成人急性淋巴细胞白血病的治疗课件.ppt

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1、成人急性淋巴细胞白血病的治疗第1页，此课件共22页哦ALL化学治疗诱导治疗诱导治疗自发缓解VCR+Pred（VP）诱导，CR 36 67%VCR+DNR+Pred（VDP）诱导，CR 70 85%VCR+DNR+L-Asp+Pred（VDLP）缓解期延长VCR+DNR+CTX+Pred（VDCP）缓解后治疗缓解后治疗T-ALL：大剂量CTX冲击+Ara-C成熟B-ALL：短疗程诱导及强化治疗中枢系统白血病的预防及治疗中枢系统白血病的预防及治疗第2页，此课件共22页哦Remission Induction Regimens And Postremission Therapy for ALL No

2、.of CNS Survival Reference patients Induction Consolidation Maintenance Prophylaxis CR%Med(mo)Blood 368 V,P,D,Cy,Dex,V,Dox,Cy 6-MP,MTX MTX,XRT 74 2871:123,1988 Ara-c,6-MP Ara-C,TGBlood 168 V,P,Dox,Cy Ara-C,MTX,TG V,P,Dox,6-MP MTX 68 18 73:87,1989 V,P,A,Cy MTX,ActD,Cy BCNUBlood 109 V,P,A,D V,P,A,D 6-

3、MP,MTX MTX,XRT 88 28 78:2814,1991 Ara-c,VM26,MTX Leukemia 541 V,P,D,A V,P,Mito;6-MP,MTX MTX 80 NR 6:182,1992 Cy V,Dex,MTX;VM26,Ara-CBlood 197 V,P,A,D,Cy Cy,Ara-c,6-MP,V 6-MP,MTX MTX,XRT 85 3685:78:2814,1995 A,Dox,Dex,TG V,P Blood 128 Cy,V,Dox,Dex MTX,Ara-C 6-MP,MTX,V,P MTX,Ara-C 91 36 86:173a,1995 第

4、3页，此课件共22页哦Group Year n(pts)Age*Induction Consolidation Maintenance CR LFSStudies with 500 patientsGMALL 02/84 1993 562 28 V,P,A,D,C,AC,M,MP V,DX,AD,AC,C,TG,VM MP,M 75%39%at7yFGTALL 1993 581 33 V,P,D/R,C AD,AC AD,AC,A MP,M,V,C,P,AD,AC 76%30%at10yMRC-UKALL XA 3 1997 618 15 V,P,A,D AC,VP,D,TG MP,M,V,P

5、 82%28%at5yMRC/ECOG 4 1999 920 V,P,D,A,C,AC,MP HDM,A AC,VP,V,DX,MP,M,V,P 89%D,C,TG SCT GMALL 05/93 5 2001 1163 35 V,P,A,D,C,AC,M,MP V,DX,AD,AC,C,TG,VM,MP,M 83%AC,HDM,A,CHDAC,MiGIMEMA 0288 6 2002 794 28 V,P,A,D,C,HDAC,Mi V,HDM,HDAC,DX,VM MP,M,V,AC,Mi,VM,82%29%at9y HDAC,HDM,DXTotal 4638 82%31%(%=weigh

6、ted mean)Results of adult acute lymphoblastic leukemia(ALL)studies(1)Dieter Hoelzer,et al,Hematology,2002 164-191第4页，此课件共22页哦Results of adult acute lymphoblastic leukemia(ALL)studies(2)Group Year n(pts)Age*Induction Consolidation Maintenance CR LFSRecent Studies with 100 patientsPethema ALL-93 7 199

7、8 108 28 V,P,D,A,C HDM,V,D,P,A,C,VM,AC MP,M V,P,Mi,86%41%at4y A,C,VM,ACCALGB 8 1998 198 35 V,P,D,A,C C,MP,AC,V,A,M,AD,DX,TG,P MP,M,V,P 85%36%at3ySweden 9 1999 120 44 HDAC,C,D,V,BX AD,HDAC,V,BX,C,D,n.r.85%36%at3y VP SCTMDACC 10 2000 204 39 V,AD,DX,C HDM,HDAC,C,P MP,M,V,P 91%38%at 5y Lombardia 11 2001

8、 121 35 I,V,A,P,C I,V,C,VM,HDAC,HDM,MP,M 84%49%at3y DX SCTNetherlands 12 2001 193 33 Standard HDAC,VP16+allo/auto SC 82%35%at 5yTotal 944 86%38%(%=weighted mean)Dieter Hoelzer,et al,Hematology,2002 164-191第5页，此课件共22页哦Cancer and Leukemia Group B(CALGB)Study 8811(1)Course I:Induction(4 wk)CTXIV1200 mg

9、/m2Day 1DNRIV45 mg/m2Days 1,2,3VCRIV2 mgDays 1,8,15,22PredPO60 mg/m2Days 1-21L-AspSC6000 IU/m2Days 5,8,11,15,18,22For patients 60 yr oldCTX800mg/m2Days 1DNR30mg/m2Days 1,2,3Pred60mg/m2Days 1-7Larson RA,et al,Blood,85:2025-2037第6页，此课件共22页哦CALGB 8811（2）Course II:Early intensification(4 wk,repeat once)

10、MTXIT15 mgDay 1CTXIV1000 mg/m2Day 16-MPPO60 mg/m2/dDays 1-14Ara-C SC75 mg/m2/dDays 1-4,8-11VCRIV2 mgDays 15,22L-Asp SC6000 IU/m2Days 15,18,22,25Course III:CNS prophylaxis and interim maintenance(12 wk)Cranial irradiation2400 cGyDays 1-12MTXIT15 mgDays 1,8,15,22,296-MPPO60 mg/m2/dDays 1-70MTXPO20 mg/

11、m2Days 36,43,50,57,64 第7页，此课件共22页哦CALGB 8811(3)Course IV:Late intensification(8 wk)ADRIV30 mg/m2Days 1,8,15VCRIV2 mgDays 1,8,15DEXPO10 mg/m2/dDays 1-14CTXIV1000 mg/m2/dDay 296-TGPO60 mg/m2/dDays 29-42Ara-CSC75 mg/m2/dDays 29-32,36-39Course V:Prolonged maintenance(until 24 mo from diagnosis)VCRIV2 mg

12、Day 1 of every 4 wkPredPO60 mg/m2/dDays 1-5 of every 4 wkMTXPO20 mg/m2Days 1,8,15,226-MPPO60 mg/m2/dDays 1-28第8页，此课件共22页哦CALGB 8811(4)Results of TherapyPatients214Patients eligible197Induction death17(9%)Refractory disease13(7%)CR167(85%)Died in remission10(6%)Censored for BMT in 1st CR5(3%)Relapsed

13、77(46%)CCR75(45%)第9页，此课件共22页哦CALGB 8811(5)Results of therapy Remission Duration Survival CR Median Probability of CCR Median Probability of Survival Variable n(%)n(%)p (mo)at 3 yr(95%CI)p (mo)at 3 yr (95%)p Total 197 165(85)29 0.46(0.37-0.55)36 0.50(0.42-0.50)CR 167 45Age(yr)30 87(44)82(94)0.01 36 0

14、.51(0.38-0.63)0.21 42 0.69(0.57-0.68)0.0130-59 92(47)78(85)25 0.43(0.39-0.57)25 0.39(0.28-0.51)60 18(9)7(39)12 0.43(0.16-0.75)1 0.17(0.06-0.39)Leucocytes30,000 130(66)115(88)0.06 37 0.51(0.40-0.62)0.05 44 0.59(0.49-0.68)0.001 30,000 66(34)51(77)19 0.36(0.22-0.53)19 0.34(0.23-0.47)FABL1 71(37)64(90)0

15、.35 38 0.54(0.39-0.68)0.16 44 0.63(0.50-0.74)0.03L2 87(46)73(84)26 0.46(0.33-0.59)25 0.45(0.34-0.57)L3 8(4)6(75)3 0.17(0.03-0.56)6 0.38(0.11-0.74)第10页，此课件共22页哦CALGB 8811(6)Results of therapy Remission Duration Survival CR Median Probability of CCR Median Probability of Survival Variable n(%)n(%)p (m

16、o)at 3 yr(95%CI)p (mo)at 3 yr (95%)p Immunophenotypes B 67(48)55(82)0.02 25 0.42(0.27-0.58)0.14 19 0.36(0.25-0.49)0.004T 31(22)31(100)28 0.57(0.37-0.76)40 0.67(0.47-0.82)BMy 19(14)14(74)27 0.38(0.18-0.64)27 0.47(0.26-0.69)TMy 8(6)7(88)40 0.86(0.49-0.97)40 0.75(0.41-0.93)Other 15(11)13(87)31 0.53(0.2

17、8-0.76)43 0.60(0.36-0.80)B+BMy 86(61)69(80)0.01 25 0.41(0.28-0.55)21 0.38(0.28-0.50)0.001T+TMy 39(28)38(97)32 0.63(0.44-0.78)40 0.69(0.51-0.82)Cytogenetics and MolecularPh+or BCR-ABL+30 21(70)0.11 7 0.11(0.04-0.28)11 0.16(0.07-0.32)0.001Negative by 1 test 83 70(84)33 0.56(0.43-0.69)44 0.45(0.45-0.67

18、)Negative by both test 29 25(86)40 0.72(0.51-0.86)40 0.62(0.44-0.78)第11页，此课件共22页哦Treatment Results in Adult Burkitt-type L3 ALLReference N Induction Continuation CR(%)LFS(%)SFOP 17 C,V,P,Dox V,P 76 58Baillieres Clin Oncol MTX 3-8g MTX 8g 7:339,1994 CTX 0.5-1g Ara-C 3gMDACC 13 V,Dox,Dex MTX 1g 85 46P

19、roc ASCO,14:339,1995 Ara-C 1.8g Ara-C 3g GMALL 24 C,Ara-C,VM,P C,Ara-C,P 63 50 Blood,87:495,1996 MTX 0.5g MTX 0.5g 35 V,Ifo,VM,Ara-C V,C,Ara-C,Dex 74 71 Dex,MTX 1.5g MTX 1.5gCALGB 24 V,Ifo,VP,Ara-C C,V,Dox,Ara-C 75 66Proc ASCO,16:24a,1997 Dex,MTX 1.5g MTX 1.5g 第12页，此课件共22页哦ABAABBPCNS Irrd20468101214

20、1618weeksB-NHL-86 protocol for B-cell ALL第13页，此课件共22页哦Treatment of B-cell ALLB-NHL 86 protocolPretreatment WBC 25,000/l,or large tumor mass Pred 60 mg/m2,PO 5 days CTX 200 mg/m2,IV To avoid tumor lysis syndrome and correct possible metabolic disturbanceCycle A Given at week 1,7,13 MTX 15 mg,Ara-C 40

21、 mg,Dex 4 mg,IT,day 1 VCR 2 mg,IV,day 1 MTX 1500 mg/m2,24h INF,day 1 IFO 800 mg/m2,IV,days 1 5,VM26 100 mg/m2,days 4,5 Ara-C 150 mg/m2/q12h,IV,days 4,5 Dex 10 mg/m2,PO,days 1-5 Hoelzer D,et al,Blood,87:495,1996第14页，此课件共22页哦Cycle BGiven at week 4,10,16 MTX 15 mg,Ara-C 40 mg,Dex 4 mg,IT,day 1 VCR 2 mg

22、,IV,day 1 MTX 1500 mg/m2,24h INF,day 1 CTX 200 mg/m2,IV,days 1 5,ADR 25 mg/m2,days 4,5 Dex 10 mg/m2,PO,days 1 5CNS Prophylaxis and Treatment MTX,Ara-C,Dex triple intrathecal therapy Irradiation 24 Gy,given weeks 5-7 without CNS involvement,cranial irradiation with CNS involvement,cranial and spinal

23、irradiation第15页，此课件共22页哦Risk Groups in precursor-B and T-lineage ALLGood Risk:both B and T-lineage ALL with all of the following features No adverse cytogenetic abnormalities Age 30 years WBC count at presentation 30,000/L Achieve CR in 4 6 weeksIntermediate Risk:ALL with prognosis features of neith

24、er good nor poor risk groupPoor Risk:ALL with any of the following prognosis features:Age 60 years Precursor-B with WBC count 30,000/l Adverse Cytogenetics-t(9;22),t(4:11),or trisomy 8 Achievment of late CR,4-6 weeks post induction 第16页，此课件共22页哦高危成人高危成人ALL的治疗的治疗t(4;11)ALL 发生率：儿童ALL 2 5%，婴儿42-66%，成人

25、3 6%；免疫表型：主要为早期B前体细胞（前前B），HLA-DR,CD19,CD22,CD79a 阳性，CD10阴性。59%患者共表达髓系抗原CD15和 CDw65。临床特点：女性多见（60%），高白细胞，预后差，儿童LES仅为9-19%，成人缓解期小于1年。治疗要点：早期强化，Ara-C 3 g/m2,days 1 4,Mito 10 mg/m2,days 2 6；CR1期异基因骨髓移植，两者LFS分别为48%、60%。t(9;22)ALL 化疗CR率不低，但缓解期短，应尽早行Allo-BMT Schoch C,et al,Ann hematol,70:195,1995第17页，此课件共22

26、页哦 CNS白血病白血病 初诊时CNS白血病发生率(%)成人ALL 6 T-cell ALL 8 成熟B-cell ALL 13 CNS白血病复发率（%）无预防治疗 30（29 32）鞘注化疗 13（8 19）颅脑照射 24 Gy 9（3 19）大剂量化疗 14（10 16）大剂量化疗+鞘注 7（2 16）大剂量化疗+鞘注+颅脑照射 6（1 13）第18页，此课件共22页哦Salvage regimens in relapsed or refractory adult ALL MedianStudy Therapy N CR(%)CR/Survival(mos)A.Vincristine-st

27、eroid-anthracyclinesCancer Treat Rep,63:1413,1979 V,Dox,Pred 10 40 7/-J Clin Oncol,8:994,1990 V,Dox,Dex 64 39 6.5/5.3Leukemia,11:2039,1997 V,Dox,Dex,CTX 66 44 12/8Br J Hematol,97:86,1997 V,IDA,Pred,BMT 61 56 2/-B.MTX-ASPCancer,43:1089,1979 Asp,MTX 12 33 7/-Blood,59:334,1982 MTX,V,Asp,Dex 14 79 7.5/1

28、1.2Am J Hematol,4:173,1978 V,P,Dox,Asp 23 69 4/7Cancer Treat Rep,65:83,1981 Asp,MTX 26 58 4/-Asp,MTX,Ifo 11 55 3.3/-第19页，此课件共22页哦Salvage Regimens in Relapsed or Refractory adult ALL MedianStudy Therapy N CR(%)CR/Survival(mos)C.High-dose Ara-C(HDAC)Am J Med,81:387,1986 HDAC 21 38 2/3.5Leukemia,4:637,

29、1990 Mito+HDAC 24 50 3.5/-Cancer,65:5,1990 Mito+HDAC 21 38 2/3.5Blood,72:433,1988 Amsa+HDAC 40 72 4/-Cancer,72:2155,1993 Flud+HDAC 30 30 5.5/3Leuk Lymph,25:579,1997 Flud+Ara-C+G-CSF 12 83 -/-Proc ASCO,6:147,1987 HDAC 16 50 6/-第20页，此课件共22页哦成 人 ALL HSCT 治疗 在过去的10年里，成人ALL的治疗取得了显著的进步，较大的多中心研 究中CR率75%-89

30、%,LFS28%-39%。在ALL预后良好亚型的治疗上取得了较 大的进步，如T-ALL或成熟B-ALL,LFS50%。而Ph/BCR-ABL阳性ALL的 LFS20%。预后因素用于危险分层，并根据其亚组分型和复发危险进行 个体化治疗至关重要。HSCT可以使高危或复发或未缓解的病人获得延长的LDF。5第21页，此课件共22页哦1.1 ALL in First remission通过衡量移植相关死亡率与单独标准化疗的治愈率，通过衡量移植相关死亡率与单独标准化疗的治愈率，allo-HSCT作为诱导后治疗对标准化疗后的高危复发病人是有作为诱导后治疗对标准化疗后的高危复发病人是有利的利的 Study N

31、 DFS with allogeneic HSCT(%)DFS with autograft or chemo (%)P ValueHovon18(56)124 53 36 0.05UKALL (Ph-)(57)434 54 34 0.04UKALL (Ph+)(58)148 41 a 27 a 0.5LALA87(9)257 46 a 31 a 0.04IBMTR(59)719 34 32 NSJapanese Study(60)290 53 b 30 b 0.02BGMT 120 68 26 0.01 Comparative studies of Allogeneic HSCT in adults(15 yrs.)with ALL in first CR a Overall survival.，b Age30.第22页，此课件共22页哦