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What about stem cell transplantation?

What about stem cell transplantation?. Dr Catherine Flynn Consultant Haematologist St James’s Hospital 17/06/2011. What is Myelodysplasia?. Stem cell disorder with a variable clinical course Treatment strategy with the highest curative potential is an allogeneic stem cell transplant.

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What about stem cell transplantation?

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  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: 1147 allografts for MDS ~ 10% of total 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

  9. 25 years of BMT in Ireland

  10. Decision to Transplant Patient Factors Disease Factors Patient Wishes + Support Stage Age and Performance MRD Co-Morbidities Previous 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 relapse 29-40% • Mortality without relapse 37-50% • Relapse 23-48%

  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. . 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 Cutler C S et al. Blood 2004;104:579-585 ©2004 by American Society of Hematology

  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. Low Risk MDS High Risk MDS Disease Stage

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

  36. Transplant Complications

  37. Immune Recovery Mackall et al BMT 2009

  38. Questions……

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