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Company LogoZHONGHONG SHAO, MDChina
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 HospitalSHAO Zong-Hong
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Company LogoAA
Epidemiology
Pathogenesis
Treatment
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Company LogoEpidemiology
1986~1989
24 Provinces
600,000
0.74/10 5 , higher incidence than Western
countries
No gender difference
At any age
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Company LogoAA
Epidemiology
Pathogenesis
Treatment
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Company Logo 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 decreasedIn 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 MLRlymphocyte 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
nCD8+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*#
RemissionSAA
15 5.19±4.29 2.98±1.35 20.65±5.38 12.02±3.03#
NormalControl
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
Chinese Journal of Hematology,2011,32(9):597-601.
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CD8+CD25+T cell
8. 511. 78
1. 86
96. 0885. 2
82. 0972. 11
34. 38
17. 92
94. 25
51. 2
32. 91
0102030405060708090
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. 268. 34
100
54 56. 85
100
65
50
0102030405060708090
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
Chinese Journal of Hematology,2012,92(18):1240-1243.
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 patientsR3: 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
PerforinGranzyme
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Company LogoAA
Epidemiology
Pathogenesis
Treatment
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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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Company LogoExpert Consensus
IST HSCT
Lack of a matched donorATG Plus CSA
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Other countries
Response rate 7O %~ 8O%
China
Response rate 76.7%
Chinese Journal of Hematology,2001,22(4):177-181.
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 survivalFAA :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
MinorRecovery
No Response
Effect of IST in Our Hospital
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Company LogoGranulocyte Transfusion Combined with Granulocyte Colony Stimulating Factor
PLoS ONE 9(2): e88148. doi:10.1371/journal.pone.0088148
EfficacyGranulocyte 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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Company LogoGranulocyte Transfusion Combined with Granulocyte Colony Stimulating Factor
PLoS ONE 9(2): e88148.
Fig.Response of SAA patients receiving granulocytes and G-CSF therapy.
EfficacyGranulocyte transfusions + G-CSF = an adjunctive therapy for treating severe infections of patients with SAA
•Response Rate
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Company LogoGranulocyte Transfusion Combined with Granulocyte Colony Stimulating Factor
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 byantipyretics 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.
Chinese Journal of Hematology,1996,17(4):176-178.Chinese Journal of Hematology,2001,22(4):177-181.
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Company LogoComplication of Infection
Chinese Journal of Hematology,2003,24(10):530-533.
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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