Leukemia

1
??? Leukemia
2
??? ??
??????????????????,?????????????????????
??????????????,??????????????????????,??????????,?
????????
3

?? ???????????????? ????? acute
leukemia
????? chronic
leukemia ?????????? ?????????(acute
lymphocytic



leukemia, ALL)
?????????? (acute non-lymphocytic



leukemia, ANLL)

?????????(chronic lymphocytic



leukemia, CLL)
???????? (chronic
myelocytic



leukemia, CML)

4

• ????
• ?????????2.76/10??
• ????35????????1??
• ???????? 6?(??) 8?(??)?
• ???2.76/10?,?????ANLL 1.62/10?,ALL 0.69/10?,CML
  0.36/10?,CLL 0.05/10?,??????,???????,??????,??????
  ?

5
??????? ?????????????? ?????? ATL
(adult T leukemia)??HTLV-I (human T lymphocy-
trophic virus-I, HTLV-I)??
?????ATL???T???????HTLV-I(1?C
????RNA??)
???????????DNA???HTLV-I???
???????????HTLV-I????????
? ????,??????????ATL???
???? ? ATL?????????HTLV-I??
6
?????? ????????,???????? ???
????????30??17? ??????
????????????????, ???
32P??,??????gt?? ???????????????????,?
?????????
7
?????? ?????(?????gt??3-20?) ???
????????? ???? ?chromosome??
???,??? ??????????
8
???????7 ??????????AL,????????1/
5?? ???? ?Down
Syndrome21,??????50/10?gt???20?
???????????? ???????????(Fanconi)??
? Bloom??? ??????????
??????????????(???????????
??????)
????????,????????????? ??????
CML?????????????,?????
MDS?PNH?lymphoma?MM

9
??? ????? (acute leukemia AL)
10
?? ??????????????,??????????(?????)?????
????????,??????,?????????????,????????? ?
11
?? ? 70??(1976. Benne?)?????7???
??FAB??,?????????? ? 70???????????????????,?A
L?? ??????? ? C hromosome??90AL?????
? ? 80????MIC??(Mmorphology, I immunology,
C

Cytogenetics) ??? MICM(MIC??????)??
12
?? ?? L1
L2 L3
??? M0
M1
M2 M3
M4
M5
M6
M7
13
????????????
M0 (????????????)
???????????????????????,?
?????????L2??,????,????
???,???????Auer ??,
??????????(MPO)????lt3
???????lt3 ???MPO()
????CD33?CD13
?????(-),???CD7 ?TdT M1(????????????)
??????? ????????
? ???????? MPO()gt3




gt90(????? ???)

14
M2(?????????????) ???? 30
89 ????lt 20
?????gt10 ??? M2a?M2?
M2b??????????gt30 M3(??????????)
?????30(?????) M4(??????????)
??????????30 ??????30lt80
???????gt20 M4E0 ??M4????,??????5,(?????)

(????????)






15
M5(?????????) ??????80 M5a??80

M5b??lt 80 M6 (??????) ???? 50
????(?? ?? ) (???) 30 M7 (?????????)
?????? 30 ?????????
L1??????????????(?? 12µm)
L2??????????????(??gt12µm )
L3??????????????,?????
????????,????,???
16

• MICM??
• ??? ( morphology)
• ??? (immunology)
• ????? (cytogenetics)
• ????? (molecular genetics)
• ???????(AML)?WHO??
• ??????????AML
• (1)AML?t(821)(q22q22), AML1(CBF-a)/ETO
• (2)APL t(1517)(q22q11-12), PML/RARa
• (3) M4EO inv(16)(p13q22)
• (4) AML ?11q23(MLL)??

17

• ?????????(ALL)?WHO??
• ?B???????????
• (1)t(922)(q34q11), BCR/ABL
• (2)11q23MLL??
• (3) t(119)(q23q22), E2A/PBX1
• (4) t(1221)(p12q22), ETV/CBFa
• ?T???????????
• 3. Burkitts ?????

18
???? ???? ?????,????
?????,????,???????????? ??????????,?????? ????1
/2?????, ????????? ????????
???????????????
?????
???,???? ???????????
19
???? 40?????,????? M3???DIC
?????62.24,??87????? ????????????
(?)??????? ?????????
???????T???????
???????? ??????
(?)????? ??????
??????????? ????????







20
(?)???(??????????????, granulocytic
sarcoma)

?????,????????,???????,?
???? (?)????? ??????M4?M5
??????????????(?????????
????) (?)?????????(CNS-L)
??????????????CNS-L,??????
?,??????????????? ????(????)
CNS-L?????????????????,?? ?????



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(?)??(??) ?????,?????
?????????????????,??????? (?)??????
???????????? ????? ????1.WBC?
(??),???????30-90,?
?gt95 ???????WBCgt100109/L
??????????WBC?????(??

lt10109/L )
?????????
2.HGB? (?????)???? 3.PLT?
50lt 60109/L ,??????



23
????? 1.????,???????????gt30(????)
?????????,?????????,??
???????
2.???? 3.????
?????????????(?10ANLL)
????gt30
??????????????,???,?????,??
????(??,??,??),????

?,????????? Auer??????????????,???,????
?
?
?



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??????????????????
32
????? ?????????? ??
???
T?? B??
33
?????????? ??????????Chromosome?Gene???
?M3 t(15i17) (q22q21)
PML RARa ??PML/RARa????
???????N-ras??????,??,????P53?
Rb??


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???????(CFU-GM) ????? ???(ANLL)CFU-GM
??????????,?? ???????????
???????? ???????? ??????(??????)
???? ,??????? DIC????????
????????? M5
??
?????
CNS-L??????,?????????????
WBCgt0.01109/L ???
(gt450mg/L) ???
??????????
?



?


?
?

?
?
41
??????? ?? ???? ??
??? ???? ???????????(MDS)
RAEB RAEB-T ??????,????lt30



42
?????????????? ????(?????????),???????
??? ? ,???,??? ???
?????????? ?? ?????????????????,????PAS(-
) (??M6??) ??AA?ITP
???????? ??????????????
????????????????? ????????Auer??,??????(??
???) PLT??,??????????????
????
???? (????),????,???
43
?? ?????? (?)???? 1.?????????????,???????????
?? ???
?????????????,?????
????????X?,?????,????????? ???????????
???????????????? ????????????
????????????a(IFN-a)? G-CSF?GM-CSF
????? ??








44
2.?????? ????,???? ????????????
???B4 ??? ??? (?)????
??/?RBC,?????????????????? (?)????
PLT?? ?PLT DIC????
??????????




??
45
(?)????????? ?????????? ?????? ?
?????? ??????? ??
??
??????
??????????,????0.1 Tid PO
?????????????? (?)????
??????????????,???????, ?????
46
?????? ??? ???60-85
???????30-40
? ? ???72-77

???????50 (?)???????,??,??,??????
????????????? ???? 1.???????
2.?? Hb
100g(?)?90g/L(????)
?????? 1.5109/L
PLT 100109/L

???WBC????????
3.??? ?????
????
????
??
???
5
??
47

??????????,??????,???? ???? ????????????
???????????,????????????
??????????,???????? (?)?????????? 1.??
?? ??VP??,??????80-90
??VP??,?????50
VLP VDP
VDLP
??ALL??????????,????????3-4? ??????????????

???72-77.8


48

• ????
• ??????????VDLP???????(VCR)2mg,????,?1,8,15,22??DN
  R 4060mg/(m2d),????,?13?????????(L-Asp)6
  000u/(m2d) ,????,?1728?????(Pred)3040mg/(m2d),
  ??,?128???14????,???????????,??????,??DNR
  4060mg/(m2d),????,?1516?,?28?????,?????,??1014
  ?,???2???

49
2.???????????????6???
1.4 ????????
2.5 ???????(VP-16)Arc-C
3.6 ??????????,??12h
???????
??ALL????????????/?????? 3.??????????,?????
,3-5?? ??????????? ???????????
?????Ara-C(???????)


50
(?)ANLL????????????????,????
?? 1.?????? DA???85
HA???85
HOAP???85 M3
???,?????85 ????????65-98 2.
???? ????????4-6??
????Ara-C ????????????(VP16?
???) ???1-2????1?,??1-2?,??????,????
??????????????????
51

• ???? DA?? ?????(DNR)4060mg/(
  m2d),????,?13??????(Ara-C)100150mg/(
  m2d),????,?17?,??2?,??12???,6070????????(CR)
  ? HA?????????(H)24mg/ (m2d),????,?17??Ara-C
  100150 mg/( m2d),????,?17???CR??60,???DA???
  MA???????(NVT)510mg/( m2d),????,?13??Ara-C
  100150 mg/( m2d),????,?17???????????????????,??
  ??????

52

• ????????????? ?FAB????????????(acute
  promyelocytic leukemia,APL)??AML-
  M3??????????????????????Auer??(????????)?????????
  ??????????,????DIC????????90?????????????t(151
  7)?????(?????????5),??????,????????

53

• 1986?????????????????????(all-trans
  retinoid acid,ATRA)??APL????,???????????APL???????
  ?? ATRA???????????????????????????????????????????
  ????????????????????????(RAS),???ATRA?228?,??????
  ???????????????????????????????,???????????????,??
  ???????????????????????ATRA????ATRA???????????????
  ????????? ?

54

• ?????(As2O3)??????????????.???????????????
  ??????.??????,????????As2O3????????????(APL)??????
  ,??SFDA?1999?????As2O3???????,??FDA??2000???As2O3?
  ?????????APL??????.??????????,As2O3???APL??????

55
(?)?? ??????????? ? ????
MDS-RAEB-T ???????
?????? ?????????????? ??
?????????Ara-C???/DNR/????/ VP16
???Ara-c?Hom ivdrop????
56
???????????(CNS-L)?? CNS-L????????,?????
? ?????????????10mg,2?/w, ?3?
??MTX10-15mg/?,2?/w,?????????
??????? ??5mg-10mg,1?/6-8w,??
?????????
?MTX????,???Ara-c,??????
?????????(?????)
MTX????????????????? ???????????
????????,????????
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??????(bone marrow transplantation, BMT)
??????????????????,???????????????????????????????
??????? ??????(autologous BMT, ABMT)
?????? ???BMT(allogeneic
BMT,allo-BMT)
???BMT(syngeneic BMT,syn-BMT)
????
58
????????????????,???CR1??BMT?,??AL???HLA??
???????????CR1???allo-BMT,??lt50???
59

1990,E. D Thomas ?????(allo-BMT????)
BMT ?????,???,????????
???????????, ?AL????????????? allo-BMT
???????????????????
?? GVHD,????? syn-BMT
???GVHD,????,????
???????????,????,???



60

???????????1990?? ALL 7?????48 2
ANLL7?????44 5 ??????? allo-BMT
syn-BMT
ABMT
blood stem cell transplantation, BSCT
cord blood stem cell
transplantation,

CBSCT

61
?? ?????AL?????3?? ALL 1-9y???
lt1y/gt9y/???/?????
gt60y???? ANLL??????
??????? WBCgt50109/L
PLTlt30109/L
Chromosome 5-, 7-,
5q-, 7q-/????
t(922) ? ALL
???????AL
MDS-RAEBT-? AL
????
??????C? ???????????
??? M3 t(821),
inv(16), 21