儿童非霍奇金淋巴瘤诊疗建议课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,儿童非霍奇金淋巴瘤诊疗建议课件,*,儿童非霍奇金淋巴瘤诊疗建议（2004讨论稿）,中华医学会儿科分会血液组,中华儿科杂志,上海儿童医学中心 汤静燕起草,儿童非霍奇金淋巴瘤诊疗建议课件,背 景,王耀平教授执笔了第一个儿童淋巴瘤诊疗建议，至今已10年余。,国际上儿童淋巴瘤的总体的5年无病生存率已达70%以上。,我国仍相对落后，诊断和治疗水平相差较大。,儿童非霍奇金淋巴瘤诊疗建议课件,NHL Protocol Review,儿童非霍奇金淋巴瘤诊疗建议课件,NHL-BFM90 Report (T-LBL)Blood ,2000,95(2):416,0-18,y, T-cell, F:M 24:81.,106 patients, I:2, II:2, III:82, IV:19. BM(+) 15, CNS(+) 3.,Protocol:,ALL-like protocol.,Induction: CTX 1g/m, d36,64.Re-in d36,HDMTX 5.0g/m/24h X 4.,Asp X 2（10000/M x 8，x4）,CRT：1200 cGy for III/IV,Total CTX 3g, Adr 240mg/m.,Total therapy 2 y.,儿童非霍奇金淋巴瘤诊疗建议课件,Result,5y EFS 90%,No different at,Sex, age,LDH(500),III or IV,immunotyping,d33 CR or not,儿童非霍奇金淋巴瘤诊疗建议课件,POG 8704 Report-T-ALLand T-NHL,Leukemia 1999;13:335,T-ALL 357caes, T-NHL(lymphoblastic) 195,whole protocol basicly like ALL,After CR:,High dose Asp 25000/m/w x 20W from d 99 as consolidation,No high dose Asp consolidation,儿童非霍奇金淋巴瘤诊疗建议课件,4,y EFS ALL: 68% vs 55%,NHL: 78% vs 64%,儿童非霍奇金淋巴瘤诊疗建议课件,BFM 90 B-cell Report,Blood 1999;94:3294,Object:,LDH and early response,For group III and LDH 500 , MTX from 0.5 to 5.0,2 cycles for complete resected disease,systemic chemo plus intravencular therapy for CNS positive patiens,儿童非霍奇金淋巴瘤诊疗建议课件,Grouping,R1:,CR,R2:,no-abdomen primary or incompletely resect,LDH 500,or multiple bone,BM,CNS involvement,6 cycles,No-CR after 2 cycles: HDAra-c+Vp-16 for 2 cycles If CR, plus another 3 cycles,儿童非霍奇金淋巴瘤诊疗建议课件,Protocol B-Cell-BFM-90,R1 V-A - B,R2 V-AA-BB-CR-AA-BB,R3 V-AA-BB-CR-AA-BB-AA-BB,PR-CC-CR-AA-BB-CC,PR,OP-Negtive,Positive-ABMT,儿童非霍奇金淋巴瘤诊疗建议课件,V,1 2 3 4 5,Pred 30mg/m/d x x x x x,CTX 200mg/m/1h x x x x x,I/T x,儿童非霍奇金淋巴瘤诊疗建议课件,A 1 2 3 4 5,DX 10mg/m/d x x x x x,Ifos 800mg/m/d/1h x x x x x,MTX 500mg/m/24h* x,IT x,Ara-c 150mg/m/q12h/1h xx xx,Vp-16 100mg/m/1h x x,*CF 12mg/m 48,54h,10%MTX/30,90%23.5h,儿童非霍奇金淋巴瘤诊疗建议课件,B,1 2 3 4 5,Dx 10mg/m x x x x x,CTX 200mg/m/1h x x x x x,MTX 500mg/m/24h x,IT x,Adr 25mg/m/1h x,儿童非霍奇金淋巴瘤诊疗建议课件,AA,1 2 3 4 5,Dx 10mg/m x x x x x,Ifos 800mg/m/1h x x x x x,MTX 5g/m/24h* x,IT x,VcR 1.5mg/m x,Ara-C 150mg/m/1h/q12h xx xx,Vp-16 100mg/m/d/1h x x,儿童非霍奇金淋巴瘤诊疗建议课件,*,CF 30mg 42,48h, q6h ajusted as follows:,1-2umol/L 30mg/m,2-3umol/L 45mg/m,3-4umol/L 60mg/m,4-5umol/l 75mg/m,5umol/L: CFmg=MTXumol/L/kg,MTX 10%30, 90%23.5h,儿童非霍奇金淋巴瘤诊疗建议课件,BB,1 2 3 4 5,Dx 10mg/m x x x x x,CTX 200mg/m/1h x x x x x,MTX 5.0g/24h x,IT x,Adr 25mg/m/1h x,儿童非霍奇金淋巴瘤诊疗建议课件,CC,1 2 3 4 5,Dx 20mg/m x x x x x,VDS 3mg/m(max 5mg) x,Ara-C 2.0g/m/3h xx xx,Vp-16 150mg/m/1h x x x,IT x,儿童非霍奇金淋巴瘤诊疗建议课件,CNS(+) Intraventricularly Chemo,AA and BB,MTX 3mg, Pred 2.5mg d1,2,3,4,Ara-C 30mg d5,CC,MTX 3mg, Pred 2.5mg d3,4,5,6,Ara-C 30mg d7,儿童非霍奇金淋巴瘤诊疗建议课件,ABMT Pre-conditioning,-8 -7 -6 -5 -4 -3 -2 -1 0,Busulfan 120mg/m* ! ! ! !,VP-16 300mg/m/4h ! ! !,CTX 1.5g/m/1h# ! ! !,Stem cell transfusion !,* Divided p.o,# If CNS(+) thiotepa 300mg/m/d x 3 replace of CTX,儿童非霍奇金淋巴瘤诊疗建议课件,Result and Conclusion,R1:100%, R2: 96%, R3 78%.,HDMTX effective in R2 and R3,Stage III, LDH500u/L, PEFS 81%, control 43%. 6y EFS,ABMT(residual after 3 cycles) effective, 5/6 survived, control: 4/5 progress.,儿童非霍奇金淋巴瘤诊疗建议课件,Confirmed the objective 1,2,3,4,LDH and early response,(,),For group III and LDH 500 , MTX from 0.5 to 5.0,(,),2 cycles for complete resected disease,(,),systemic chemo plus intravencular therapy for CNS positive patiens,(,),儿童非霍奇金淋巴瘤诊疗建议课件,Improved Cure rate on Children with B-cell ALL and Stage IV B-cell NHL-Result of the UKCCSG 9003 Protocol,British J of cancer 1998,77(12),2281-2285,1990-1996,B-ALL 35, 13 with CNS(+)(L325% blasts),Stage IV B-NHL 28, 22 with CNS(+),9003 based on LMB 86,CNS+, 24Gy in 15 fraction,儿童非霍奇金淋巴瘤诊疗建议课件,9003,Protocol,COP(1)-COPADM1(2)-COPADM2(5)-,CYVE*(8)-CYVE*(11)-COPADM3(14)-,-CYVE#(17)- COPAD(20)-CYVE#(23),COP:,CTX 300mg/m d1,VCR 1mg/m d1,Pred 60mg/m d1-7,IT d1,3,5,儿童非霍奇金淋巴瘤诊疗建议课件,COPADM1,VCR 2mg/m d1,Adr 60mg/m/6h d2,CTX 500mg/m d2,3,4,HDMTX 8g/m/3h d1, CF 15mg/m,Pred 60mg/m d1-5,IT d1,3,5,儿童非霍奇金淋巴瘤诊疗建议课件,COPADM2:,Same as COPADM1,but,VCR d1,6,CTX1.0g/m d2,3,4,CYVE*(HDAra-C):,Ara-C 50/m/over 12h d1-5,Ara-C 3.0g/m/over 3h d1-4,VP-16 200mg/m/over 2h d1-4,儿童非霍奇金淋巴瘤诊疗建议课件,COPADM3,Same as COPADM1, but:,CTX 500mg/m/d d2,3,IT d1,CYVE#(low dose),Ara-C 50mg/m/q12h,d1-5,VP-16 150mg/m d2-4,COPAD:,Same as COPADM3, but no HDMTX,儿童非霍奇金淋巴瘤诊疗建议课件,10,relapse(16%),CNS 2, BM 2, CNS+BM 3, Jaw 1, within 11m after Dx.,2 No-CR, all of the 12 died.,7(11%) died of toxicity,(septic 5, septic + renal failure 2).,43(69%) EFS average 3.1y.,HD-Ara-C possibly play key role,儿童非霍奇金淋巴瘤诊疗建议课件,CD 30 + Anaplastic large cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the french society of pediatric Oncology,Blood 1998;92(10):3591,ALCL- Malignant histocytosis,80-90% T-cell, a few as B-cell,t(2;5), NPM/ALK(nucleophosmine gene/tyrosine kinase gene),10-15% of all NHL,St.Jude stage I/II 28%, III/IV 72%,82 cases , total therapy 7m, no I/T,B-Cell like protocol,儿童非霍奇金淋巴瘤诊疗建议课件,Protocol:,COP-COPAM x 2-(VEBBP-Sequence 1) x 4,儿童非霍奇金淋巴瘤诊疗建议课件,No CNS relapse first,3y SR83%, EFS 66%,No risk factor: 3y EFS 95%, =1 factor 47%,St.Jude I/II: 3y EFS 94%, III/IV 55%,21 cases relapse within 7-49m(median 10m),Risk factor; mediastinal mass,visceral involvement,LDH800,儿童非霍奇金淋巴瘤诊疗建议课件,儿童非霍奇金淋巴瘤诊疗建议课件,Treatment Strategy (B-NHL, Large Cell),Group A (I, II) A B CR A B M2,Group B (III, IV) P A B CR A B A B M12,PR C CR A B C M,Residual CNS+,SL-OP Tumor negative,Tumor positive ABMT,儿童非霍奇金淋巴瘤诊疗建议课件,A,CTX 800mg/m,2,/d1, 200mg/m,2,/d2,3,4,VcR 2mg/m,2,/d1,8,15,Adr 20mg/m,2,/d1,2,Ara-C 500(1000,1500)mg/m,2,/12h/d1,I/T MTX,Ara-C,Dx d1,8,15,B,Ifos 1200mg/m,2,/d1,2,3,4,5,Vp-16 60mg/m,2,/d1,2,3,MTX 15mg/m,2,/d1,2,3,VcR 2mg/m,2,/d8,I/T d1,8,15,M,C:,CTX 1000mg/m/d1,MTX 300mg/m/d15,VcR 2mg/m/d1,8,15,Pred 60mg/m/d1,2,3,4,5,H:,CTX 750mg/m/d1,Adr 25mg/m/d1,2,VcR 2mg/m/d1,Pred 100mg/m/d1,2,3,4,5,CTX in total: 12.45g/m,Ifos in total : 18g/m,Adr in total : 245mg/m,儿童非霍奇金淋巴瘤诊疗建议课件,1994.6-2000.6明确诊断并决定接受治疗者均列入统计,随访至2000.12.30,中断联系超过6个月列为失访,儿童非霍奇金淋巴瘤诊疗建议课件,Results,4/52,gave up treatment within 30 days,44/48,(91%),CR,5/48,lost following-up at CR,5/48,relapsed and,4,died( 85%。,间变型大细胞性淋巴瘤常用标记：,CD30 +，EMA +/-，ALK +/-,淋巴母细胞型淋巴瘤（,LB）,常用标记,T-LB：,B-LB：,TdT +,TdT +,CD1a +/-,CD10 +/-,CD3 +/-,CD19 +,CD7 +,CD79a +,儿童非霍奇金淋巴瘤诊疗建议课件,分子生物学检查,Burkitts,淋巴瘤常见,t（2；8），t（8；14）,或,t（8；22）。,间变型大细胞性淋巴瘤常见有,t（2；5），ALK/NPM,融合。,儿童非霍奇金淋巴瘤诊疗建议课件,疾病分期检查,（分期标准 建议采用,St.Jude,分期系统）,骨髓涂片,胸腹影像学检查（正侧位胸片、腹部盆腔,B,型超声或,CT、MRI）,脑脊液离心甩片找肿瘤细胞，必要时头颅,MRI,以除外颅内转移。,选择性全身骨扫描,儿童非霍奇金淋巴瘤诊疗建议课件,治疗,治疗手段以化疗为主，手术和放疗为辅,放疗：除中枢浸润、脊髓肿瘤压迫症、化疗后局部残留病灶、姑息性治疗等特殊情况外，不推荐放疗。,手术：手术主要用于下列情况：,儿童非霍奇金淋巴瘤诊疗建议课件,除手术活检外，无其它方法可明确诊断并作免疫分型时积极考虑活检术,估计肿块不能完全切除时应仅做小切口活检术，不推荐肿瘤部分或大部分切除术。,急腹症,二次活检,在落后地区如无条件化疗，对于局限性疾病可采用手术治疗，但复发进展率很高。,儿童非霍奇金淋巴瘤诊疗建议课件,急诊处理：,气道及上腔静脉压迫症状气道及上腔静脉压迫症状,胸膜腔积液或心包积液时可引流改善症状,肿瘤细胞溶解综合症,儿童非霍奇金淋巴瘤诊疗建议课件,B-NHL（,成熟,B-ALL）,适应症:,未治,B,细胞性,NHL（,无条件作免疫分型时病理形态为,Burkitts,型,NHL）、,或病理形态为大细胞型。,未治成熟,B-ALL（,即骨髓中大于30%肿瘤细胞表达,SIgM,或/和,轻链，或肿瘤细胞有,t（8；14）、t（8；22），t（8；2）,各脏器功能基本正常。,无先天性免疫缺陷病，无器官移植史，非第二肿瘤。,儿童非霍奇金淋巴瘤诊疗建议课件,分组及治疗计划,分组,R1,组 化疗前已完全缓解，,LDH,正常。,R2,组,LDH,小于正常2倍的,I, II,期，包括孤立,性骨病灶。,R3,组,III,IV,期，或,LDH,大于正常2倍。,R4,组 2个疗程未获完全缓解者。,儿童非霍奇金淋巴瘤诊疗建议课件,R4,儿童非霍奇金淋巴瘤诊疗建议课件,儿童非霍奇金淋巴瘤诊疗建议课件,T-NHL（,淋巴母细胞型）,适应症:,未治,T-,细胞性,NHL（,或病理形态为淋巴母细胞型,NHL）.,各脏器功能基本正常。无先天性免疫缺陷病，无器官移植史，非第二肿瘤.,分组,R1,组 完全缓解（即手术已完全切除肿块）、,I,期，,LDH,小于正常值2倍。,R2,组,I,期，,LDH,大于正常值2倍。,II,期及孤立性骨病灶。,R3,组,III, IV,期。,儿童非霍奇金淋巴瘤诊疗建议课件,图2-,T-NHL,治疗计划,儿童非霍奇金淋巴瘤诊疗建议课件,T-NHL,化疗方案及剂量表,R1,R2,R3,日期,Drug,Dose,Day,NO,NO,NO,NO,Yes,Yes,Course I,PVA+L,CAT,Pred,VcR,Dox,L-Asp,（,美国）,CTX,6-TG,Ara-C,45,mg/m,2,/d,1.5mg/m,2,/iv,30mg/m,2,/2h,10000u/m,2,（,日本,X 0.7）,750mg/m,2,/2h,75mg/m,2,2000mg/m,2,/2h/q12h,1-28,taper 3+3,1,8,15,22,5,12,19,26,5,7,9,11,13,15,17,19,29,43,57,29-35,43-49,57-63,29-30,43-44,57-58,Yes,Yes,Yes,Yes,NO,NO,Course II,PVA+L,CAT,Pred,VcR,Dox,L-Asp,（,美国）,CTX,6-TG,Ara-C,45,mg/m,2,/d,1.5mg/m,2,/iv,30mg/m,2,/2h,10000u/m,2,（,日本,X 0.7）,1000mg/m,2,/2h,75mg/m,2,75mg/m,2,/sc/q12h,1-28,taper 3+3,1,8,15,1,8,15,1,3,5,7,9,11,29,29-35,29-35,Yes,Yes,Yes,Course M,MTX*,CF,MTX/IT,Ara-C/IT,DX/IT,6-TG,3000,mg/m,2,/12h,12mg/m/36h, q6hx4 iv,12.5mg/m,2,(Max 12,5mg),30mg/m,2,(Max 50mg),2.5mg, 5mg(3y),75mg/m,2,1,15,1,15,1,15,1,15,1-7,15-21,儿童非霍奇金淋巴瘤诊疗建议课件,NO,NO,Yes,Yes,Yes,Yes,Course II*,PVA+L,CAT,DX,VcR,Dox,L-Asp,（,美国）,CTX,6-TG,Ara-C,10,mg/m,2,/d,1.5mg/m,2,/iv,30mg/m,2,/2h,10000u/m,2,（,日本,X 0.7）,1000mg/m,2,/2h,75mg/m,2,75mg/m,2,/sc/q12h,1-14,taper 3+3,1,8,15,1,8,15,1,3,5,7,9,11,29,29-35,29-35,NO,Yes,Yes,Course M,MTX*,CF,MTX/IT,Ara-C/IT,DX/IT,6-TG,3000,mg/m,2,/12h,12mg/m/36h, q6hx4 iv,12.5mg/m,2,(Max 12,5mg),30mg/m,2,(Max 50mg),2.5mg, 5mg(3y),75mg/m,2,1,15,1,15,1,15,1,15,1-,7,15-21,2-,NO,NO,Yes,Course C,Ara-C,VP-16,300,mg/m,2,/2h,200mg/m,2,/2h,1,4,7,1,4,7,Yes,104W,Yes,112W,Yes,112W,Maintenance,MTX *,6-TG*,VcR,Pred,20,mg/m,2,/w/po,50mg/m,2,/d,1.5mg/m,2,/q4w,45mg/m,2,/7d/q4w,IT*,MTX,Ara-C,DX,12.5,mg/m,2,(Max 12,5mg),30mg/m,2,(Max 50mg),2.5mg, 5mg(3y),Qwx4(R1),Qwx6(R2),Qwx8(R3),儿童非霍奇金淋巴瘤诊疗建议课件,