Non-Transplant Therapies Aplastic Anemia.

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Company LogoZHONGHONG SHAO, MD
China
 Head of Hematology, Department of Tianjin
Medical University General Hospital
 Dr Shao is Vice President of Chinese Society of
Hematology (CSH); Head of Erythrocyte Disease
Working Group and Head of China PNH Registy
Working Group. At Present, Prof. Shao is the vice
President of Hematology Branch of Chinese Medical
Doctor Association; Vice-chairman of Hematology &
Immunology branch of Chinese Society of
Immunology; Head of Clinical Flow Cytometry
Assicuatuib. Standing Committee Member of CSCO;
President of Tianjin Hematology Association;
Associate Editor-in-chief of Chinese Journal of
Hematology; Editorial Broad Member of Chinese
Journal of Practice Internal Medicine, Journal of
Experimental Hematology, Journal of Clinical
Hematology.

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Aplastic Anemia in China
Tianjin Medical University General Hospital
SHAO Zong-Hong

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Company LogoAA
 Epidemiology
 Pathogenesis
 Treatment

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Company LogoEpidemiology
 1986~1989
 24 Provinces
 600,000
 0.74/105
， higher incidence than Western
countries
 No gender difference
 At any age

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High CD3+CD8+ Effector T Cells in BM
Chinese Journal of Hematology,2004,25(10):613-616.
0
10
20
30
40
50
60
%BMMNC
AA Group Control
Group
* P<0.01
*

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The expression of Linker for
Activations of Tcells (LAT)
in PB CD3+T cells of the SAA
patients was higher than
normal controls.
European Journal of Haematology. 2014.
High LAT in Peripheral Blood CD3+T cells

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Company LogoDentritic Cell (DC)
mDC ： 0.29±0.10
pDC ：
0.29±0.13
After IST, the percentage of mDC and pDC decreased
In 6 months, pDC returned to the pre-treatment level;
mDC was 50% of the pre-treatment level
Int J Hematol, 2011, 93(2):156-162.

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Different sources of mDCs and Lymphocyte 1:50 MLR
lymphocyte proliferation rates
Group mDCs source lymphocyte source lymphocyte proliferation
rates （ % ）
1 SAA normal 322.13±171.07*
2 SAA SAA 320.25±161.90
3 normal normal 192.25±91.93
4 normal SAA 182.50±147.79
*Group 1 vs Group 3 P<0.05
mDCs in SAA patients enhanced lymphocyte proliferation
Chinese Journal of Medicine,2009, 48(12):1040-1043.
Dentritic Cell (DC)

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Company LogoEffector T Cell
n
CD8+
CD25+
T cell CD8+
HLA-DR+
T cell
in CD8+
Tcell in CD3+
T cell in CD8+
Tcell in CD3+
T cell
SAA 14 3.67±2.58 2.25±1.35 39.30±8.13*#
27.81±7.10*#
Remission
SAA
15 5.19±4.29 2.98±1.35 20.65±5.38 12.02±3.03#
Normal
Control
12 4.84±2.31 2.11±1.88 18.34±6.68 8.50±2.33
*SAA vs Remission Group p<0.05
#SAA / R-SAA vs Normal Control p<0.05
CD8+
HLA-DR+
T cell was high in SAA patient
CD8+
CD25+
T cell without significant difference

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CD8+
CD25+
T cell
8. 51
1. 78
1. 86
96. 08
85. 2
82. 09
72. 11
34. 38
17. 92
94. 25
51. 2
32. 91
0
10
20
30
40
50
60
70
80
90
100
穿孔素颗粒酶 Fas TNF- β
初治SAA
缓解SAA
正常对照
35. 42
7. 69
23. 34
93. 21
69. 2
68. 34
100
54 56. 85
100
65
50
0
10
20
30
40
50
60
70
80
90
100
穿孔素颗粒酶 Fas TNF- β
CD8+
HLA-DR+
T cell function factors were high in SAA patients
CD8+
HLA-DR+
T cell
Effector T Cell
Granzyme PerforinPerforin Granzyme

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0.11 0.68 0.53
0.37 0.79 0.41
9.62% 13.81% 18.21%
NK cell
SAA Remission SAA Normal Control
The percentage of NK cell was low in PB lymphocyte of SAA patients
R3 ： CD56bright
； R4 ： CD56dim
； R5 ： CD3-
CD56-
CD16+

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PF
63.23% 70.62% 11.17%
PF
63.23% 70.62% 11.17%63.23% 70.62% 11.17%
NK cell express compensated high level of perforin in SAA patient
Chinese Jouranl of Hematology,2011,16:1084-1087.
NK cell
SAA Remission SAA Normal Control

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Company LogoPathogenesis of AA
Perforin
Granzyme

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Company LogoExpert Consensus
IST HSCT
Lack of a matched donorATG Plus CSA

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IST HSCT
Lack of a matched donorATG Plus CSA
Expert Consensus

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 Other countries
Response rate 7O ％～ 8O%
 China
Response rate 76.7%
Effect of IST

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• Horse ATG plus
cyclosporine
 10-year EFS: 95%
 10-year survival with
events ： 65%
(including relapse and
clonal evolution ）
Hematology Am Soc Hematol Educ Program. 2013;2013:76-81.
Fig. Survival after response to
immunosuppression in severe aplastic anemia
Effect of IST

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Br J Haematol. 2011 Jan;152(2):127-40.
For the last 10 years the standard regimen of horse ATG
for SAA results in overall survival rates ranging between
55% and 95%
Effect of IST

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Ann Hematol. 2013 Dec 14.
FAA (fulminant aplastic anemia):
ANC=0 before and after IST
for at least 2 weeks
Overall survival
5-year overall survival
FAA :88.5 %
vSAA:95.8 %
SAA:96.8 %
Effect of IST

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Tr eat ment ef f ect
40%
23%
21%
16%
完全缓解部分缓解稍有效无效
Overall response rate ： 83.9%
Complete
responders
Partial
responders
Minor
Recovery
No Response
Effect of IST in Our
Hospital

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Granulocyte Transfusion
Combined with Granulocyte Colony Stimulating Factor
PLoS ONE 9(2): e88148. doi:10.1371/journal.pone.0088148
Efficacy
Granulocyte transfusions + G-CSF = an adjunctive therapy for treating
severe infections of patients with SAA
•Survival Rate
Fig.Survival of SAA patients received granulocytes and G-CSF therapy.

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PLoS ONE 9(2): e88148.
Fig.Response of SAA patients receiving granulocytes and G-CSF therapy.
Efficacy
Granulocyte transfusions + G-CSF = an adjunctive therapy for treating
severe infections of patients with SAA
•Response Rate

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PLoS ONE 9(2): e88148.
Fig.Adverse effects of SAA patients received
granulocytes and G-CSF therapy.
Safety
•Chills and fever were mild or moderate and successfully treated and prevented in
the follow transfusions by
antipyretics or corticosteroids.
•Dyspnea
•Allergy reaction
•Heart failure
old patients
relative quick speed of transfusion,
cured by digoxin and furosemide.
There was no other severe
adverse event associated with
granulocytemtransfusions.

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Company LogoHematopoietic Growth Factors (HGFs)
With HGFs
• Higher response rate higher
(89 .2% vs 63 .9%),
• Lower rates of early infection
(24.3 % vs 55 .3%)
• Lower mortality
(4.0 % vs 16 .7%)
• Shorter duration of
cytopenia and blood
transfusion dependence
• Faster recovery of BM
hematopoiesis.
Without HGFs
With HGFs
The use of HGFs could reduce early infection and mortality rates and improve
the response rates in SAA patients.

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Company LogoComplication of Infection
The prevalence of infection in SAA patients was 86.0%
54.2 %was infected with gram-positive organisms,
40 .0% with gram-negative bacilli
5.8% with fungal infections
The total mortality of SAA patients with infection was 23.1%.
Pulmonary infection and septicemia increased mortality.
GM-CSF/G-CSF therapy reduce mortality.
GM-CSF or G-CSF therapy exerts an assistant role to
antibiotics in controlling the infections.

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Company LogoConclusion
 Critical Diagnostic criteria
 Prompt, adequate, fully, rational combination IST
 Active prevention and control of infections
Improve response rate, decrease relapse

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Non-Transplant Therapies Aplastic Anemia.

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Editor's Notes