1 ??????????????,????????,????????????,????????????????? 2 ???????(????????)?????,??????????????????? 3 ???????????????????,??IL-1,IL-6,TNF???IL-8????????????? 4 ??T?????B??????? 5 ????????????????CSF? 6 TNF????IFN??????,???CTL??MHC-1????

1
????????????

• ????????????
• ??????????

2
??????

• ?????2000?5?
• ?????????
• ??37?????,???????
• ?6?(?)
• ??2830?
• ??1012
• ??1416
• ?? 3

3
??????

• ?????,???????,??
• ?????,???????,??
• ?????,????
• ????
• ??? ?????
• ??? ????
• ? ? ????
• ? ? ????
• ? ? ?????

4
??????

• ??????????????????
• ????????????
• ?????????????????

5
?????????

• CML???????????
• ? ??????? (CP?BMT?5?LFS 80)
• ? ??????(????)??/???
• ? ????? (???????????,3?PFS 70)
• ? RT-PCR????MRD (bcr-abl)????
• ??ALL?????????????
• ? ??????(182?)??????
• ??????????ABMT? 5?LFS 60.5
• ??????????BMT? 5?LFS 52.5
• ???????????????? 5?LFS 25.3
• Ph ALL?????????????????????
• RT-PCR????MRD(IgH??)????

6
?????????

• ?????????????????
• ? ??????(432?)????????,?????
• MM???????????(04??????????)
• ? ??????/??ABMT????3?PFS 70
• ? ?????3?OS????
• 80S 90S
  00-05
• ????(?) 21.0 28.0
  36.0
• 3?OS() 14.5 32.8
  52.5
• ? ?????
• ??????????
• ABSCTNST
• ??????THAL??, VELCADE??

7
?????????

• ??????????????????
• ? ???????????IV?????
• ? ??ALL????????????????
• CD20 B??NHL?????ABMT/BMT
• ???T-NHL ??BMT/ABMT
• ??NHL?Flu??????
• ? RT-PCR????MRD(IgH??)????
• ??????????????
• ? ?????????????
• ? ?3?????82??,TRM 7?(8.53),
• ??ABMT?0,BMT?12.5
• ? ???????,????20?,???8???(10)

8
?????????

• ???????????????
• 2000-2002, ???????????
• ????????????????
• 2001-2004, CMB(?????????)?? ?????
  ???1-748
• ????????????????????
• 2001-2003,????(???) ???95-?-10
• ?????????????????????
• 200O-2003,??????????? ???003119811
• DC???????????????
• 2001-2003, ???????, ???wkz-2001-34
• ??????????????
• 2002-2004,????????, ????? ???013111111
• ???????????????
• 2002-2004,??????? ???013609411
• ????????????????????????
• 2004-2006,???????????????,??0438031111
• ?????????
• 2005-2007,???????????????,??05YFSZF02400

9
???????????????

• IFN-a HHT??CML (????)
• ???????APL II?????(????)
• ???????APL II?????(????)
• R-CHOP??CD20B-NHL
• ???????ASCT??CD20B-NHL
• FC/FND??????NHL
• ??????CML(GIPAP??????)
• ?????BMT????CML
• ???EPO(???)????????
• ?3???????MM????III????
• ????????????MM
• DVD??????MM

10
????????

• 2003?????2002?????????(?4)
• ??????????????????
• 2003?????2002????????? (?3)
• ???????????????
• 2004?????2003????????? (?2))
• ????????????????????
• 2005?????2004????????? (?7)
• ???????????????????????

11
?????

• ????52?,??SCI??4?
• ????????40?
• ??????50??,??SCI??14?
• ????????????????20?(?)
• ??????(???,?????,04?5?)
• ????6?

12
????

• ?????
• ??12?(??????6?)
• ??4?,??8?
• ?????
• ????28?,??9?
• ??23?,????10?
• ??14?(????7?)

13
??????

• ???????
• ?? ?? ?? ???
• ??????
• ???????????
• ?????
• ????????97???

14
???? ???????? ????
Thanks!
15
??ALL???ASCT?????

• ???????? ???????
• ????? ?????????

16
?????

• ?? ????????????ALL???
• ??
• 1??????????????,??CR??
• 2?????????4??,???????
• ASCT,??ASCT????,??ASCT??
• 3?ASCT????????,?????MRD,
• ?????,??????
• 4????ASCT?,???????2-3?????

17
????

• ??????
• ??????
• ????
• (??/????4-6?)
• ASCT ??????
• ??CNSL??/??

18
????

• ???? VD(M)C/(L)P
• ????
• HD-MTX(3.0g/?) L-asp 10000IU/d
  7-10d
• HD-Ara-C(1g/?,q12,6-8? MTZ
  (10-12mg/?/d 3)
• HD-CTX(50-60mg/?/d2)
• ????
• VD(M,A)C(L)P, E(T)A, EOAP,VACEP
• CNSL??/??
• ITDXM 10mgMTX 10mgAra-C 50mg,
• ?CNSL 2?/??,
• ?CNSL 2-3?/?, CSF??? 2?/??
• ???? 18-24Gy(?TBI?)

19
???ASCT????LFS??
?????????()
20
???ASCT????OS??
? ? ? ?()
21
ASCT??????????????LFS??
???????()
22
??hyper-CVAD????????Ph ALL
23
??hyper-CVAD ????

• ?????????VD(M)CLP??
• CVAD Dexm ??30mg, ??M.D. Anderson
• HD MTX-Ara-C
• MTX ??,
• Ara-C ??1.0g/m2, 4-6h, q12h, d2-4(6?)
• ?????
• ???? 400mg/?,???14??

24

• ??????
• ??? 8
• ?? ??
  6?,?? 2?
• ???? 24(16-42)?
• ??
• Pre-B/c ALL 5
• Pro-B ALL
  1
• Pre-B-LBL /ALL 1
• CML-ALL (?) 1
• ???????? 16

25

• ????
• HCR 8/8
• CyCR 7/8 (CML-ALL NR)
  
• mMCR 7/8 (FISH -)
• MCR 4/8 (RT-PCR-, Q-PCRlt10-5,)
• 
  1?ASCT?mMCR,ASCT??MCR)

26
???hyper-CVAD
WBC???(109/L) ANClt0.5109/L(?) BPClt20109/L(?)
0.47(0.13-2.81) 3.5(0-9) 0 ?10??,2?????8?14?(???????4?)

• ?????????(2/12,16.7),????(1/12,8.3)
• ??3/12(25)?-????,????????????

27
???HD-MTX Ara-C
WBC???(109/L) ANClt0.5109/L(?) BPClt20109/L(?)
0.10(0.04-0.28) 10(4-15) 9(1-14)

• ???????????(9/12,75),
• ?????WHO
  1-2?(6/12,50)
• ??(4/12,33),???????(1
  /12,8.3)
• ?-????(5/12,42)
• ??4???-????,????????,??,??,??
• 2??????,??G-???/???

28
????
?????,?,16?,?????????1?,????2? ??????????WBC
17.5109/L,RBC 3.161012/L,HGB 93g/L,PLT 51
109/L,????????95.5,POX(-),??ALL,?2004?7?1??????
???? ??????????,?????,??????????,??????,?????
,??(-),??,?????,???????,??????,???????
?????????Ph-BCR/ABL- P190 ALL,????VMCLP,HD-MTX
Ara-c?3??Hyper-CVAD????????,??13???,??????CR,?2??H
yperCVADMA???BCR/ABL P190??(RT-PCR).
29
2004.7.1 ??Ph/BCR-ABL P190()Pro-B-ALLTCR?(
),IgH()
2004.7.6-8.2 VMCLP
2004.8.10 ??CR46,XY13FISH/RT-PCR ()
2004.8.24-8.27 HD-MTXAra-c
2004.9.16 ??CRFISH (-), RT-PCR()
2004.9.30-10.18 HyperCVAD
2004.11.8 ??CR FISH (-), RT-PCR()
,TCR?(),IgH(-)
2004.11.22-12.11 HyperCVAD
2005.1.10 ??CR46,XY15 FISH (-), RT-PCR(-)
2005.1.25-2.19 HD-CTXG-CSF
2005.3.15 ??CRBM?PBSC FISH (-),
RT-PCR(-)
(????? 400mg/?, d1-14,??????)
30
??ALL????
????ALL
31
??MM??????????

• --???25??????

32
Purpose of the study

• Based on the retrospective study of large series
  in a representative centre, conclude clinical
  features, response to current treatment and
  prognosis of multiple myeloma in China
• To make new strategy of diagnosis and treatment
  of multiple myelom according to the advance of
  basic and clinical research on multiple myeloma,

33
Patients

• 606 MM patients were recorded in BHD, CAMS
• from 1980 to 2002.
• These patients came from 26 provinces.
• 432 were evaluated for clinical features.
• 257 were evaluated for survival analysis with
  enough follow up data.
• 195 were treated with conventional therapy over
  6 months and evaluated for Tx results.

34
Treatment for MM in BDH

• 1980s-1996 conventional CT with MP, M2,
• COP, VECP.
• 1997 VAD, HDTASCT, Allo-BMT
• 2000s Thalidomide MP, VAD/HD-Dexm
• Thalidomide
• 2005 Bortezomib HD-Dexm

35
Epidemiology

• Annual incidence
• USA White 4/100,000 Black
  gt10/100,000
• Europe 2.5-3.5/100,000
• Asia 1.0/100,000
• China no definitive data, probably
  1.0/100,000
• Age at diagnosis
• Western peak age 65-70 y, median age
  68y
• China peak age 55-65 y, median age
  55y
• Male to female ratio 2.51

36
Age and gender distribution of 432 patients with
MM at diagnosis
peak5565y,median57y
Male female2.351
Statistics data of Blood Disease Hospital, CAMS
2004, n432
37
Comparison of age at diagnosis

• BDH ( ) Mayo
  Clin()
• n432
  n1027
• lt40 10.2
  2.0
• 40-49 18.8
  8.0
• 50-59 32.9
  20.0
• 60-69 26.8
  32.0
• gt 70 11.3
  38.0

38
monoclonal-protein type in 312 patients
A retrospective study of 23 years in
BDH,CAMS,2004
39
The stage of 260 patients at diagnosis
A retrospective study of 23 years in BDH,
CAMS, 2004
40
Major complication

BDH Mayo Clin hyperviscosity
60.0 76.0 uricacidmia
39.4 27.0 hypercalcemia
9.1 13.0 renal failure
21.1 19.0 amyloidosis
1.1 6.0
41
Comparison of major hemetological and biochemical
values
BDH
Mayo Clin HB ( g/dL) 7.3
(255) 10.9 (1025) BMPC
38.3 (255) 50.0(1027) CRP
(mg/dl) 5.53 (121) 0.4
(285) LDH 76 mol/L (
181) not given ß2-MG( mg/L)
4.5 (43) 3.9 (735)
42
Plain radiograph

• of 281 patients with entire radiographic data ,
  54 (19.2) have normal findings, 227 (80.8)
  have bone lesions.
• Lytic bone lesions 61.1(180), esp.
• skull(87.2),rib(69.2), pelvis(54.1)
• Osteoporosis38.3(108)
• Pathologic fractures or compression
• fracture22.8(64)
• Osteosclerosis2.1(6)

43
Cytogenetics

• Normal karytype39/70 patients(55.7)
• Chromosome 13 deletion/hypodiploidy(-13 or 13q-)
  4 cases, female, with a median survival of
  15.7m(range,13-19)
• Chromosome 14 deletion/translocation 5 cases
• Chromosomal aberration-16 in 3 cases,-8 in 3
  cases ,10 in 2 cases ,ctb(4) in 2 cases, others
  were not accounted because of limited number.

44
257?MM???????
??????????????(2004?) (n257,
??????2004??4?)
45
????MM?????

• TIME PERIOD N MEDIAN SUVIVAL 3
  YRS OS 5YRS OS
• 1980-1989 58 21.0 m
  14.5 8.6
• 1990-1994 68 25.5 m
  28.6 18.5
• 1995-1999 72 29.0 m
  35.8 28.6
• 2000-2005 126 36.0 m
  51.2
• Total 257
  28.0 m 38.8 23.2
  

46
MP versus combination

• items MP combination
  P?
• (n49)
  (n146)
• response rate 30.4
  50.3 0.02
• rate of CR 4.8
  18.1 lt0.01
• Failure 36.9
  21.5 lt0.05
• survival duration 30m
  30.5m gt0.05
• 3y OS 26.0
  36.9 gt0.05
• 5y OS 17.2
  23.7 gt0.05

Data of blood disease hospital, n195, 2004
47
MP versus combination
Data of blood disease hospital,n257,2004
48
Effect of IFN as maintenance therpy
Median survival IFN 46 m (n38)
non-IFN 30.5 m (n108)
Data of blood disease hospital ,2004
49
?????????MM

• ???????ASCT??????MM?CR??????OS,ASCT???6065?????MM
  ???????
• Allo-SCT????MM????,??TRM?
• ????????,????MM?HE??
• HLA???????
• ASCTNSCT????????,???????????

50
???????????MM

• Cases
• 13 patients, median age 42(range,32-58)
• IIIA 10 ,IIIB 3
• all with more than one poor factors
• Treatment prior to transplant
• median time 8m (range, 4-15)
• median treatment 5(range,4-9),including
  VAD, MP, M2,
• HD-CTX.
• Disease status at transplant
• CR 4 , PR 6 , stable 2 , progression 1

51
???????????MM

• Transplant
• Double PBSCBM 7 cases
• Single BM/PBSC 6 cases
• conditioning regimen
• Double transplant
• first Mel 160-180mg/m2 (110-140mg/m2 iv )
• Caely 40 mg/m2)
• second sTBI 8GyMel160mg/m2 (140mg/m2 iv)
• Single transplant
• sTBI 8Gy Mel 160-180mg/m2 VP-16 1000
  mg/m2

52
???????????MM

• Diseases status after Transplant
• CR 7/13
• nCR 3/13
• PR 3/13
• Follow up
• Median 24 m (487)
• PFS 9 pts for 32m (1466m)
• Relapsed 4 pts at 13m (4-87),
• DT 1/7 (87m), ST 3/6 (
  4,5,13m)
• 2 pts reached CR after
  Allo-BMT for 13, 6m
• Died 2, DT 1 90m, ST 1 14m

53
Allo-SCT??MM

• ??????MM
• ???????
• ??GVM??,??MRD
• ???????
• ?TRM ????????????TRM 3050?
• ???? Allo-SCT??????????,???
• ??????????
• ??????ASCT, PBSCT?????
• EBMT 1994?334? TRM 43,3?OS 35
• 94-98356? TRM 30,3?OS 56?

54
????????????MM(????????????)

• ??
• 4?,? 2, ? 2,????? 39?45?53?46??
• IgA ? 1?,IgD?1?,????1?, IgG???????
• ???1?
• ?????
• 2?????????,1??ASCT PR 5?????
• ?,1??ASCT?CR 68??????
• ?????
• sTBI 8Gy Mel 160mg/m2 Ara-C 1g/m2
  q12h2d
• VP-16 1000mg/m2

55

• ??
• 1?????58??????????(53?)
• 1????????????CR,???16?
• 1?IgG???????????, ???3??
• PR, ?CSA,???DLI???aGVHD,?6?
• ???cGVHD?????6?,??VG PR?
• ?, ????15?,CR??
• 1?IgA ASCT?CR 68?????,???2
• ?,VGPR?

56
HD-MEL???????MM

• ??
• ?7?,???6?,?1?,????51(31-60)?
• ????????,???VAD?????????
• ?? ????4?(??????? 1?)
• ????5?,????4??(??2??VAD)
  
• ?????3?(??????1?)
• ??2442???
• ??
• ??HD-MEL?? 90-110mg/m2 6?
• ?? 70 mg/m2
  1?

57
HD-MEL???????MM

• ??
• ??? ??,?????????TRM
• ??
• ??? 4/7,??CR 1, PR 2, ?? 1?
• ???? 4?
• ??2?(1?CR,1?PR),??2??
• ????3?
• ??2? (1?????PR,1???)
  
• ??1? (?ASCT CR?13????)

58
IHMM2003 (2)

• ??lt 60?,?SCT??
• ??VAD / Velcade HD-Dexm ?
  23??
• NR
  PR?CR
• Velcade/ HD-MEL ?? HD-CTX
  G-CSF
• (90-110mg/m2 P.O. 70-90mg/m2 iv)
  ????PBSC
• 
  
• NR
  ??ABSCT ??SCT
• 
  (TBIMEL) ABSCT (HD-MEL)
• ????? ALLO-SCT
  3-6m lt50, ???
• (TBIMEL)
  ABMT NSCT
  

59
IHMM2003 (3)

• II?III?,??gt 60?,?lt60??SCT??
• ??M2???
• NR
  PR?CR
• VAD
  ??? IFN-a?????
• 
  (???????PBSC)
• 
  
• NR
  ?????
• 
  (?????SCT)
• HD-MEL?? ALLO-SCT
  
  (TBIMEL)
• ???????
  ASCT ALLO-SCT
  

60
Allo-SCT????NHL

• ??5?
• LBL 3,??T 1,DLCL(????)1,??IVB
• ?????
• LBL VDC(L)P HAM
• ??T Pro-MACE/Cyto-Bom 3??
• DLCL m-BACOD 3?? ????
• CNSL???ALL
• ?????
• CR,CRu(DLCL)

61
Allo-SCT????NHL

• ????
• HLA??????
• ???STBI 9.0-10.0Gy Mel 180mg/m2
• /- VP-16 1000mg/m2
• ??
• TRM 1? (DLCL,6????IP)
• ?? 1? (LBL,9?)
• CCR??3? (8?20?32?)

62
ASCT???????NHL

• ??15
• CR1 5?(LBL III/IV 2,DLCL III/IV 3)
• CR2 6?(DLCL 4,MCL 1,FCL 1)
• PR??? 4?(DLCL 2,LBL 1,???? 1)
• ???
• STBI 9.0-10.0Gy Mel 180mg/m2
• /- VP-16 1000mg/m2
• CD20?????? 2?(DLCL)

63
ASCT???????NHL

• ??
• 1)PR??? 5????CR
• 2)????2?
• TRM 1?
• ?? 5? CR1 1, CR2 2,PR/?? 2)
• ????3?lt1?,1?16?,1?22?
• CCR?? 9? (6?-72?)

64
???? ???????? ????
Thanks!