What about stem cell transplantation?

Dr Catherine FlynnConsultant Haematologist St James’s Hospital17/06/2011

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 MDSCurrent transplant activity in MDS

EBMT EBMT

2008:2008:– 1147 allografts for MDS ~ 10% of total 1147 allografts for MDS ~ 10% of total

1998-2006 1998-2006 – 1333 MDS patients > 50yrs allografted1333 MDS patients > 50yrs allografted

Types of transplant

Autograft Allogeneic Syngeneic

Myeloablative/traditional Mini-transplant/reduced intensity

MA Allogeneic 2009:Disease Indication

ALL33%

AML 26%APML

3%

CML5%

Lymphoma11%

Myelofibrosis 3%

SAA 3%

MDS 16%

ALL n=13

AML n=10

APML n=1

CML n=2

Lymphoma n=4

MDS n=6

Myelofibrosis n=1

SAA n=1

RIC Allogeneic Transplants 2009:Disease Indication

AML 38%

Waldenstroms5%

Myelofibrosis 5%

Multiple Myeloma 5%

Hodgkin's Disease 5%

MDS 5%

CLL 16%

Lymhoma 21%

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 Disease FactorsPatient Wishes + Support StageAge and Performance MRDCo-Morbidities Previous TreatmentTransfusions/Iron Status Indolent/ProliferativeInfection 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

.

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

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

Performance Score

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

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….

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

Myeloablative Vs Reduced Intensity

High TRM

Low relapseLow TRM

Higher relapse

Transplant Complications

Immune Recovery

Mackall et al BMT 2009

Questions……