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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? 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
Incidence LRF;Leeds UK
MDS transplant Activity Increase in the number of reduced intensity transplants Increase in the number of unrelated donor transplants Increase in patients >50 years
Current transplant activity in MDS EBMT 2008: 1147 allografts for MDS ~ 10% of total 1998-2006 1333 MDS patients > 50yrs allografted
Types of transplant • Autograft • Allogeneic • Syngeneic • Myeloablative/traditional • Mini-transplant/reduced intensity
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
Curative Potential Mc Clune et al JCO
Outcomes (Kroger MDS ESH meeting) • Survival without relapse 29-40% • Mortality without relapse 37-50% • Relapse 23-48%
Early Consideration of Transplant • Potential candidates should have a donor search and be referred for discussion
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
. 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
Co-Morbidities • Lung problems • Liver problems • Joint/Bone problems • Psychiatric disorders • Previous other cancer • Stomach Ulcer • Brain/stroke illness
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
Low Risk MDS High Risk MDS Disease Stage
Chromosomes Count….. 46, XY [80%] 46, XY, del (5q)(q11q33), del (7q)(q11q36) [20%].
High Ferritin pre transplant is associated with a poor survival
To make a treatment decision or a risk assessment in any patient…. • Patient factors • medical co-morbidity • Disease Factors • Cytogenetics, Transfusion/Iron, WHO subtype
Impact not yet known…… • Timing of Transplant • Chemotherapy before HCT or not ?
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
What to do?? • IPSS score = 0, WPSS =1 • Low risk MDS • No sibling donor • Defer transplant at present
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
What to do? • IPSS= 0.5, WPSS =1 • Low risk MDS • Defer transplant at present
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
Mrs C • 46 year old woman • Presented June 2008 Hb 7, WCC 3, Plats = 53 • Bone marrow 7% blasts • Complex karyotype • No sibling donor
What did we do? • IPSS Int-2 • Unrelated donor search started • 2 courses of chemotherapy • Unrelated transplant May 2009 • Some minor liver GVHD
Unfortunately…. • Died May 2011 with pneumonia • Delayed immune recovery
High TRM Low relapse Low TRM Higher relapse Myeloablative Vs Reduced Intensity
Immune Recovery Mackall et al BMT 2009