12015.8.9. 27 1 PPA
M5
undifferentiatedALL
stem cell
CFU-GEMM
CFU-GM
BFU-E
CFU-Meg
pre-pre-B pre-B immature B mature B
pre-T early-T
M0
M4
CNL M2 M3M1
M6
M7
Common ALL
common-T
preT-ALL T-ALL
BB
LymphomaLymphoma
MyelomaMyeloma
CMLCMLMDSMDS
Leukemia(ALL)Leukemia(ALL)
Leukemia(AML)Leukemia(AML)
CLLCLL
FAB 1982 1994
Revised Rappaport’s/WHO/Lukes-Collins/Kiel 1976
Working Formulation (WF) 1982~1988
REAL 1994
WHO Jaffe ES et al 2001
/
2008 10Ver.4
VIII®
FS®
®IX®
®
DNA,RNA
<1> DNADNA
6-
2) DNA
<2> .
SIADH
<3> L-
L-
( 40%)WBC MPO
t(8;21), inv(16),t(15;17) ( 70%)t(15;17) M3
: ( A )® ®
( 40 50%)FLT3-ITD NPM1
JALSG ALL93 33%
•Clonal evolu�on
Ph
• de novo
••
(5-Year 93%)
IFN or SCT 2nd line (5-Year 71%)
IFN or SCT (5-Year 63%)
IFN (5-Year 53%)
(5-Year 38%)
16
IFN:SCT
Type 1 Type 2
T315I
TKI
ABL
TKI
3rd TKI Abl, SrcT315I V299L
2nd TKIImatinib ABL
NEJM 354 2542-2551, 2006
Src screeningATP
ImatinibImatinib 325NEJM 354 2531-2541, 2006
Kumar SK. et al. Blood 2008; 111: 2516-2520
M 3g/dl10
No Yes
And
• 1960••
–
• 2008 10– TERMS
• Immunomodulatory drugs (IMiDs)•
–
–• 2010 7
– RevMate
4
• 26S• I B NF- B•
–• 2006 10
Immunomodulatory drugs (IMiDs)••
–
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CD20 )C5
CCR4
IL6CD33
CD30
CD20
CD30 internalization
CD33
calicheamicin
CD33
CD30
CD20
MMAE
ALCL
.
2001 9Pathol Int 2000;50:696-702.
Coiffier B et al. N Engl J Med 2002;346:235-24210 Blood 2010; 116:2040-2045
anti-CD20 McAb - 90Y Ibritumomab Tiuxetan
(Zevalin ) 2008
43.5%
24.6%
PNH
Flower Cells
.
CCR4
AZT 19771985 1990
2015 ~( )
19831986 1991
2010
R-CHOPDay 1 2 3 4 5 6
Rituximab 375 mg/m2 (div)
CY 750 mg/m2 (div)
DXR 50 mg/m2 (div)
VCR 1.4 mg/m2 (max 2mg) (iv)
PSL 100 mg/body (po)
PEG-G-CSF
2 5
PEG
Metcalf D., Nature 1994;364:519
Stem Cells 16: 322-328, 1998
~70kDa
332 (TPO exon intron3q27-28
Malignant mesothelioma
IL-6
(Plt=170 )
Higashihara M, et al: Cancer 70: 2105-2108, 1992
STAT PP
RAS/RAF
MAPKK
p42/44
SOSSOS
GRB2
P P
JAK
SHCTPO
TPO
PI3K
AKT
J. Cell Biol. 147:1299, 1999
WF
ITPStandardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children:report from an international working group
---------------------------------------------------------------------------------------------Idiopathic (immune) Thrombocytopenic Purpura (ITP)
ImmunePurpura
Immune Thrombocytopenia (ITP)primarysecondary i.e. secondary ITP(lupus-associated)
lupus-associated ITP
Blood 2009;113: 2386
Kurata Y, et al. Int J Hematol 93:329, 2011
2004~2007 7,774
130
56
1. 22,853
2. 9,4793. 1,192
201253:433-42, 2012
ITP
NEJM 355:1672, 2006
mpl Fc
~60kD
Increased platelet destruction ( )Anti-platelet immunity
Anti-megakaryocyteimmunity
Decreased platelet production
( )
A•
Kumagai Y, et al. J Clin Pharmacol 2007;47(12):1489-97.
• Shirasugi Y, et al. Int J Hematol, 2009
• 3Miyazaki K, et al. (ASH, 2010; EHA, 2011 )Shirasugi Y, et al. Int J Hematol 2011; 2012
0.3, 1, 2μg/kg 1μg/kg
1μg/kg 4/8 1.5 2μg/kg 3/8 1.5 3/8 2TPO ( 2005 )
Romiplostim
2010 12 28
2011 1 21
2008
1~10μg/kgic
2010 12 10
200812.5~50mg/body
: 546
ITP
H.Pylori
First line
Second line
Third line
H.Pylor
i(+)
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201253:433-42, 2012
2. Metronidazole 500mg 2x
2010 6 18 ITP3
H.Pylori
2005 69%(300/435)63%(103/163)
(
48