霍奇金淋巴瘤的诊治进展.ppt

霍奇金淋巴瘤的诊治进展 四川大学华西医院贾永前2011 3 19南宁 2010美国NCI发布的SEER前十大肿瘤 淋巴瘤骨髓瘤在世界的发病和死亡分布图WHO2004 svg Blood2008 111 2997 2983 美国NCI1980 2004年SEER有关HL发病资料 霍奇金淋巴瘤的生物学特点 HRS细胞及LP细胞起源于生发中心B淋巴细胞细胞标记与B细胞有异同 CD20CD30 CD15 HRS细胞EBER 40 信号通路的异常 NF B的普遍过度表达新的药物的试用 霍奇金淋巴瘤的治疗策略 放射治疗全淋巴次全淋巴区域淋巴受累区域 IFR 剂量503520cGr化学治疗干细胞移植生物治疗抗体CD20CD30表观调控治疗乙酰化酶抑制剂 单纯放疗 联合治疗 Connors etal Vancouverexperience 2010NCCN有关HL治疗指南 两个疗程化疗后的IPS积分和PET CT评估结果 NCCN关于HL危险度的建议 预后不良及晚期HL的治疗策略 放射治疗和联合化疗DFS80 特别是年轻患者 治疗相关的晚期毒性 HL治疗的挑战 治愈率VS毒性 Developedinthemid1960sNCIVincentDeVitaetalofhistoricalimportance MOPPregimen Mechlorethamine 6mg m2 days1and8Vincristine 1 4mg m2 days1and8Procarbazine 100mg m2 days1 14Prednisone 40mg m2 days1 14 cycles1and4only MOPPregimen MOPP COPPCOPP ABDABVDABVD intheearly1970sGianniBonadonnaandhiscolleagues ABVDissuperiortoMOPPintermsofDFSandhasalowerincidenceofsterilityandsecondaryleukemia StandardchemotherapyregimenforHodgkin slymphoma ABVDregimen Every28daysfor6ormorecycles Adriamycin 25mg m2 days1 15Bleomycin 10mg m2 days1 15Vinblastine 6mg m2 days1 15Dacarbazine 375mg m2 days1 15 ABVDregimen ABVD StanfordVMOPPEBVCADVAPEC BChlVPP EVABEACOPP escalated TheBEACOPPregimenwasdevelopedinGermanyVolkerDiehlandcolleaguesbeusefulforunfavorable advanced stageHodgkin slymphomaHowever escalatedBEACOPPisassociatedwithgreaterhematologictoxicityandahigherincidenceofsecondarymalignancies Bleomycin 10mg m2 day8Etoposide 200mg m2 days1 3Doxorubicin 35mg m2 day1Cyclophosphamide 1 250mg m2 day1Vincristine 1 4mg m2 day8Procarbazine 100mg m2 days1 7Prednisone 40mg m2 days1 14 EscalatedBEACOPPregimen MEC MOPP EBV CAD ASH2010会议 有关一些新的治疗方案的探索 关于NLPHL的R CHOP治疗 M D AndersonCancerCenter83例 Blood ASHAnnualMeetingAbstracts 2010116 Abstract2812 E2496 ABVDvsStanfordV RadiationTherapyinAdvancedHodgkinLymphoma Primaryendpoint failure freesurvival GordonLI etal ASH2010 Abstract415 ABVD6 8cyclesmodifiedIFRT36Gyonlyinpatientswithmassivemediastinaldisease n 404 StanfordV12wks chemotherapy modifiedIFRT36Gytosites 5cminmaxtransversedimension n 408 Definedasmass 1 3maximumintrathoracicdiameteronstandingPAchestx ray PreviouslyuntreatedpatientswithhistologicallyprovenHL advancedorlocallyextensivedisease massivemediastinaladenopathy N 812 E2496 Results ABVDremainsstandardofcare5 yrFFS higherforABVDSimilarratesoftoxicitybetweentreatmentarmsHigherratesofgrade3lymphopenia P 0001 andgrade3sensoryneuropathy P 001 withStanfordV P notsignificant GordonLI etal ASH2010 Abstract415 GHSGHD14 BEACOPPvsABVDinEarlyUnfavorableHodgkin sLymphoma ArmAclosedon10 07 08Primaryobjective freedomfromtreatmentfailure EngertA etal ASH2010 Abstract765 ArmAABVDfor4cycles n 818 ArmBEscalatedBEACOPPfor2cycles ABVDfor2cycles n 805 Patientsaged16 60yrswithhistologicallyconfirmedCSI IIAdiseaseandoneofthefollowing extranodaldisease elevatedESR largemediastinalmass 3LN areas N 1655 30GyIFRT 30GYIFRT GHSGHD14 Results ITTPopulation FFTF PFS Medianobservationtime 42mos EngertA etal ASH2010 Abstract765 1 0 ProportionofPatientsWithFFTF 0 9 0 8 0 7 0 6 0 5 0 4 0 3 0 2 0 1 0 0 12 24 36 48 60 Mos PtsatRisk n 818 749 629 459 299 148 805 733 624 479 307 174 A B P 0001 A HR 0 49 95 CI0 34 0 72 B 770 761 702 700 533 541 374 381 231 243 5 YrFFTF 95 CI 87 6 94 3 84 8 90 4 92 5 96 1 ArmAArmB 1 0 ProportionofPatientsWithPFS 0 9 0 8 0 7 0 6 0 5 0 4 0 3 0 2 0 1 0 0 12 24 36 48 60 Mos PtsatRisk n 818 773 647 474 308 154 805 757 646 492 313 177 A B BEACOPP P 0002 A ABVD HR 0 47 95 CI 0 31 0 71 B 803 790 724 722 584 559 387 391 240 247 5 YrPFS 95 CI 89 3 95 3 86 7 92 0 93 6 97 0 ArmAArmB BEACOPP ABVD 早期HL放化疗后的并发症发生 Armitage NEnglJMed2010 363 653 62 ABVD方案的改良 华西经验 C ABVDG ABVD 2009年注册方案 吉西他滨800mg m2 D1 15标准ABVD随访最长3年 难治复发性HL的治疗 大剂量化疗 干细胞移植二线治疗方案抗体及靶向治疗吉西他滨的应用 High DoseCyclophosphamide Cy Rituximab andaCancerVaccineforRelapsedClassicalHodgkin sLymphoma cHL YvetteL Kasamon etal JohnsHopkinsUniversity rituximab375mg m2IVond1and4Cy 50mg kg dIVond8 11 withmesna filgrastimrituximab375mg m2IVweeklyfor4weeksuponplateletrecoveryHLvaccine 1x10exp8cells dose wasadministered1dafterCycompletionand4 8 12 16 and24weekslater Blood ASHAnnualMeetingAbstracts 2010116 Abstract3954 结果 22ptshadCRorPR2hadstabledisease1haduntestedrelapse GemBuMelIsaNewHDCRegimenwithHighActivityInRefractoryHodgkin sLymphoma HL PatientsReceivingAnAutologousStem CellTransplant ASCT AContemporaneousComparisonwithBEAMandBusulfan Melphalan BuMel MDAnderson Buwasgivenas4dailydosesondays 8to 5targetinganAUCof4 000 dMelwasgivenat60mg m2 dond 3andd 2Gemwasinfusedover3hoursatafixeddoserateof10mg m2 min totaldose1875mg m2 ondays 8and 3 Blood ASHAnnualMeetingAbstracts 2010116 Abstract690 Blood ASHAnnualMeetingAbstracts 2010116 Abstract690 病例 15例13例可评价难治复发MCL DFLBCL HL用法 吉西他滨1g m2 qw 7周 间周1次 3次结果 CR1例 PR3例 SD3例 PD3例其中 HL1例疗程第6周CR 持续21月 GemcitabineintheTreatmentofRefractoryHodgkin sDisease ResultsofaMulticenterPhaseIIStudyByA Santoro H Bredenfeld L Devizzi H Tesch V Bonfante S Viviani F Fiedler H SotoParra C Benoehr M Pacini G Bonadonna V DiehlCONCLUSION Responserate39 Drug relatedtoxicitiesweremildGemcitabinewasshowntobeactiveinheavilypretreatedpatientswithHodgkin sdisease JClinOncol18 2615 2619 Phase2StudyofGemcitabineinCombinationWithRituximabinPatientsWithRecurrentorRefractoryHodgkinLymphoma Gemcitabine1250mg m2Day1 8病例33例有效率48 CR或CRu15 PR33 Cancer2008 112 831 6 GDPisanactiveandnon toxicchemotherapyregimeninrelapsedorrefractoryHodgkin sdisease aphaseIIstudybytheNationalCancerInstituteofCanadaClinicalTrialsGroup GDP方案CR17 3 PR52