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1、惰性淋巴瘤规范化惰性淋巴瘤规范化治疗治疗0808年年NCCNNCCN治疗指南解读治疗指南解读 黄 慧 强中山大学附属肿瘤医院 淋巴瘤治疗研究中心Hungary ,Budapest 2008Hungary ,Budapest 20082008 2008 LuganoLugano ICML,InternationalICML,International Conference Conference MaglinantMaglinant LympphomaLympphomaWHO Lymphoma WHO Lymphoma ClassificationClassificationB cellB cel
2、l B cell chronic lymphocyticB cell chronic lymphocytic Mantle cellMantle cell Follicular lymphomaFollicular lymphoma Marginal B cell lymphoma, Marginal B cell lymphoma, MALT typeMALT type Plasma cell Plasma cell myeloma/plasmocytomamyeloma/plasmocytoma Diffuse large B cell lymphomaDiffuse large B ce
3、ll lymphoma BurkittsBurkitts lymphoma lymphoma Precursor B Precursor B lymphoblasticlymphoblastic leukemialeukemia/lymphoma/lymphomaT cellT cell Mycosis Mycosis fungoidesfungoides Peripheral T cell lymphoma, Peripheral T cell lymphoma, unspecifiedunspecified AngioimmunoblasticAngioimmunoblastic T ce
4、ll T cell lymphomalymphoma ExtranodalExtranodal NK/T cell lymphoma NK/T cell lymphoma Adult T cell Adult T cell leukemialeukemia/lymphoma /lymphoma (HTLV1+)(HTLV1+) AnaplasticAnaplastic large cell lymphoma, large cell lymphoma, primary systemicprimary systemic Precursor T cell Precursor T cell lymph
5、oblasticlymphoblastic leukemialeukemia/lymphoma/lymphomaDistribution of NHL subtypesDistribution of NHL subtypes In the UK In the UK (population 60m), (population 60m), there are 8,450 new there are 8,450 new NHL cases/yearNHL cases/year1 1 Across the EU Across the EU (population 490m) (population 4
6、90m) this equates to an this equates to an incidence of 69,000 incidence of 69,000 new NHL cases/yearnew NHL cases/yearALBCLOtherDLBCLFLMALT lymphomaMature T-cell lymphomaCLL/SLLMCLPMLBCL Burkitts lymphomaLiu Q, et al. Blood. 2003;102. Abstract 1446. Regimen生 存Treatment PeriodNo. of Patients5 yr (%)
7、10 yr (%)15 yr (%)CHOP BleoCHOP Bleo-IFNATT-IFNATT-IFN vs. FND-IFNFND-R vs. FND-R(+IFN)1977 19821982 19881988 19921992 19971997 2002961311361422006475828290375260-2942-IFN: interferon; ATT: alternating triple therapy with CHOD-B/ESHAP/NOPP; FND: fludarabine, mitoxantrone, and dexamethasone; Bleo: bl
8、eomycin; CHOP: cyclophosphamide, doxorubicin, vincristine, prednisoneYes, Survival Has Improved!Yes, Survival Has Improved!过去过去2525年惰性淋巴瘤的生存是否有改善年惰性淋巴瘤的生存是否有改善? ?Years%存活率0510152025020406080100CHOP-BleoCHOP-Bleo+IFNATTIFNATTIFN vs FNDIFNR-FND+IFN vs FNDR+IFNP LeukeranLeukeran 一线一线 - - 滤泡性淋巴瘤治疗滤泡性淋巴瘤
9、治疗: Randomized: RandomizedHiddemann Hiddemann et al.et al.CHOPCHOPR-CHOPR-CHOPp p可评估患者205223 反应率90%96%0.011 TTF31 mNot reached Ob1线FL4.Anton Hagenbeek (Holland)R- CHOP/ CHOP观 察q3m 8M: Ob 51.6 Vs 15 (m) R- CHOP/CHOP,CR M Ob, PFVFF) (FL)1线FL/M CL6.Martin DreylingFCM/R- FCM观 察q4m2R-m better (FL, MCL)R-
10、 matainence better1线FL/M CLIndolent NHL: induction and MaintenanceIndolent NHL: induction and Maintenanced8 after ASCTRituximab before and after ASCTRituximab before and after ASCT for relapsed aggressive B-NHLfor relapsed aggressive B-NHLCyclophosphamide Cyclophosphamide 47 g/m47 g/m2 2G-CSF G-CSF
11、10 g/kg/d10 g/kg/dBEAM /BEAM / ASCTASCTRituximab 1 g/m2Rituximab1 g/m2Rituximab 1 g/m2Rituximab 375 mg/m2d1d7d1 after ASCTKhouri IF, et al. J Clin Oncol 2005; 23:22402247.Historical comparisonN = 67Rituximab significantly improves outcomes Rituximab significantly improves outcomes when combined with
12、 HDT and ASCTwhen combined with HDT and ASCTKhouri IF, et al. J Clin Oncol 2005; 23:22402247.Overall survivalMonths post-transplant0.01.06309 12 15 18 21 24 27 30p = 0.004No rituximab (n = 30)Rituximab (n = 67)0.20.40.60.8Months post-transplant0.01.06309 12 15 18 21 24 27 30p = 0.0020.20.40.60.8Dise
13、ase-free survivalNo rituximab (n = 30)Rituximab (n = 67)Radio-Radio-ImmunoImmuno-Therapy -Therapy 单用单用有效率：有效率：RIT RIT 单用治疗复发耐药单用治疗复发耐药NHLNHLResponse Duration: Response Duration: RIT on relapsed or refractory NHLRIT on relapsed or refractory NHLCD20 -I 131:FL and Transformed NHL:CD20 -I 131:FL and Tr
14、ansformed NHL: Long term outcomeLong term outcome 11 studies ,1177 pts11 studies ,1177 pts M age 57 ( 21-90), stage 90%, tumor 5cm 47%,BM + 44%M age 57 ( 21-90), stage 90%, tumor 5cm 47%,BM + 44%1 1st st(141) 2rd (226) 3 (141) 2rd (226) 3rdrd (228) 4(228) 4thth ( 540)( 540) Response R. 95 73 58 46Response R. 95 73 58 46 M.d. response - 35 16 12M.d. response - 35 16 12 CR (%) 78 46 32 23CR (%) 78 46 32 23 M.d. CR - - 35 59M.d. CR - - 35 59 PFS1Y (%) 82 59
