儿童非霍奇金淋巴瘤诊疗建议.ppt

1、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,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。,NHL Protocol Review,NHL-BFM90 Report (T-LBL)Blood ,2000,95(2):416,0-18y, T-cell, F:M 24:81.106 patients, I:2, II:2, III:82, IV:19. BM(+) 15, CNS(+) 3.Protocol:AL

2、L-like protocol.Induction: CTX 1g/m, d36,64.Re-in d36HDMTX 5.0g/m/24h X 4.Asp X 2（10000/M x 8，x4）CRT：1200 cGy for III/IVTotal CTX 3g, Adr 240mg/m.Total therapy 2 y.,Result5y EFS 90%No different atSex, age,LDH(500), III or IV,immunotyping, d33 CR or not,POG 8704 Report-T-ALLand T-NHLLeukemia 1999;13:

3、335,T-ALL 357caes, T-NHL(lymphoblastic) 195whole protocol basicly like ALLAfter CR:High dose Asp 25000/m/w x 20W from d 99 as consolidationNo high dose Asp consolidation,4y EFS ALL: 68% vs 55% NHL: 78% vs 64%,BFM 90 B-cell ReportBlood 1999;94:3294,Object:LDH and early response For group III and LDH

4、500 , MTX from 0.5 to 5.02 cycles for complete resected diseasesystemic chemo plus intravencular therapy for CNS positive patiens,Grouping,R1: CR, R2: no-abdomen primary or incompletely resect, LDH 500 or multiple bone,BM,CNS involvement,6 cyclesNo-CR after 2 cycles: HDAra-c+Vp-16 for 2 cycles If CR

5、, plus another 3 cycles,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,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,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

6、 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,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,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

7、 xx xx Vp-16 100mg/m/d/1h x x,* 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,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,CC 1 2 3 4 5 Dx 20m

8、g/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,CNS(+) Intraventricularly Chemo, AA and BB MTX 3mg, Pred 2.5mg d1,2,3,4 Ara-C 30mg d5CC MTX 3mg, Pred 2.5mg d3,4,5,6 Ara-C 30mg d7,ABMT Pre-conditioning,-8 -7 -6 -5 -4 -3 -2 -1 0Busulfan 120mg/m* ! ! ! !VP-16 300mg/

9、m/4h ! ! !CTX 1.5g/m/1h# ! ! ! Stem cell transfusion !* Divided p.o# If CNS(+) thiotepa 300mg/m/d x 3 replace of CTX,Result and Conclusion,R1:100%, R2: 96%, R3 78%.HDMTX effective in R2 and R3Stage III, LDH500u/L, PEFS 81%, control 43%. 6y EFS ABMT(residual after 3 cycles) effective, 5/6 survived, c

10、ontrol: 4/5 progress.,Confirmed the objective 1,2,3,4LDH 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 (),Improved Cure rate on Children with B-cell ALL and Stage IV B

11、-cell NHL-Result of the UKCCSG 9003 Protocol British J of cancer 1998,77(12),2281-2285,1990-1996B-ALL 35, 13 with CNS(+)(L325% blasts)Stage IV B-NHL 28, 22 with CNS(+)9003 based on LMB 86CNS+, 24Gy in 15 fraction,9003 Protocol,COP(1)-COPADM1(2)-COPADM2(5)- CYVE*(8)-CYVE*(11)-COPADM3(14)- -CYVE#(17)-

12、 COPAD(20)-CYVE#(23)COP: CTX 300mg/m d1 VCR 1mg/m d1 Pred 60mg/m d1-7 IT d1,3,5,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,COPADM2: Same as COPADM1,but VCR d1,6 CTX1.0g/m d2,3,4CYVE*(HDAra-C): Ara-C 50/m/over 12h d1-5 Ara-C 3.0g/m/

13、over 3h d1-4 VP-16 200mg/m/over 2h d1-4,COPADM3 Same as COPADM1, but: CTX 500mg/m/d d2,3 IT d1CYVE#(low dose) Ara-C 50mg/m/q12h,d1-5 VP-16 150mg/m d2-4COPAD: Same as COPADM3, but no HDMTX,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 tox

14、icity (septic 5, septic + renal failure 2).43(69%) EFS average 3.1y.HD-Ara-C possibly play key role,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 histo

15、cytosis80-90% T-cell, a few as B-cellt(2;5), NPM/ALK(nucleophosmine gene/tyrosine kinase gene)10-15% of all NHLSt.Jude stage I/II 28%, III/IV 72%82 cases , total therapy 7m, no I/TB-Cell like protocol,Protocol: COP-COPAM x 2-(VEBBP-Sequence 1) x 4,No CNS relapse first3y SR83%, EFS 66%No risk factor:

16、 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,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+ S

17、L-OP Tumor negative Tumor positive ABMT,A CTX 800mg/m2/d1, 200mg/m2/d2,3,4 VcR 2mg/m2/d1,8,15 Adr 20mg/m2/d1,2 Ara-C 500(1000,1500)mg/m2/12h/d1 I/T MTX,Ara-C,Dx d1,8,15B Ifos 1200mg/m2/d1,2,3,4,5 Vp-16 60mg/m2/d1,2,3 MTX 15mg/m2/d1,2,3 VcR 2mg/m2/d8 I/T d1,8,15,MC: CTX 1000mg/m/d1 MTX 300mg/m/d15 Vc

18、R 2mg/m/d1,8,15 Pred 60mg/m/d1,2,3,4,5H: CTX 750mg/m/d1 Adr 25mg/m/d1,2 VcR 2mg/m/d1 Pred 100mg/m/d1,2,3,4,5CTX in total: 12.45g/mIfos in total : 18g/mAdr in total : 245mg/m,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,Results,4/52 gave up treatment within 30 days44/48 (91%) CR5/48 lost

19、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,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。,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,治疗,治疗手段以化疗为主，手术和放疗为

20、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：,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。,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,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

21、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。,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。,R4,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。,图2-T-NHL治疗计划,T-NHL化疗方案及剂量表,