儿童移植后因感染住院的人数在上升解析课件

儿童移植后因感染住院的人数在上升解析课件肾移植受体死亡原因肾移植受体死亡原因感染感染24%肿瘤肿瘤9%心血管疾病心血管疾病40%其他其他27%United States Renal Data System 1ST Kidney Transplants,1994-2000(N=67,874)肾移植受体死亡原因感染24%肿瘤9%心血管疾病40%其他27临床影响临床影响明显减少活体组织检查次数明显减少活体组织检查次数明显降低不良事故的发生率明显降低不良事故的发生率减少免疫抑制剂和抗生素的用量减少免疫抑制剂和抗生素的用量缩短住院病人的住院时间缩短住院病人的住院时间 减少出院病人的跟踪随访次数减少出院病人的跟踪随访次数Nazih Zuhdi Transplant Institute,Oklahoma City,OK临床影响明显减少活体组织检查次数Nazih Zuhdi Tr免疫抑制剂作用机制免疫抑制剂作用机制药物等级药物等级通用名称通用名称商标名称商标名称作用机制作用机制Calcineurin InhibitorsCyclosporin A,TacrolimusNeoral,PrografInhibit cytokine transcription of T-cellsTOR InhibitorsSirolimus,EverolimusRapamune,CerticanInhibits growth factor signal transduction of T-cellsAntimetabolitesAzathioprine,cyclophosphamide,mycophenolate mofetil,leflunomideImuran,Cytoxan,Cellcept,Rheumatrex,AravaInhibit Guanine nucleotide de novo synthesis affecting T-cellsCorticosteroidsPrednisone,methylpredinsolone,dexamethasoneOraone,Deltasone,Solumedrol,A-methaPred,Medrol,DecadronInhibits antigen presentation,cytokine production and proliferation of T-cellsPolyclonal and Monoclonal AntibodiesAnti-mature T-cells,anti-thymocytes,IL2 receptor antagonists,daclizumab,basiliximabOKT3,Thymoglobulin,Xenapax,SimulectProduce T-cell depletion,modulation of cell surface receptors,induction of anergy and apoptosis of activated T-cells免疫抑制剂作用机制药物等级通用名称商标名称作用机制Calci免疫机理免疫机理免疫机理Cylex 免疫细胞功能测定免疫细胞功能测定鉴定鉴定 移植患者的免疫状况移植患者的免疫状况/风险风险个体化个体化 免疫抑制反应更加精确化免疫抑制反应更加精确化监控监控 免疫抑制系统响应免疫抑制系统响应-治疗过程中的变化情况治疗过程中的变化情况提供提供临床不明显症状的研究临床不明显症状的研究最优化最优化 给药方案给药方案Cylex 免疫细胞功能测定鉴定 移植患者的免疫状况/风LuminometerATPATPATPATPATPATP细胞溶解释放细胞溶解释放 ATPATP 监测监测反应反应计算光照度计算光照度刺激淋巴细胞刺激淋巴细胞 w/PHA洗涤洗涤孵育孵育 15-18 hrs.磁力筛选磁力筛选 CD4细胞细胞.“In Vitro CMI:Rapid Assay for Measuring Cell-Mediated Immunity”,CRC Press,2002LuminometerATPATPATP细胞溶解释放 ATP临床试验临床试验取样有代表性-移植术后状况稳定的移植受体肾,肝&胰腺受体Clinical Transplantation:17:77-88,2003 临床试验取样有代表性-移植术后状况稳定的移植受体ClinicImmuKnow:不同人群的免疫响应不同人群的免疫响应Clinical Transplantation:17:77-88,2003 FDA 声明声明:ImmuKnow 监测服用免疫抑制剂人群的免疫细胞功能监测服用免疫抑制剂人群的免疫细胞功能强 低正常 健康成年人群健康成年人群 稳定的移植受体稳定的移植受体免疫响应免疫响应(ATP ng/mL)0200400600800415258(n=155)(n=127)P 2000次 ImmuKnow 测试肾,心,肝,小肠移植后大于3年的病人汇总分析汇总分析504 病人汇总分析不同类型移植受体免疫响应不同类型移植受体免疫响应强 低正常免疫响应免疫响应(ATP ng/mL)试验样本试验样本(n=127)肾肾(n=162)肝肝(n=107)心心(n=86)肺肺(n=128)小肠小肠(n=22)0200400600275258275236185228In Press-Transplantation不同类型移植受体免疫响应强 低正常免疫响应(ATP n免疫响应与临床结果相关免疫响应与临床结果相关正常人群正常人群稳定稳定排斥排斥感染感染免疫响应免疫响应(ATP ng/mL)02004006008001000415249488111强 低正常(n=155)(n=39)(n=504)(n=66)P 0.001P 96%In press-Transplantation移植受体病人统计数据病人统计数据 69移植受体临床情况如下移植受体临床情况如下:稳定稳定 51 人人排斥排斥 4 人人感染感染14 人人(9 CMV,2 parvovirus,1 plasma BK,1 late wound infection,1 recurrent UTI)The number of circulating CD4 cells following Campath-1H were significantly lower than pre-Tx levels.Pre-Tx846+4480-2 Months11+212-6 Months44+31 6 Months113+83Cylex assay was performed on 290 blood samples with a post-Tx follow-up from 2-18 months.病人统计数据 69移植受体临床情况如下:移植前免疫响应移植前免疫响应 移植后移植后12个月免疫状况个月免疫状况 SPK,PAK&PTA 受体受体 移植前移植前0-3M3-6M6-9M9-12M12M免疫响应免疫响应(ATP ng/mL)02004006008001000374270148195189159强 低正常移植前免疫响应 移植后12个月免疫状况 SPK,PT 细胞反应和不良事故之间有良好的相细胞反应和不良事故之间有良好的相关性关性移植前移植前 排斥排斥 稳定稳定 感染感染免疫响应免疫响应(ATP ng/mL)0200400600800100037455019448nsp 0.05p 0.001强 低正常N=4N=51N=14N=69T 细胞反应和不良事故之间有良好的相关性移植前 228 ng/mL ATP最小风险最小风险免疫响应免疫响应(ATP ng/mL)0100200300400500600相对风险相对风险02468101214排斥 感染最小风险水平 228 ng/mL ATPY=1.86相对风险分析相对风险分析228 ng/mL ATP最小风险免疫响应(ATP ng/BK 病毒感染与免疫功能低下是相关的病毒感染与免疫功能低下是相关的n=162n=290200400600稳定BK病毒感染免疫响应(ATP ng/mL)275146p 0.0001 强 低正常Data courtesy of NIDDK,INOVA,Rhode Island Hospital,Washington Hospital,UTMBBK 病毒感染与免疫功能低下是相关的n=162n=29020Multicenter:UCLA,JHU,NIDDK,UTMB,INOVA肾移植受体感染和排斥发生的几率对比肾移植受体感染和排斥发生的几率对比肾移植受体肾移植受体=162Multicenter:UCLA,JHU,NIDDK,ImmuKnow在管理治疗中的应用在管理治疗中的应用ImmuKnow在管理治疗中的应用不同移植受体出院之前主要使用诱导治疗方案不同移植受体出院之前主要使用诱导治疗方案不同移植受体出院之前主要使用诱导治疗方案不同免疫抑制剂在肾移植诱导治疗中应用不同免疫抑制剂在肾移植诱导治疗中应用不同免疫抑制剂在肾移植诱导治疗中应用Data courtesy of UCLA and UTMBrATG诱导治疗与免疫响应诱导治疗与免疫响应移植后天数移植后天数肌氨酸酐 e(mg/dL)免疫响应免疫响应(ATP ng/mL)024681012100200300400500600Tac/MMF/Prednisone0210714肌氨酸酐 ImmuKnow 移植后天数移植后天数rATG肌氨酸酐(mg/dL)123456免疫响应免疫响应(ATP ng/mL)2004006008001000Tac/MMF/Prednisone02107142ACR Day 37 响应响应 无响应无响应Data courtesy of UCLA and UTMBMeta-analysis:UCLA,UTMB,NIDDK,HAMrATG Induction ResponsivenessPre Induction Immune Response(ATP ng/mL)0200400600800%Change of Immune Response-1000100200300Pre Induction Immune Response(ATP ng/mL)02004006008000200400600800%Change of Immune Response-1000100200300-1000100200300RejectionNo RejectionRejectionN=52Non-ResponderResponderP 96%In press-TransplantationOddsThe Only FDA Cleared Immune Function TestSimple,Standardized and Reimbursable Blood TestEnables a Direct Measure of the Immune SystemIdentify Patients Immunological Status/RiskIndividualize Immunosuppressive Therapies Monitor Immune System Response to Therapy ChangesProvide Insight into Sub-Clinical Turning PointsOptimize Drug Levels to Achieve Lowest Dose ApproachThe Only FDA Cleared Immune Fu CustomersArkansas Childrens Hosp.Integris Baptist Med.Ctr.ViraCor LabsUniv.of Tennessee Johns Hopkins Univ.NIDDK/NIHCedars Sinai Hosp.Loma Linda Univ.Oklahoma Univ.UCLAQuest San Juan CapistranoSanta Rosa Hosp.Cleveland Clinic FoundationQuest ChantillyTexas Transplant Inst.Duke Univ.Quest HoustonRhode Island Hosp.Esoterix LabsTampa Gen./LifeLinkFairfax/Inova Hosp.Hahnemann Univ.Univ.of ArkansasMethodist-HoustonHosp.Auxillio Mutuo P.RicoUniv.of ColoradoSt.Lukes-Houston IBT LabsUniv.of MiamiUC San DiegoImmuno D LabsUT-HoustonSharp Mem.Hosp.SUNY DownstateUT-Southwest Washington Hosp.Ctr.Texas ChildrensUTMB-GalvestonAll Childrens Hosp.Arlington Cancer Ctr.Stanford Univ.Covenent Hosp.TXUniv.of Toronto Univ.of MinnesotaUHSC Texas Tech.Elliot Cancer Res.Ctr.Mayo ClinicKaiser Woodland HillsCentocorA.I.Dupont Hosp.Hershey Med.Ctr.U of Pittsburgh Med.Ctr.Pitt.County Mem.CustomersArkansas Childrens Patient:A 55 year old Hispanic Female Heart RecipientTherapy:Tacrolimus and PrednisoneHistory:Transition to SirolimusImmuKnow:Monitoring immune response during ISP changesTransition from Tacrolimus to SirolimusPatient:A 55 year old HispanTac/Pred decreaseRapa StartedDays Post Transplant250300350400450500Immune Response(ATP ng/mL)0200400600Tac/Rapa Levels(ng/mL)05101520ImmuKnowFK TDMRapa TDMData courtesy of Christus Santa Rosa Transplant InstituteTransition from Tacrolimus to SirolimusTac/Pred decreaseRapa StartedDPatient:A 58 year old Female Lung RecipientHistory:Problem with Diaphragm so can not biopsyImmuKnow:Monitoring immune response to adjust therapyManaging to Immunological StabilityPatient:A 58 year old FemaleDays Post Transplant0100200300400Immune Response(ATP ng/mL)0200400600ImmuKnow Data courtesy of Tampa General/LifelinkManaging to Immunological StabilityDays Post Transplant0100200300Patient:A 62 year old Female Liver Transplant RecipientTherapy:Tacrolimus and SirolimusHistory:HCV+ImmuKnow:Monitoring immune response to stabilityStability for HCV+Liver Transplant RecipientsPatient:A 62 year old FemaleManaging to Immunological StabilityRapa IncreasedDays Post Transplant 020406080100Immune Response(ATP ng/mL)0200400600Alt(IU/mL)02004006008001000ImmuKnow Alt Nazih Zuhdi Transplant Institute Manuscript in PreparationManaging to Immunological StabDays Post Transplant050100150200Immune Response(ATP ng/mL)02004006008001000FK TDM05101520EBV PCR0200040006000800010000120001400016000BX Proven PTLDCampathMMF 1000-500-d/cImmuKnow FK TDM EBV PCR LOWModerateHighCorrelation of low Immune Response with PTLDDays Post Transplant0501001502