What about stem cell transplantation?
Dr Catherine Flynn
Consultant Haematologist
St James’s Hospital
17/06/2011
What is Myelodysplasia?
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Stem cell disorder with a variable clinical course
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Treatment strategy with the highest curative
potential is an allogeneic stem cell transplant
Incidence
LRF;Leeds UK
MDS transplant Activity
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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
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2008:
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1147 allografts for MDS ~ 10% of total
1998-2006
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1333 MDS patients > 50yrs allografted
Types of transplant
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Autograft
Allogeneic
Syngeneic
Myeloablative/traditional
Mini-transplant/reduced intensity
MA Allogeneic 2009:
Disease Indication
Myelofibrosis
3%
SAA
3%
MDS
16%
ALL
33%
AML n=10
APML n=1
CML n=2
Lymphoma
11%
Lymphoma n=4
MDS n=6
CML
5%
APML
3%
ALL n=13
Myelofibrosis n=1
AML
26%
SAA n=1
RIC Allogeneic Transplants 2009:
Disease Indication
Myelofibrosis
5%
Multiple Myeloma
5%
MDS
5%
Waldenstroms
5%
AML
38%
Hodgkin's Disease
5%
Lymhoma
21%
CLL
16%
AML n = 7
CLL n=3
Lymhoma n=4
Hodgkin's Disease n=1
MDS n=1
Multiple Myeloma n=1
Myelofibrosis n=1
Waldenstroms n=1
Patient Factors
Patient Wishes + Support
Age and Performance
Co-Morbidities
Transfusions/Iron Status
Infection
Disease Factors
Stage
MRD
Previous Treatment
Indolent/Proliferative
Extramedullary Disease
Curative Potential
Mc Clune et al JCO
Outcomes (Kroger MDS ESH meeting)
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Survival without relapse
Mortality without relapse
Relapse
29-40%
37-50%
23-48%
Early Consideration of Transplant
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Potential candidates should have a donor
search and be referred for discussion
Timing Is important……
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Delaying SCT can result in maximising
overall survival for low and intermediate risk
MDS (Cutler et al)
Optimal Timing
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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.
Cutler C S et al. Blood 2004;104:579-585
©2004 by American Society of Hematology
Patients over 60 excluded, MA conditioning only
Co-Morbidities
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–
–
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Lung problems
Liver problems
Joint/Bone problems
Psychiatric disorders
Previous other cancer
Stomach Ulcer
Brain/stroke illness
Performance Score
Biological Age
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Chronological Age
Physical Function
Organ co-morbidities
Ability to withstand the harshness of chemoradiotherapy
To process different medications and large volumes
of fluid
To tolerate serious infections and harmful effects of
GVHD
Disease Stage
Low Risk MDS
High Risk MDS
Chromosomes Count…..
46, XY [80%] 46, XY, del
(5q)(q11q33), del
(7q)(q11q36) [20%].
International prognostic Scoring
System
WHO Prognostic Scoring System
Number of transfusions and iron overload
High Ferritin pre transplant is
associated with a poor survival
To make a treatment decision or a risk
assessment in any patient….
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Patient factors
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medical co-morbidity
Disease Factors
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Cytogenetics, Transfusion/Iron, WHO subtype
Impact not yet known……
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Timing of Transplant
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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 multilineage dysplasia
April 2011 Hb= 8.8g/DL
? Consider Transplant
What to do??
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IPSS score = 0, WPSS =1
Low risk MDS
No sibling donor
Defer transplant at present
Mrs B
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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?
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IPSS= 0.5, WPSS =1
Low risk MDS
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Defer transplant at present
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Update January 2011
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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
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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?
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IPSS Int-2
Unrelated donor search started
2 courses of chemotherapy
Unrelated transplant May 2009
Some minor liver GVHD
Unfortunately….
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Died May 2011 with pneumonia
Delayed immune recovery
Myeloablative Vs Reduced Intensity
High TRM
Low relapse
Low TRM
Higher
relapse
Transplant Complications
Immune Recovery
Mackall et al BMT 2009
Questions……