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Mechanism of graft-versus-leukemia (GVL) effect to prevent leukemia relapse after allogeneic bone marrow transplantation

Research Project

Project/Area Number 06671081
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionKanazawa University

Principal Investigator

SHIOBARA Shintaro  Kanazawa University, Blood Transfusion Section, Associate prof., 医学部・附属病院, 助教授 (10135056)

Co-Investigator(Kenkyū-buntansha) UEDA Mikio  Kanazawa University, Internal Medicine (III), Assistant Prof., 医学部, 助手 (90193812)
NAKAO Shinji  Kanazawa University, Internal Medicine (III), Assistant Prof., 医学部, 講師 (70217660)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
KeywordsBone marrow transplantation / Graft-versus-leukemia effect / Graft-versus-host disease / Donor leukocyte transfusion / T cell clone / Adoptive immuno-therapy / Allo-cell therapy / 骨髄移植 / 抗白血病(GVL)効果 / 再発予防
Research Abstract

Graft-versus-leukemia (GVL) effect is important to maintain durable remission after allogeneic marrow transplantation. We have studied mixed hematopoietic chimerism in patients with CML received alloBMT and found a small number of host-derived normal hematopoietic progenitor cells may persist after lethal chemoradiotherapy despite Ph^1-positive clones could be eradicated ; suggesting patient T cells can recognize host-derived normal progenitor cells and Ph^1-positive clone separately.
Furthermore, we disclosed (1) ; donor leukocyte infusion (DLT) can enhance this GVL effect, (2) ; eradicate leukemia clone in transplant patients with relapsing CML,(3) ; this effect was depend on disease and stage at DLT.Preliminary survey of 26 Japanese patients with relapsing leukemia after alloBMT showed the induction rate of DLT were 100% of CML in chronic phase, 50% of MDS but 0% of CML in blastic phase and 20-30% of acute leukemia.
We have studied Tcell clonotype following DLT by using PCR product of T cell receptors and found one clear band in TCRV beta15+T cells ; suggested a specific T cell may eradicate leukemia without GVHD.
In summary, these data showed allo cell therapy like DLT opened a new promising area to eradicate leukemia clone.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 高見昭良: "非血縁者間同種骨髄移植における慢性GVHD →血縁者間同種骨髄移植との比較" 臨床血液. 36. 6-11 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakao,S.: "Clonal hematopoiesis detected in allogeneic marrow recipients with poor engraftment." Transplantation. 57. 1266-1268 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山崎宏人: "同種骨髄移植後の再発に対するドナーリンパ球輸注後に急性GVHDを経過せずに寛解が得られた慢性骨髄性白血病" 臨床血液. 36. 677-681 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamaguchi,M.: "Early recovery of host-derived hemato poiesis in marrow transplant recipients conditioned with high-dose busulfan and cyclophosphamide." Bone Marrow Transplantation. 15. 787-789 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Morishima,Y.: "Low incidence of acute GVHD in patients transplanted with narrow from HLA-A,B,DR compatible unrelated donors in Japanese." Bone Marrow Transplantation. 15. 235-239 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 杉森尚美: "同種骨髄移植後重症GVHDの治療中拒絶を来たした急性骨髄性白血病の一例." 臨床血液. 37. 134-138 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakao S.et al: "Clonal hematopoiesis detected in allogeneic morrow recipient with poor engraftment" Transplantation. 57. 1266-1268 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takami Y.et al: "Analysis of chronic graft-versus-host disease after unrelated donor bone marrow transplantation." (in japanese). Japan Journal of Clinical Hematology. 36. 6-11 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamaguti M.et al: "Early recovery of host-derived hematopoiesis in marrow recipients conditioned with high-dose busulfan and cyclophosphamide" Bone Marrow Transplantation. 15. 787-789 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamazaki H.et al: "Successful treatment of recurrent chronic myelogenous leukemia in allogeneic marrow transplantation with the donor leukocyte transfusion, without induction of acute graft-versus-host disease (in japanese)" Japan journal of Clinical Hematology. 36. 677-681 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Morishima Y.et al: "Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR compatible unrelated donors in japanese" Bone Marrow Transplantation. 15. 235-239 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sugimori N.et al: "Rejection of an allogeneic bone marrow graft following successful treatment of severe graft-versus-host disease (in japanese)" Japan journal of Clinical Hematology. 37. 134-138 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kodera Y,et al: "Analysis of 55 transplants from unrelated volunteer donors facilitated by Thokai Marrow Donor Bank" Internal Medicine. 35. 78-83 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 山崎宏人: "同種骨髄移植後の再発に対するドナーリンパ球輸注後に急性GVHDを経過せずに寛解が得られた慢性骨髄性白血病" 臨床血液. 36. 677-681 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 杉森尚美: "同種骨髄移植後単症GVHDの治療中拒絶を来たした急性骨髄性白血病の一例" 臨床血液. 37. 134-138 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yamaguchi M.: "Early recovery of host-derived hematopoiesis in marrow transplant recipicuts Londitioned with high-dose busuifan and cyclophcsphamide." Bone Marrow-Transplantation. 15. 787-789 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Morishima Y.: "Low incidence of acuite GVHD in patients transplanted with marrow from HLA-A,B,DR colnpatiwe unrelated donors in Japanese." Bone Marrow-Transplantation. 15. 235-239 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kodera Y.: "Analysis of 55 Transplants from unrelated volunteer donors facilitated by Thokai Marrow Donor Bank." Internal Medicine. 35. 78-83 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 高見,昭良: "非血縁者間同種骨髄移植における慢性GVHD-血縁者間同種骨髄移植との比較" 臨床血液. 36. 6-11 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Yamaguchi: "Quality of hematologic recovery in patients with aplastic anemia after cyclosporine the rapy." Experimental of Haematology. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Nakao: "Clonal hematopoiesis detected in allogeneic marrow recipient with poor engraftment." Transpantation. 57. 1266-1268 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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