| Project/Area Number |
15390309
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
MORISHIMA Yasuo Aichi Cancer Center Research Institute, Immunology, Researcher, 腫瘍免疫学部, 研究員 (20220056)
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| Co-Investigator(Kenkyū-buntansha) |
田地 浩史 愛知県がんセンター(研究所), 腫瘍免疫学部, 研究員
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | allogeneic bone marrow transplantation / GVL effect / GVHD / HLA / 移植片対腫瘍効果 / 移植片対宿主病 / 移植片対白血病効果 / 造血幹細胞移植 / KIR / HLA-C |
|---|
| Research Abstract |
To elucidate the responsible HLA locus at the allele level and the role of killer immunoglobulin-like receptor (KIR) in the clinical outcome in unrelated hematopoietic stem cell transplantation (UR-HSCT), 2423 patients transplanted with T cell-replete marrow through the Japan Marrow Donor Program (JMDP) were registered consecutively. Multivariate analysis demonstrated that not only the mismatch of HLA-A,-B,-C and-DPB1 but also KIR2DL ligand mismatch in GVH vector (KIR-L-MM) increased the rate of acute GVHD. HLA-C mismatch in acute lymphoblastic leukemia (ALL) and HLA-DPB1 mismatch in chronic myelocytic leukemia reduced the leukemia relapse rate significantly. In contrast, KIR-L-MM induced a higher relapse rate than match, which was especially remarkable in ALL. The risk factors for mortality were HLA-A,-B,-C,-DQB1 and KIR-L-MM. Patient lack of KIR2DL and KIR3DL1 ligands showed a marginal effect in inducing acute GVHD and higher mortality, but no effect on leukemia relapse. JMDP analysis with a large-scale homogeneous cohort provided important messages for transplant immunology and the selection of unrelated donor. First, HLA-C and HLA-DPB1 induced anti-leukemic effect, which should be considered based on leukemia cell type. Second, KIR-L-MM induced adverse effects on transplant outcome and brought no benefit for patients with T cell-replete UR-HSCT.
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