Slide สอน R med เรื่อง aplastic anemia and bone marrow failure

1. Aplastic anemia
• approach
–
–

2. Diagnosis
• Pancytopenia • Exclude
• Hypocellular marrow – Acute leukemia
– Aspiration – Myelodysplastic
– Biopsy syndrome
– Paroxysmal nocturnal
hemoglobinuria

3. Bone marrow pathology

5. aplastic
anemia
• exposure to
– nonbottled water
– certain animals (ducks and geese)
– animal fertilizer
– pesticides

6. aplastic anemia
historical studies
• Drugs
• Chemicals
• Pregnancy
• Eosinophilic fasciitis
• Hepatitis - seronegative

7. • occupational exposure
•
•
• bone
marrow transplantation)

8. Proper Investigations
• CBC, blood smear
• Bone marrow aspiration and biopsy
• Chromosome study (in elderly patients)
• PNH work up
• Hepatitis viruses
• Complete blood typing

9. Severe Aplastic Anemia
Peripheral blood
• Granulocyte < 500/mm3
• Platelet < 20,000/mm3
• Reticulocyte count < 1%
Bone marrow
• Cellularity < 25%
• Cellularity 25-50% hematopoietic cells <
30%

10. Aplastic anemia is an immune process
• What else could be so effective and
selective?

11. aplastic
anemia immune process
• clinical
– Autologous recovery after stem cell
transplantation
– Failed syngeneic transplantation
– Response to immunosuppresion
• lab
– Lymphocyte co-culture

12. Cell , cytokine
mechanism
• Th1 lymphocytes

13. Proximal events in immune-
mediated marrow failure

14. Apoptosis
• apoptosis stem cell
• upregulation gene
apoptosis
• cell expose
gamma interferon

15. mechanism
AA PNH
• “Escape” from immune process
GPI-linked membrane proteins

16. MDS presentation respond to
treatment AA mutation
• Trisomy 8
• Upregulation anti-apoptosis genes

17. Management of Severe AA
• BMT or ATG or
> 70%
• Antithymocyte globulin
– Better results when combined with cyclosporin
– Anticipated response > 3
• Allogeneic bone marrow transplantation, esp.
in
– Young patient
– Patient with very severe AA

18. Results of BMT in AA (from
NMDP, USA)

19. BMT AA
2
• Chronic GVHD
– Irradiation
– Heavy cell dose
– Increasing age
• Rejection
– Heavy previous transfusion
– Low cell dose

20. long tem surivival AA
ATG CsA 3 11
• 3 65-70%
• 11 39%

21. Risk relapse ATG CsA
• 30 – 40 %
• prolonged CsA (> 6
months)

22. Long term CsA dependence
ATG CsA
• 26-62%

23. role additional G-CSF
ATG CsA
• neutrophil
trilineage hematological recovery
survival

24. ATG
•2
• response 50-60%
• relapse

25. Management of non-severe
AA
• Anabolic hormones
– Anticipated response > 3
• Cyclosporin alone

26. supportive
treatment
• AA
•
• Decreased quality of life
• Loss of work opportunity
• High expense of treatment

27. Transfusion guidelines
• BMT
• leukodepleted blood products
• Platelet transfusion
Prophylactic vs. Therapeutics