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henmotapoietic stem cell transplantation, HSCT k HSCT HSCT HSCT HSCT HSCT HLA graft versus host disease, GVHD 50 HLA GVHD graft verus leukemia, GVL HLA



transplantation,al-lo-BMT allogeneic bone marrow transplantation,al-lo-BMT 1 allo-BMT 1acute myelogenous leukemia, AML50 60 antecedent hematologic disease [ inv16, t(16;16),t(8;21)] [ +8t(9;11)] HSCT3 -7 -55q AML allo-HSCT AML allo-HSCTAML M3 A
1
-

CR2 allo-HSCT PML/RAR HSCT allo-HSCTM3 allo-HSCT 2acute lymphoblastic leukemia-a, ALL t(4;11),t(8;14) t(9;22) ALL first complete remis-sion,CRIallo-BMT allo-HSCT 2chronic myeloid leukemia,CML 50 allo-BMT 1 allo-BMT CP2 allo-BMT CML-CP2 allo-HSCTCML allo-HSCT allo-HSCT 3myelodysplastic syndrome,MDS MDS International Prognostic Scoring System,IPSS MDS -1-2 3-9-1 3-9-2 HSCT -1 -1 55 ECOG0,1,255 -2 55 allo-HSCT 3-9-1 MDS IPSS % Marrow blasts Karyotype cytopenias 0 5 0-1 05 5-10 2-3 10 15 11-20 20 21-30

3-9-2 MDS 1 0

2

-1 -2 1NCCN Practice Guideline in Oncology-v.1.2004

0.5-1.0 1.5-2.0 2.5

4 HSCT HSCT 5 autologous BMT, ABMT ABMT HLA 6 /CLL/SLL

 HSCT HSCT + CD20 CR PR HSCT HSCT B ӂB HSCTBurkitt T allo-HSCT 7BMT 1 BMT severe aplastic anemia, SAA 20 GVHDSAA BMT 2 3 paroxysmal nocturnal hemoglobinuria, PNH m BMT 50 55
3

HSCT HSCT HSCT 65 HSCT 1 BMT 2 3 4 5 HSCT 6EB 7HLA major histocompa-bility complex, MHC human leucocyte antigen, HLA, HLA E 400 200 HLA- HLA-AHLA-BHLA-C HLA- HLA-DRHLA-DQHLA-DP 1 HLA HLA 18 HLA-A35 HLA-B8 HLA-C14 HLA-DR DNA HLA 2 HLA D ˧ D HLA 3 30% HLA PCR-RELP PCR-SSO PCR-SSP PCR-SSCP PCR-DNA 8 1HLA BMT HLA 25% 2HLA ˨ HLA
4

BMT HLA noninherited maternal antigen,NIMA noninherited paternal antigen,NIPA 3 25 -30 HLA HLA 2002 800 HLA 22 ^ 1992 HLA 4 HLA HLA HLA ˦ NIMA 5 55 GVHD 9 ػABO 10 1 1 600-800ml 1

1 2 3 1total body irradiation, TBI 3-9-3 TBI 6-14 Gy1 1 1.8gm d 60mg/(kgd)2 3 4 2 TBI 3-9-4 1.8g(m d) 60mg/(kgd)2 3
5
2 2

4 1mg/kg q6h4-9 9 8 7 6 BMT TBI TBI TBI 3-9-3 TBI Cy /TBI :Cy TBI Cy//TAI :Cy TAI Cy/VP /TBI:Cy VP TBI TBI/TT /Cy /ATG : TBI TT Cy ATG TBI/VP:TBI VP AC /TBI:Ara-C TBI AEL /TBI:MEL TBI
9) 8) 7) 6) 5) 4) 2) 3)

120mg/kg 12-14.40Gy 20 -120mg/kg 4-7.5Gy 120mg/kg 30-60mg/kg 12-13.5cGy
1)

60mg/kg 2-2.4Gy(2/d) 10-60mg/kg 4-7.5Gy 60mg/kg 30-60mg/kg 2-2.25Gy(2/d)

iv(1h)

(d) -6, -5 -3, -2, -1

iv(1h)

-4, -3 -1

iv(1h) iv(2h)

(d) -6, -5 -4 -3, -2, -1

15Gy 10mg/kg 120mg/kg 120mg/kg 12-13-5Gy 60mg/kg 36g/m 12Gy 110-140mg/m 12Gy
2 2

1.25Gy(3/d) 5mg/kg 60mg/kg 30mg/kg 2-2.25Gy(2/d) 60mg/kg 3g/m (2/d) 2Gy(2/d) 110-140mg/m 2Gy(2/d)
2 2

-9, -8, -7, -6 iv(1-2h) iv(1h) iv(5-6h) -5, -4 -3, -2 -6, -5 C4 -3 iv(2h) iv (2h-q12h) -9, -8, -7 -6, -5, -4 -3, -2, -1 Iv(1h) -3 -2, -1, 0

1)2Cy3TBI4TAI 5VP6TTThiotepa 7ATG8AC 9MEL

6

3-9-4 Cy Cy/ATGCy ATG Bu/Cy: Bu Cy Bu/MEI: Bu MEL Bu
1)

200mg/kg 200mg/kg 90mg/kg 16mg/kg 120mg/kg 16mg/kg 140mg/m
2

50mg/kg 50mg/kg 30mg/kg 4mg/kg 60mg/kg 4mg/kg 140mg/m 4mg/kg
2 2

iv(1h) iv(1h) iv (8-10h) 6h 1 iv (1h) 6h 1 iv (1h)
2

(d) -5, -4, -3, -2 -5, -4, -3, -2 -5, -4, -3

-7, -6, -5, -4 -3, -2 -5, -4, -3, -2 -1 -5, -4, -3, -2 -1 -6 -5, -4, -3, -2 -5, -4, -3, -2 -1 -8, -7, -6 -8, -7, -6 -5, -4, -3, -2 -6 -5, -4, -3 -5, -4, -3 -5, -4, -3 -7 -7 -6, -5 -4, -3, -2 -6, -5, -4, -3 -6, -5, -4, -3

160mg/kg 100-200mg/ m 300mg/ m
2

MEL BEAM: BCNU Etposide Ara-C Mel CBV:BCNU Etoposide Cy BAVC: BCNU Amsacrine
3) 2)

100-200mg/ m 300mg/ m
2

iv (1h) iv (2h)

400-800mg/ m

2

100-200mg/ m 200-400mg/ m 140mg/ m
2

2

iv (2h) iv (2h) iv (1h)

800-1600mg/ m 140mg/ m
2

2

2

300-600mg/ m

2

100-200mg/ m 250-800mg/ m 1.2-1.8g/m 800mg/ m 150mg/ m 150mg/ m 300mg/ m 200mg/ m 1g/ m
2 2

2

iv (2h) iv (2h) iv (1h) iv (2h) iv (2h) iv (2h) iv (2h) iv (2h)

750-2400mg/ m 4.8-7.2g/ m 800mg/ m 450mg/ m 450mg/ m 900mg/ m 200mg/ m 1g/ m 4g/ m
2 2 2

2

2

2

2

Etoposide Ara-C LACE: CCNU Etoposide Ara-C Cy CCBCy Cistoplatin
4)

2

2

2

2

2

2

2

2.0g/ m
2

2

iv (2h) iv (1h)
2

5.4g/ m

1.8g/ m
2

2

5625mg/ m 165mg/ m

1406.3mg/ m 41.2mg/ m
2

iv (2h) iv

2

7

BCNU CTCb: thiotepa Cy Carboplatin
6) 5)

600mg/ m 500mg/ m

2

600mg/ m 125mg/ m
2

2

iv (2h) iv
2

-3 -7, -6, -5, -4 -7, -6, -5, -4 -7, -6, -5, -4 -6, -5, -4, -3 -6, -5, -4 -6, -5, -4

2

2

6g/ m

1.5g/ m
2

iv iv iv (2h)

800mg/ m
7)

200mg/ m 4g/ m
2

2

ICE:lfosfanide Carboplatin Etoposide

16g/ m

2

1.8g/ m 1.5g/ m

2

600mg/ m 500mg/ m

2

iv iv 2h(Bid)

2

2

1)Bu2Etoposide3Amsacrine4Cistoplatin 5Thiotepa6Carboplatin7Ifos-famide 3-9-2 3-9-4 Apperley J, Bacigalupo A, Friedrich W, et al. Principles of conditioning Regimens. In:Apperley JF, Gluchman E, Grawohl A, et al. Blood and Marrow Transplanta-tion The EBMT Handbook 2000 Revised Edition. 92-109 2 11640 1000ml 12500U/ 5 20ml 2.5ml 5-10ml 2 Thomas 62 88 16 9 1 3 2-410 /kg 310 /kgK ABO 4 1L+ + A B AB O A B AB 1 6%hy-droxyethyl starch,HES 45 HES 41 2 ABO A B
8
8 8

2L+ A B O AB O 12000 1:2000 3 A B B A L 5 6 100ml GVHD B T NK GVHD T allo-HSCT HLA allo-HSCT GVHD GVHD GVHD T B ŧ 1 10 2 3 1֨ E I
9

2 3¨ B 400mg/d B allo-HSCT 4ߨ cytomegalovirus, CMVganciclovir; DHPG 24 CMV 5-10mg/kg 2 10-21 0.510 /L Foscarnet Sodium injection DNA 60mg/kg q8h 1 2-3 90-120mg/kg 4 37.5 o 1s 3-5 T 3-5 2 45%-90% G 3-5 B
10
9

B B B B o 400-800mg/d 2 200mg/ 2 200mg/d 1 14 voriconazoleEchinocandins B caspofunginû 5

/- rhG/GM-CSF 5-10g/(kgd)+5 0.510 /L. GVHD 1 5000-6000ml 4 6 2 3 pH 7-8 4-Mesna 03 69 1 12%-160% 3 CMV ߧ 1-2mg/(kgd)0-+90 hepatic veno-occlusive diease,HVOD VOD
11
9

VOD VOD 1 VOD E1prostaglandin E1, PCE1 VOD ߧPGE1,0.3g/(kgd) recombinant tissue plasminogen aciva-tor, rh-gPA graft versus host diseaseGVHD GVHD allo-BMT 100 GVHD100 GVHDGVHD GVHD GVHD 1GVHD 1 HLA 2 3 4 5 CM 9-5 3-9-6 3-9-5 GVHD 0 1+ 2+ 3+ 4+ 25% 25%-50% 2mg/d1
1

500ml/d 500ml/d 1000ml/d 1500ml/d

2-3mg/d1 3-6mg/d1 6-15mg/d1 15mg/d1

11ml/d1=17.1mol/L

12

3-9-6 GVHD () () () () 1+2+ 1+3+ 2+3+ 2+4+ 0 1+ 2+3+ 2+4+ 0 1+ 2+3+ 2+4+ 0 1+ 2+ 3+

3 GVHD 1ciclosporin A, CsAmethotrexate, MTX MTX 15mg/m +1 10mg/ m +3 +6 +11 CsA2.5mg/(kg d) GVHD 40 226.4 mol/L2mg% 50 5% 6 CsA CsA 200-400ng/ml 2 MTX MTX15mg/ m +1 10mg/ m +3 +6 +11 10mg/ m 1 100 3FK506Tacrolimus, FK506 CsA CsA CsA 0.03mg/(kgd)24 10-20ng/ml 4Mycophenolate mofetil, MMF, MMF T B MMF CsA GVHD2g/d 5 T HLA kߧ BMT HLA MBT T CD25 GVHD 4 GVHD 1 CsA MTX GVHD GVHD 2-20mg/(kgd) 2mg/(kgd)
2 2 2 2 2

13

ا 3 7 14 2 15-20mg/(kgd). 2anti-ghymocyte globulin, ATG ATG GVHD 10-15mg/kg7-14 ATG 3OKT3 IL-2 CD25 TNF 4MMF FK506 5 GVHD 5 GVHD GVHD GVHD GVHD GVHD 6 GVHD GVHD GVHD CsA 1mg/(kg d) CsA6mg/(kgd),q12h CsA CsA 1 1 2 T 3 2 1 2 T BMT BMT 2-3 BMT T BMT GVHD GVHD GVHD
14

GVHD ٦ʧ AML CRI 20%-25% 1 CR2 40%AMI 60%ALL CRI 25%35% CR2 45% CR2 55% 75%CML 20% 50%80% 1 BMT adoptive immunotherapy IL2 LAK cytokine induce killer,CIK minimal residual dis-ease, MRD donor lympho-cyte infusion, DLI 2 BMT ħ BMT peripheral blood stem cell transplantation,PBSCT.

ABMT autologous bone marrow transplanation, ABMT 1 HLA allo-BMT M3 CR2 PML/RAR 2CML ABML Ph + ABMT 3multiple myeloma, MM MM ABMT allo-BMT ABMT ABMT 4Hodgkin Disease, HD + 40% 5%-10% 1 HD 2 CR 5non-Hodgkin lymphoma,NHL
15

ABMT 1

BCNU 3 1 CR GR 2 CR PR 3 6 w ݧ 2 3

4 Ewing 5

allo-BMT allo-BMT 0.510 /kg
16
8

ABMT 800-1200ml dimthyl sulfoxide, DMSO 1 1 2 2 ABMT ȧ CD34 14C 4C]駵 4C 72 ABMT k 2-196 20%DMSO 10% AB 1-2/min -80 -196 10 3-80 5%DMSO 6%HES -80 1
17
+

40 1-1.5 ABMT allo-BMT 1 ABMT Ara-C MTX VP-6 է CRI ABMT 2 3 MRD 4adoptive immunotherapyIL-2LAK CIK 5 GVHD GVL CsA 2 ABMT PBSCT


transplantation,PBSCT peripheral blood stem cell transplantation,PBSCT

1/10-1/100 PBSCT k PBSCT PBSCT CD34 1 Cy Ara-C
18
+

VP-16 Cy4-7g/m Ara-C2-3g/m VP-16 2.0g/ m
2 2 2

2 G-CEFGM-CSFIL-3 G-CSF GM-CSF PBSC G-CSF GM-CSF G-CSF+GM-CSF G-CSF G-CSF+GM-CSF GM-CSF G-CSF5g/(kg d) 6 3 GM-CSF 0.1 10 /L G/GM-CSFG/GM-CSF mononuclear cella, MNC CD34 1 PBSCT MNCCD34
+ + 9

CFU-GM 1MNC MNC MNC 2CD34 CD34 CD34 3GM-CFU 2
19
+ + +

2 CD34 peripheral blood stem cell,PBSC PBSC 2-3 1-210 /L G-CSF WBC 5-1010 /L 5010 /L CD34 1% 0.2%0.1% 3 PBSC PBSCT ֧ͧ
+ 9 9 + 9

+

PBSC PBSC CFU-GMCD34 MNC Ҧ CUF-GM 210 /kgCD34 210 /kgMNC 710 /kgMNC 710 /kg PBSC 3-4 PBSC ] 4C-80 196C PBSC ԧDMSO
6 8 5 5 +

non-myeloablative allo-geneic hematopoietic stem cell transplantation,NST
20

graft versus leukemia, GVLgraft versus tumor, GVT NST 150-60 70 2 HSCT 3 4 5 DLI GVL NST m SLE 1 28 ^ 2 1fludarabin 30ml/(m d)6 Busulfan 4mg/(kgd)2 ATG5-10mg(kgd)4 2fludarabin 30mg/(m2d)6 TBI200cGy1 3 fludarabin 30mg/(m2 d)4 Melphalan 140-180mg/(m d) 1 4mg/(kgd)2 4fludarabin 30mg/(m d)3 Busulfan Cy350mg(m d)3 NST T
21
2 2 2 2

T GVHDGVL/T NST CsA MTX MMF1.0/ GVHDCsA 3-6 MMF0-30 1 ABO ABO ABO

ABO ABO ^ ABO 2

Ph ] t(8:21) bcr/abl 3 ɧڡ NST DNA ާ ɧۉ ۦ DLI T 1DLI GVHD DLI 30 GVHD 2 DLI bulik dose regimen, BDR

escalating dose regimen, EDR EDR GVL GVHD 3CD3
8 +

110 510 110 DLI 1.210 /kg(0.0510 /kg-2.7
+

7

7

8

8

8

10 /kg) HLA CD3 HLA CD3 104/kg
+

22


+ CD34 +

CD34 CD34 CD34 CD34 1 MRD PBSC CD34 CD34 CD34
+ + + + +

+

+

CD34 CD34 PBSCT 2 CD34 HLA GVHD CD34 CD34 T GVHD ^ 3CD34 CD34 CliniMACS G-CSF Cs3000plus CD34
+ + + + + + + +

CliniMACS ˧ CliniMACS CliniMACS CD34 96% 67%T 95%
+

23



umbilical cord blood, CB1988 Broxmyer Gluckman Fanconi GVHD HLA HLA HLA- ܞQ HLA-ABCDR DNA

1HLA HLA-AB HLA-DR HLA DRBA 2 210 /kgCFU-GM1.510 /kgCD34 1.510 /kg 1 12 2 5 3 5-7cm ާ ACD CPD A cirate/phos-phate/dextrose/adenine/// CPD A
24
5 7 4 +

pH CB 16 CPDA 23ml 170ml 2% 75% 42-240ml 4 6%HES 1:5 HES: CB 10,50g,5

mononuclear callMNC160ml 400g10 MNC 20ml 5 6 HLA HIV-1 HIV-2CMVHTLV-1 ۜZ pMNC HLA -80 1 -196 10

HLA ֧ 1 2 3 4 ¦

25


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