient-derived cells after cord blood transplantation: dynamics elucidated by multicolor FACS, reflecting graft failure and relapse. (2008)
  • Author(s): Watanabe N, Takahashi S,et al
  • Journal Title: Biol Blood Marrow Transplant 14(6) Pages: 693-701
  • Peer Reviewed
• [Journal Article] Cytogenetic remissions induced byinterferon alpha and imatinib mesylate areimmunologically distinct in chronic myeloid leukemia (2007)
  • Author(s): Nakayama S, Nagamura-Inoue T, Yokoyama K, Ohno N, Ooi J, TakahashiS, Uchimaru K, Iseki T, Tojo A
  • Journal Title: Int J Hematol.Oct 86(3) Pages: 208-11
• [Journal Article] Impact of ABO incompatibility onengraftment and transfusion requirementafter unrelated cord blood transplantation : a single institute experience in Japan. (2007)
  • Author(s): Tomonari A, Takahashi S, Ooi J,Tsukada N, Konuma T, Kobayashi T, SatoA, Iseki T, Yamaguchi T, Tojo A, Asano S.
  • Journal Title: Bone Marrow Transplant 40(6) Pages: 523-528
• [Journal Article] Early-onsetpulmonary complication showing organizing pneumonia pattern followingcord blood transplantation in adults (2007)
  • Author(s): Tomonari A, Tsukada N, Takahashi S, Ooi J, Konuma T, Kobayashi T, Fukuno K,Takasugi K, Fujii T, Endo T, Iwamoto A, Oyaizu N, Tojo A, Asano S
  • Journal Title: Int Jhematol 85(4) Pages: 364-366
• [Journal Article] Bacterial bloodstream infection inneutropenic adult patients after myeloablative cord blood transplantation : experience of a single institution in Japan (2007)
  • Author(s): Tomonari A, Takahashi S, Ooi J,Tsukada N, Konuma T, Kobayashi T, SatoA, Takasugi K, Iseki T, Tojo A, Asano S.
  • Journal Title: Int J Hematol 85(3) Pages: 238-241
• [Journal Article] Allogeneic stemcell transplantation for hepatosplenic gammadelta T-cell lymphoma (2007)
  • Author(s): Konuma T, Ooi J, Takahashi S, Tomonari A, Tsukada N, Kobayashi T,Sato A, Tojo A, Asano S
  • Journal Title: LeukLymphoma 48(3) Pages: 630-632
• [Journal Article] Comparative single-institute analysis ofcord blood transplantation from unrelateddonors with bone marrow or peripheralblood stem cell transplantation fromrelated donors in adult patients with hematological malignancies aftermyeloablative conditioning regimen (2007)
  • Author(s): Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M, Fukuno K, Uchiyama M, Takasugi K, Iseki T, Tojo A, Yamaguchi T, Asano S
  • Journal Title: Blood 109(3) Pages: 1322-1330
• [Journal Article] Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem cell transpla ntation from related donors in adult patients with hematological malignan cies after myeloablative conditioning regemen (2007)
  • Author(s): Takahashi S, et. al.
  • Journal Title: Blood 109 Pages: 1322-1330
  • Peer Reviewed
• [Journal Article] Allogeneic stem cell transplantation for hepatosplenic gammadelta T-cell lymphoma. (2007)
  • Author(s): Konuma T, Takahashi S, et. al.
  • Journal Title: Leuk Lymphoma. 48(3): Pages: 630-632
  • Peer Reviewed
• [Journal Article] Bacterial bloodstream infection in neutropenic adult patients after myeloablative cofd blood transplantation: experience of a single institution in Japan. (2007)
  • Author(s): Tomonari A, Takahashi S, et. al.
  • Journal Title: Int J Hematol 85(3): Pages: 238-41
  • Peer Reviewed
• [Journal Article] Early-onset pulmonary complication showing organizing pneumonia Pattern following cord blood transplantation in adults. (2007)
  • Author(s): Tomonari A, Takahashi S, et. al.
  • Journal Title: Int J Hematol 85(4) Pages: 364-366
  • Peer Reviewed
• [Journal Article] Impact of ABO incompatibility on engraftment and transfusion requirement after unrelated cord blood transplantation: a single institute experience in japan. (2007)
  • Author(s): Tomonari A, Takahashi S, et. al.
  • Journal Title: Bone Marrow Transplant 41 Pages: 371-376
  • Peer Reviewed
• [Journal Article] Preemptive therapy with ganciclovir 5 mg/kg once daily for cytomegalovirus infection after unrelated cord blood transplantation. (2007)
  • Author(s): Tomonari A, Takahashi S, et. al.
  • Journal Title: Bone Marrow Transplant 41 Pages: 371-376
  • Peer Reviewed
• [Presentation] Blood and Maroow Transplantation (2008)
  • Author(s): Takahashi S
  • Organizer: Cord blood for allogeneicstem cell transplantation for MDS patientsin Japan. 13^<th> Congress of Asia-Pacific
  • Place of Presentation: Taipei
  • Year and Date: 20080426-27
• [Presentation] Equivalentdisease-free survival results after CBT andBMT from unrelated donor using TBIcontaining myeloablative regimen andcalsinulin inhibitors plus MTX methods in analysis by competing risk regression models (2008)
  • Author(s): Takahashi S., et al
  • Organizer: 34th Annual Meeting of theEuropian Group for Blood and MarrowTransplantation Flolence
  • Place of Presentation: Italy
  • Year and Date: 2008-04-02
• [Presentation] CBT in Adults forMalignant Diseases in Japan (2007)
  • Author(s): Takahashi S
  • Organizer: The First Cord Blood Transplant European
  • Place of Presentation: Conference. Rome
  • Year and Date: 20070503-05
• [Presentation] CBT in Adults for Malignant Diseases in Japan (2007)
  • Author(s): Takahashi S
  • Organizer: The first cord blood transplant european conference.
  • Place of Presentation: Rome
  • Year and Date: 20070503-05
• [Book] Walters Kluwer, Curr Opin (2007)
  • Author(s): Takahashi S
  • Total Pages: 19(6) : 153
  • Publisher: Oncology
• [Book] Curr Opin Oncology 19(6) (2007)
  • Author(s): Takahashi S.
  • Total Pages: 153
  • Publisher: Walters Kiuwer