急性gvhd的防治922.pptxVIP

急性GVHD的防治一般概念及发病机制影响因素诊断与鉴别诊断预防一线治疗及疗效判定二线治疗HLA配型与急性GVHD的发生100HLA-identical related1-Ag-mismatchedrelated802/3-Ag-mismatchedrelated% Grades 2-4 GVHD60HLA-matchedunrelated401-Ag-mismatchedunrelated200Adapted from Szydlo R, J Clin Oncol 1997HLA-identical SiblingCauses of Death after Transplants performed in2008-2009 （CIBMTR）New Malignancy (1%)Primary Disease (47%)GVHD (14%)Unrelated DonorInfection (12%)New Malignancy (1%)Primary Disease(33%)Organ Failure (4%)Other (21%)GVHD (15%)Infection (16%)Other (29%)OrganFailure (6%)SUM-WW11_17.pptGVHD发生的条件（Billingham，1966）移植物必须含有免疫活性细胞受者必须表达供者没有的组织相容性抗原(主要或次要)受者必须无力发动摧毁植入细胞的相关反应 GVHD的遗传学基础 主要组织相容性抗原（MHC） 次要组织相容性抗原 （MiHA）其它非HLA基因 KIR遗传多态性 细胞因子基因多态性 GVHD病理生理学的三个动因GVHD是供者淋巴细胞对所遇到的来自宿主的“异物”作出的正常反应，是一种过度的生理炎症反应在Allo-HSCT中，供者淋巴细胞被输入一个已有严重损害的宿主体内。基础疾病、移植前感染、预处理，均使内皮细胞、上皮细胞发生了炎症前改变GVHD的靶器官皮肤、肠道和肝脏（肺、骨髓、…）均广泛暴露在细菌内毒素和细胞炎性分子之中，这些物质可触发并放大局部炎症 急性GVHD病理生理学：三个阶段细胞因子网络失调学说组织损伤 宿主细胞分泌炎性因子抗原递呈 供者T细胞激活、增殖、分泌 ↓ “细胞因子风暴” ↑效应阶段 急性GVHD靶器官和组织损害Pathophysiology of acute graft-versus-host disease主要靶器官经典靶器官皮肤肝脏肠道其他靶器官？肺骨髓……Bone Marrow aGVHDGVHD Targets: Bone marrow?HSC, HPC?Cytokines?Niche?Osteoblastsvascular endothelial precucers Other ComplicationsSuppression of HematopoiesisCytopenia Delayed Immune recovery AnemiaSever infectionBleedingShono et al. Blood, 2010 115: 5401-5411aGVHD合并造血抑制者预后差重度aGVHD患者多出现一系、两系甚至全血细胞减少，对造血刺激因子治疗反应欠佳，治疗上依赖成分输血。 aGVHD是造血功能低下的主要危险因素，血小板减少是影响预后的因素之一。68.93%39.28%Non Relapse Mortality %35.62%32.43%36.5%11.25%42.6%27%Cytopenia(one lineage)No GVHDPancytopeniaGVHDBicytopeniaNon Relapse Mortality %Incidence % GVHD11.2%15.3%Cytopenia(one lineage)PancytopeniaBicytopenia LeukocytesPlateletsThe role of donor derived CD4 + and CD8 + cells in the development of cGVHDcGVHD in murine models is more donor T cell dose and survival time dependent HD donor CD4+ cells are more potent in induction of aGVHD, LD donor CD8+ T cells are more potent in induction of cGVHD Donor CD8+ cells in transplants are sufficient to induce aGVHD, the subsequent