Non-Transplant Therapies Aplastic Anemia.

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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


Company LogoAA

Epidemiology

Pathogenesis

Treatment


Company LogoEpidemiology

1986~1989

24 Provinces

600,000

0.74/10 5 higher incidence than Western

countries

No gender difference

At any age


Company LogoAA

Epidemiology

Pathogenesis

Treatment


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


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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


Company LogoDentritic Cell (DC)

mDC 0.290.10 pDC 0.290.13

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 322.13171.07* 2 SAA SAA 320.25161.90 3 normal normal 192.2591.934 normal SAA 182.50147.79

*Group 1 vs Group 3 P


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 3.672.58 2.251.35 39.308.13*# 27.817.10*#

RemissionSAA

15 5.194.29 2.981.35 20.655.38 12.023.03#

NormalControl

12 4.842.31 2.111.88 18.346.68 8.502.33

*SAA vs Remission Group p


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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

Fas TNF-

SAASAA

35. 42

7. 69

23. 34

93. 21

69. 268. 34

100

54 56. 85

100

65

50

0102030405060708090

100

Fas TNF-

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 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


Company LogoPathogenesis of AA

PerforinGranzyme


Company LogoAA

Epidemiology

Pathogenesis

Treatment


Company LogoExpert Consensus

IST HSCT

Lack of a matched donorATG Plus CSA


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IST HSCT


Expert Consensus


Company LogoExpert Consensus

IST HSCT



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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 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%

Overall response rate 83.9%

Complete responders

Partial responders

MinorRecovery

No Response

Effect of IST in Our Hospital


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.



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



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.


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.


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.


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.

Education

artcom pt

journal of clinical

krcompany logoepidemiology

saa saa

saa normal

normal saa

mdchina head of hematology

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