霍奇金淋巴瘤的診治進(jìn)展.ppt

霍奇金淋巴瘤的診治進(jìn)展 四川大學(xué)華西醫(yī)院賈永前2011 3 19南寧 2010美國(guó)NCI發(fā)布的SEER前十大腫瘤 淋巴瘤骨髓瘤在世界的發(fā)病和死亡分布圖WHO2004 svg Blood2008 111 2997 2983 美國(guó)NCI1980 2004年SEER有關(guān)HL發(fā)病資料 霍奇金淋巴瘤的生物學(xué)特點(diǎn) HRS細(xì)胞及LP細(xì)胞起源于生發(fā)中心B淋巴細(xì)胞細(xì)胞標(biāo)記與B細(xì)胞有異同 CD20CD30 CD15 HRS細(xì)胞EBER 40 信號(hào)通路的異常 NF B的普遍過(guò)度表達(dá)新的藥物的試用 霍奇金淋巴瘤的治療策略 放射治療全淋巴次全淋巴區(qū)域淋巴受累區(qū)域 IFR 劑量503520cGr化學(xué)治療干細(xì)胞移植生物治療抗體CD20CD30表觀調(diào)控治療乙?；敢种苿?單純放療 聯(lián)合治療 Connors etal Vancouverexperience 2010NCCN有關(guān)HL治療指南 兩個(gè)療程化療后的IPS積分和PET CT評(píng)估結(jié)果 NCCN關(guān)于HL危險(xiǎn)度的建議 預(yù)后不良及晚期HL的治療策略 放射治療和聯(lián)合化療DFS80 特別是年輕患者 治療相關(guān)的晚期毒性 HL治療的挑戰(zhàn) 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會(huì)議 有關(guān)一些新的治療方案的探索 關(guān)于NLPHL的R CHOP治療 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放化療后的并發(fā)癥發(fā)生 Armitage NEnglJMed2010 363 653 62 ABVD方案的改良 華西經(jīng)驗(yàn) C ABVDG ABVD 2009年注冊(cè)方案 吉西他濱800mg m2 D1 15標(biāo)準(zhǔn)ABVD隨訪最長(zhǎng)3年 難治復(fù)發(fā)性HL的治療 大劑量化療 干細(xì)胞移植二線治療方案抗體及靶向治療吉西他濱的應(yīng)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 結(jié)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例可評(píng)價(jià)難治復(fù)發(fā)MCL DFLBCL HL用法 吉西他濱1g m2 qw 7周 間周1次 3次結(jié)果 CR1例 PR3例 SD3例 PD3例其中 HL1例療程第6周CR 持續(xù)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