1. G. S / AIH 2006 Aplastic anemia; treatment options Gérard Socié, MD PhD Hospital Saint Louis

2. G. S / AIH 2006 Aplastic anemia; treatment options SAA Hypo cellular marrow (<30%) & at least 2/3 criteria: ANC <0.5x10 9 /L Platelets <20x10 9 /L Reticulocytes <20x10 9 /L v.SAA ANC <0.2x10 9 /L moderate AA not fulfilling criteria of SAA ANC >0.5x10 9 /L

3. G. S / AIH 2006 Aplastic anemia; treatment options Megaloblastic proerythroblast, coarse chromatin, multiple nucleoli cytoplasmic budding Dysplastic changes in the myeloid series Dysplastic changes in the few scattered hematopoietic cells Hemophagocytosis by an immature myeloid cell MDS or SAA? Fibrosis Splenomegaly Blasts Dysplastic megakaryocyte myeloid Cytogenetics? PNH?

4. G. S / AIH 2006 Aplastic anemia; treatment options Does this guideline hold true?

5. G. S / AIH 2006 Aplastic anemia; treatment options Ades et al. Blood. 2004;103: 2490-2497 HSCT HLA-id. Sibling D

6. G. S / AIH 2006 Aplastic anemia; treatment options 5 year Survival <1985: 51% + 4 n= 741 1985-94: 63% + 2 n=1384 1995-04: 69% + 2 n=2044 Better outcome - early BMT - few transfusions - age - GvHD prophylaxis CSA+MTX

7. G. S / AIH 2006 Aplastic anemia; treatment options Cy - TAI Cy - ATG Time from transplant (year)

8. G. S / AIH 2006 Aplastic anemia; treatment options

9. G. S / AIH 2006 Aplastic anemia; treatment options Immunosuppression 10 years 5 years -77±8%160>2000 69±4%73±3%1114 1990- 2000 61±5%67±5%413 1980- 1990 46±4%54±4%577<1980 SurvivalNTime period

10. G. S / AIH 2006 Aplastic anemia; treatment options Bacigalupo A. Blood 2000; 95(6):1931-1934. Immunosuppressive treatment Best results with ATG + CSA

11. G. S / AIH 2006 Aplastic anemia; treatment options Bacigalupo A, Blood 2000; (95). 1931-1934 Frickhofen N. Blood. 2003 (101). 1236-1242 Socié G. NEJM. 1993; (329). 1152-1157

12. G. S / AIH 2006 Aplastic anemia; treatment options Socié G. et al., Submitted 2006

13. G. S / AIH 2006 Aplastic anemia; treatment options UD transplant < 1998 > 1998 SFGM-TC

14. G. S / AIH 2006 Aplastic anemia; treatment options SFGM-TC In multivariate analysis: survival -HLA allelic matching (P<.01) - younger age of (<17 years, P<.0001). Survival reached 78%±11% at 5-year for the younger patients HLA-matched.

15. G. S / AIH 2006 Aplastic anemia; treatment options Identical sibling As early as possible Bone marrow Cy + ATG CSA +MTX MUD after failed IS 1 - 2 courses? Conditioning? GvHD Prophylaxis?

16. G. S / AIH 2006 Aplastic anemia; treatment options BMT good results with Id Sibling BMT MUD BMT (2nd line) Older (Age old??) Alternative donors? Cord? IS good results with H-ATG + CSA G-CSF still need randomized trial no upper age limit refractory patients? other immunosuppressant? MMF ineffective Campath? Sirolimus? Anti-CD25? Rituximab?