1. What about stem cell transplantation? Dr Catherine Flynn Consultant Haematologist St James’s Hospital 17/06/2011

2. What is Myelodysplasia? Stem cell disorder with a variable clinical course Treatment strategy with the highest curative potential is an allogeneic stem cell transplant

3. Incidence LRF;Leeds UK

4. MDS transplant Activity Increase in the number of reduced intensity transplants Increase in the number of unrelated donor transplants Increase in patients >50 years

5. Current transplant activity in MDS EBMT 2008: 2008: – 1147 allografts for MDS ~ 10% of total 1998-2006 1998-2006 – 1333 MDS patients > 50yrs allografted

6. Types of transplant Autograft Allogeneic Syngeneic Myeloablative/traditional Mini-transplant/reduced intensity

7. MA Allogeneic 2009: Disease Indication

8. RIC Allogeneic Transplants 2009: Disease Indication

10. Patient Factors Disease Factors Patient Wishes + Support Stage Age and Performance MRD Co-MorbiditiesPrevious Treatment Transfusions/Iron Status Indolent/Proliferative Infection Extramedullary Disease

11. Curative Potential Mc Clune et al JCO

12. Outcomes (Kroger MDS ESH meeting) Survival without relapse29-40% Mortality without relapse37-50% Relapse23-48%

13. Early Consideration of Transplant Potential candidates should have a donor search and be referred for discussion

14. Timing Is important…… Delaying SCT can result in maximising overall survival for low and intermediate risk MDS (Cutler et al) Optimal Timing Time of a new cytogenetic abnormality Appearance of a clinically significant cytopenia Increase in the percentage of bone marrow blasts

15. . Cutler C S et al. Blood 2004;104:579-585 ©2004 by American Society of Hematology Net benefit or loss overall discounted life expectancy for the 4 IPSS risk groups are shown above and below the x-axis. Patients over 60 excluded, MA conditioning only

16. Co-Morbidities – Lung problems – Liver problems – Joint/Bone problems – Psychiatric disorders – Previous other cancer – Stomach Ulcer – Brain/stroke illness

17. Performance Score

18. Biological Age Chronological Age Physical Function Organ co-morbidities Ability to withstand the harshness of chemo- radiotherapy To process different medications and large volumes of fluid To tolerate serious infections and harmful effects of GVHD

19. Disease Stage Low Risk MDSHigh Risk MDS

20. Chromosomes Count….. 46, XY [80%] 46, XY, del (5q)(q11q33), del (7q)(q11q36) [20%].

21. International prognostic Scoring System

22. WHO Prognostic Scoring System

23. Number of transfusions and iron overload

24. High Ferritin pre transplant is associated with a poor survival

25. To make a treatment decision or a risk assessment in any patient…. Patient factors – medical co-morbidity Disease Factors – Cytogenetics, Transfusion/Iron, WHO subtype

26. Impact not yet known…… Timing of Transplant Chemotherapy before HCT or not ?

27. Miss A 24 year old girl referred in 2008 with anaemia Hb=9.7g/DL, normal WCC and platelet count Karyotype normal Bone marrow Refractory Cytopenia and multi- lineage dysplasia April 2011 Hb= 8.8g/DL ? Consider Transplant

28. What to do?? IPSS score = 0, WPSS =1 Low risk MDS No sibling donor Defer transplant at present

29. Mrs B 56 year old lady seen in September 2010 Hb 9.1, platelets 41, WCC 1.2 Normal karyotype Bone marrow refractory cytopenia and ring sideroblasts Not requiring Transfusions HLA matched sibling

30. What to do? IPSS= 0.5, WPSS =1 Low risk MDS Defer transplant at present

31. Update January 2011 Increasing transfusion requirment Bone marrow and karyotype unchanged March 2011 reduced intensity sibling transplant Currently 80 days post transplant with skin and liver GVHD

32. Mrs C 46 year old woman Presented June 2008 Hb 7, WCC 3, Plats = 53 Bone marrow 7% blasts Complex karyotype No sibling donor

33. What did we do? IPSS Int-2 Unrelated donor search started 2 courses of chemotherapy Unrelated transplant May 2009 Some minor liver GVHD

34. Unfortunately…. Died May 2011 with pneumonia Delayed immune recovery

35. Myeloablative Vs Reduced Intensity High TRM Low relapse Low TRM Higher relapse

36. Transplant Complications

37. Immune Recovery Mackall et al BMT 2009

38. Questions……