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1、儿童非霍奇金淋巴瘤诊疗建议（2004讨论稿）,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 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.,Result 5y EFS 90% No different at Sex, age, LDH(500), III or IV, immunotyping, d33 CR or not,POG 8704 Report-T-ALLand T-NHL Leuke
3、mia 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,4y EFS ALL: 68% vs 55%NHL: 78% vs 64% ,BFM 90 B-cell Report Blood 1999;94:3294,Object: LDH and early response For
4、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,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-
5、16 for 2 cycles If CR, plus another 3 cycles,Protocol B-Cell-BFM-90,R1 V-A - BR2 V-AA-BB-CR-AA-BBR3 V-AA-BB-CR-AA-BB-AA-BBPR-CC-CR-AA-BB-CCPROP-NegtivePositive-ABMT,V1 2 3 4 5Pred 30mg/m/d x x x x xCTX 200mg/m/1h x x x x xI/T x,A 1 2 3 4 5DX 10mg/m/d x x x x xIfos 800mg/m/d/1h x x x x xMTX 500mg/m/2
6、4h* x IT xAra-c 150mg/m/q12h/1h xx xxVp-16 100mg/m/1h x x*CF 12mg/m 48,54h,10%MTX/30,90%23.5h,B 1 2 3 4 5Dx 10mg/m x x x x xCTX 200mg/m/1h x x x x xMTX 500mg/m/24h xIT xAdr 25mg/m/1h x,AA 1 2 3 4 5Dx 10mg/m x x x x xIfos 800mg/m/1h x x x x xMTX 5g/m/24h* xIT xVcR 1.5mg/m xAra-C 150mg/m/1h/q12h xx xx
7、Vp-16 100mg/m/d/1h x x,* CF 30mg 42,48h, q6h ajusted as follows:1-2umol/L 30mg/m2-3umol/L 45mg/m3-4umol/L 60mg/m4-5umol/l 75mg/m5umol/L: CFmg=MTXumol/L/kgMTX 10%30, 90%23.5h,BB1 2 3 4 5Dx 10mg/m x x x x xCTX 200mg/m/1h x x x x xMTX 5.0g/24h xIT xAdr 25mg/m/1h x,CC1 2 3 4 5Dx 20mg/m x x x x xVDS 3mg/
8、m(max 5mg) xAra-C 2.0g/m/3h xx xxVp-16 150mg/m/1h x x xIT x,CNS(+) Intraventricularly Chemo, AA and BBMTX 3mg, Pred 2.5mg d1,2,3,4Ara-C 30mg d5 CCMTX 3mg, Pred 2.5mg d3,4,5,6Ara-C 30mg d7,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#
9、! ! ! 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 R3 Stage III, LDH500u/L, PEFS 81%, control 43%. 6y EFS ABMT(residual after 3 cycles) effective, 5/6 survived, control: 4/5 progress.
10、,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-cell NHL-Result o
11、f 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,9003 Protocol,COP(1)-COPADM1(2)-COPADM2(5)-CYVE*(8)-CYVE*(11)-COPADM3(14)-CYVE#(17)- COPAD(20)-CYVE#(
12、23) COP:CTX 300mg/m d1VCR 1mg/m d1Pred 60mg/m d1-7IT d1,3,5,COPADM1VCR 2mg/m d1Adr 60mg/m/6h d2CTX 500mg/m d2,3,4HDMTX 8g/m/3h d1, CF 15mg/mPred 60mg/m d1-5IT d1,3,5,COPADM2:Same as COPADM1,butVCR d1,6CTX1.0g/m d2,3,4 CYVE*(HDAra-C):Ara-C 50/m/over 12h d1-5Ara-C 3.0g/m/over 3h d1-4VP-16 200mg/m/over
13、 2h d1-4,COPADM3Same as COPADM1, but:CTX 500mg/m/d d2,3IT d1 CYVE#(low dose)Ara-C 50mg/m/q12h,d1-5VP-16 150mg/m d2-4 COPAD: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 toxicity (septic 5, septic + renal failure 2). 43(69%) EFS average 3.1y. HD-Ara-C possibly play key role,
