Bone Marrow Transplantation
3rd Pan-European Conference on
Haemoglobinopathies & Rare Anaemias
Limassol, 24 – 26 October 2012
Lawrence Faulkner
Cure2Children Foundation-Italy
lawrence.faulkner@cure2children.org
Bone marrow and stem cell transplantation
BMT in the “new thalassemic” era
 Mortality and morbidity
 Quality of life
 Cost-effectiveness
 Global perspective
Risk Classes for BMT in Thalassemia
Standard preparation with Busulfan-Cyclophosphamide (BuCy)
Chelation
Hepatomegaly
Fibrosis
Class 1
Regular
No
No
Class 2
Reg/Irreg
No/yes
No/Yes
Class 3
Irregular
Yes
yes
Patients < 17 year
OS
TFS
Class 1
94%
87%
Class 2
84%
81%
Class 3
70%
58%
Adults
OS
TFS
67%
63%
Emanuele Angelucci: Hematopoietic stem cell transplantation for Thalassemia. ASH Educational Book 2010
Bone marrow and stem cell transplantation
Late effects
 Infertility
 Delayed puberty (females)
•
Impaired growth and development (TBI)
•
Second malignancies (TBI)
•
Intellectual impairment (CNS-directed therapy)
Quality of life post-BMT
Caocci G, et al. EBMT 2012: P1034
54 patients (26 females and 28 males) after a mean of 20
years from sibling donor BMT compared to 41 sibling donors.
Mean age at BMT 14 yrs (currently 38 yrs) and 18 (currently
41 yrs) for patients and donors, respectively. Chronic graft
versus host disease reported in 18.5%.
Patients had lower QoL scores for vitality, physical & social
functioning
Patient
Donor sibling
Working
67%
80%
Living with spouse/partner
40%
61%
Had babies
15%
31%
Bone marrow and stem cell transplantation
Splenectomy and BMT
 Enlarged spleen per se is not associated with higher
rejection rates
 May increase transfusion requirements and delay
engraftment
 Splenectomy may be associated with increased transplantrelated mortality. Mathews et al. Pediatr Transplant. 2009;13(2):171–176
Bone marrow and stem cell transplantation
Hepatitis C and BMT
 No evidence that BMT has any influence on the course
of HCV infection or vice versa.
 Hepatitis C and iron overload may accelerate
progression of liver fibrosis
Erer et al. Bone Marrow Transplant.,1994;14(3):369–372
Angelucci et al. Blood, 2002;100(1):17–21
HCV positivity may thus actually strengthen the indication
for BMT if proper supportive care is not available
Bone marrow and stem cell transplantation
Cost-effectiveness
A cost-utility and budget impact analysis of allogeneic
hematopoietic stem cell transplantation for severe
thalassemic patients in Thailand
Leelahavarong et al. BMC Health Services Research 2010, 10:209
(http://www.biomedcentral.com/1472-6963/10/209
Bone marrow and stem cell transplantation
A global perspective
Thalassemia in Pakistan
• Thalassemia carriers
5% population
• Total Carriers
8 million
• Thalassaemia births/year
5,000 – 6,000
• Thalassaemia Major prevalence
~ 60,000
• ~ 4% national health budget goes to thalassemia
care (for appropriate management it would have to increase to
40%).
• Thalassemia is the main donated blood consumer
Thalassemia
Pakistan vs. UK
Prevalence
New cases/year
UK
700
30
Pakistan
60.000
5.000
Thalassaemia statistics in Pakistan
Age Groups
0-10 years : 75.6%
11-20 years: 24.1%
21-40 years: 0.3%
Thalassemia survival in Pakistan
120
100
80
1996
2006
60
40
20
0
2
4
6
8
10 12 14 16 18 20 22 24 25
1996: data from HBB Karachi, 2006: data from BTIHS, Karachi
Mission
Cure2Children (C2C) is a non-profit, apolitical, and
secular organization providing support for the care of
children with cancer and severe blood disorder in
developing countries.
Pakistan
Ayesha 8 y/o with thalassemia transplanted in Italy
BMT for thalassemia
Lucarelli G at al., 500 class 1-2 pts
85%
Irfan M et al., JPMA 2008 60%
Infections? Skills? Patient selection? Family support?
Objectives of the Pakistan project
1.
> 80% cure il low-risk patients with a matched sibling
2.
Increase awareness and access to cure, screening and prevention
Prospective (clinical management-oriented) database
Computerized treatment plans (Excel format)
Local personnel
Jaipur
Rajhastan-India
Bone marrow and stem cell transplantation
A global perspective
Outcome of the first
12 low risk patients
age <6 y, liver <2cm,
matched sibling donor:
 6 at PIMS-Pakistan
 6 at SEAIT-Jaipur
92% cure
Bone marrow and stem cell transplantation
A global perspective
PIMS Pakistan
SEAIT India
Construction &
Renovation
Furniture &
Equipments
Total
11,000$
24,000$
35,000$
135,000$
29,000$
164,000$
Bone marrow and stem cell transplantation
Costs (low-risk, compatible sibling)
Blood products
Hospital charges
Surgical
Pharmacy
Professionals
$1,700
$200
$600
$300
$2,100
$4,600
$900 $10,700
India
(SEAIT)
$500
$2,500
$200
$3,100
$1,800
$4,600
$1,200
$900 $15,000
Total
Diagnostics
$400
Follow up
Pre-BMTevaluation
Pakistan
(PIMS)
Indirect positive effects of BMT
 Increases awareness about thalassemia
 Attracts families for screening
 Generates
prevention
resources
for
supportive
care
and
 Increase compliance with chelation and use of safe
blood
 Attracts and motivate professionals
 Empowers medical centers and paves the way for the
cure of related disorders
Accessible HLA screening
Poster session, El Missiry et al.: HLA-typing by buccal swab to facilitate
acees to bone marrow transplantation globally. Abstract book page 104
Bone marrow and stem cell transplantation
Thalassemia vs. Sickle cell disease
Thalassemia
Sickle cell disease
New cases/year
> 80,000
> 250,000
Total BMTs done
~ 3,000
~ 300
Risk group
identification
Good
Poor
Transplant related
mortality
5-40%
5-10%
Chelation effective but
expensive
Hydroxyurea inexpensive
but partially effective
Potentially good
Variable
Highly dependent on
medical care
Potentially good with
modest care
Medical therapy
Quality of life
Life expectancy
Prospects
Partially matched related (haploidentical)
BMT for sickle cell disease
Haplo BMT
(14 pts: 15-42 yrs)
Mortality
III-IV GVHD
Graft
failure
0%
0%
43%
Bolanos-Meade et al. Blood 2012;118:282
Prospects
Double unrelated cord blood vs. Haploidentical marrow
Results of 2 parallel phase 2 trials (adult leukemia/lymphoma pts )
1-yr nonrelapse
mortality
d100
II-IV
GVHD
Median
ANC
recovery
(>500)
Median
plt
recovery
(>20K)
Graft
failure
Stem cell
source
cost
dUCB
(50 pts)
24%
40%
d15
d30
12%
>60.000$
Haplo BMT
(50 pts)
7%
32%
d16
d24
2%
0
Brunstein et al. Blood 2011;118:282
The role of third-party international professional
organizations
 Foster the use of common protocols and procedures
 Reassure patients and professionals in the early phase
 Decrease unnecessary expenses
 Increased scientific visibility
 Support fund-development
 Provide network referrals
 Promote screening and prevention
Bone marrow and stem cell transplantation
Conclusions
 BMT outcomes are improving in parallel with supportive and thus
indications in severe thalassemia are still controversial, at least in
affluent countries
 In thalassemia-prone regions where appropriate long-term supportive
care might not be readily accessible and resources limited, BMT is
feasible, cost-effective and can save lives.
 Thalassemia associations, NGOs and professional networks may play
an important role to promote non-profit and ethical BMT programs
 In emerging countries better access to BMT may increases hope and
thus improve compliance with supportive care
 BMT programs may increase awareness, attract professionals and
promote prevention
Thank you
lawrence.faulkner@cure2children.org