A study on donor lymphocyte infusion for the prophylaxis or the treatment of leukemia relapse after allogeneic bone marrow transplantation
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Teikyo University|
YABE Hiromasa Tokai University, Pediatrics Assistant professor, 医学部, 講師 (70220217)
YABE Miharu Tokai University, Pediatrics Assistant professor, 医学部, 講師 (40172514)
KATO Shun-ichi Tokai University, Pediatrics Associate professor, 医学部, 助教授 (70096212)
|Project Period (FY)
1997 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1999 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1998 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
|Keywords||stem cell transplantation / cellular immunity / GVHD / donor lymphocyte infusion / Ebstein-Barr virus / BLPD / CTL / Stem cell transplantation / Epstein-Barr virus / allogeneic BMT / IFN-γ / IL-12 / EBV-BLPD / DLT / IFN-_γ|
I. Blastogenesis of peripheral blood lymphocytes in bone marrow graft recipients against IL-2, alloantigen and varicella-zoster virus antigen.
Blastogenesis of peripheral blood lymphocytes against IL-2, alloantigen and varicella-zoster virus antigen began to improve one month after transplantation, however it delayed in the recipients of unrelated marrow graft or CD34 enriched marrow graft. It also delayed in the patients complicated with graft-versus-host disease (GVHD) or severe viral infection.
II. In-vitro producion of cytokine by peripheral blood T-lymhocytes in patients with GVHD
Interferon-γ (IFN-γ) production by T-cells from patients with GVHD increased after stimulation by both interleukin-12 and immobilized anti-CD3 antibody, and elevated according to the grade of acute GVHD. In patients who received donor lymphocyte infusin (DLI), IFN-γ production increased after DLI, and decreased with the treatment of GVHD.
III. Analysis of Ebstein-Barr virus (EBV) genome of peripheral blood i
n bone marrow graft recipients
EBV genome in peripheral blood from the recipients of HLA-identical marrow, HLA-mismatched marrow, unrelated marrow and CD34-emiched marrow elevated ding one to twelve months after transplantation regardless of the kinds of donor or the methods of transplant. EBV-related B-cell lymphoproliferative disorder (EBV-BLPD) developed only among the recipients of CD34-enriched marrow cells. The amount of EBV genome in patients with EBV-BLPD was more than 10ィイD14ィエD1 copies.
IV. Induction of EBV-specific cytotoxic T-lymphocytes (EBV-CTLs)
The cultured EBV-CTLs did not react against autologous, non-EBV infected B-cells and allogeneic EBV-infected B-cells, but exhibit specific cytotoxicity against aoutologous EBV-infected B-cells. Infusion of EBV-CTLs into a patient of active EBV infection with 10ィイD15ィエD1 copies of EBV genome associated acute respiratory distress syndrome as a result of inflammation caused by the cytotoxicity of EBV-CTLs against EBV-infected pulmonary alveolar cells. However, EBV-BLPD did not developed in the patient. Less
Research Output (22results)