bone marrow transplantation 3rd pan-european conference on haemoglobinopathies & rare anaemias...
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Bone Marrow Transplantation
3rd Pan-European Conference on Haemoglobinopathies & Rare Anaemias
Limassol, 24 – 26 October 2012
Lawrence FaulknerCure2Children Foundation-Italy
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 ThalassemiaStandard 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
OS TFS
Class 1 94% 87%
Class 2 84% 81%
Class 3 70% 58%
Patients < 17 year
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)
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%
Quality of life post-BMT
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 transplant-related 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 fibrosisErer et al. Bone Marrow Transplant.,1994;14(3):369–372Angelucci 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
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
ThalassemiaPakistan vs. UK
UK Pakistan
Prevalence 700 60.000
New cases/year 30 5.000
Age Groups
0-10 years : 75.6%11-20 years: 24.1%21-40 years: 0.3%
Thalassaemia statistics in Pakistan
0
20
40
60
80
100
120
2 4 6 8 10 12 14 16 18 20 22 24 25
1996
2006
1996: data from HBB Karachi, 2006: data from BTIHS, Karachi
Thalassemia survival in Pakistan
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.
Ayesha 8 y/o with thalassemia transplanted in Italy
Pakistan
BMT for thalassemia
Irfan M et al., JPMA 2008 60%
Infections? Skills? Patient selection? Family support?
Lucarelli G at al., 500 class 1-2 pts 85%
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
JaipurRajhastan-India
Bone marrow and stem cell transplantationA global perspective
Outcome of the first 12 low risk patientsage <6 y, liver <2cm, matched sibling donor: 6 at PIMS-Pakistan 6 at SEAIT-Jaipur
92% cure
Bone marrow and stem cell transplantationA global perspective
Construction & Renovation
Furniture & Equipments
Total
PIMS Pakistan 11,000$ 24,000$ 35,000$
SEAIT India 135,000$ 29,000$ 164,000$
Bone marrow and stem cell transplantationCosts (low-risk, compatible sibling)
Indirect positive effects of BMT
Increases awareness about thalassemia
Attracts families for screening
Generates resources for supportive care and prevention
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 transplantationThalassemia 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%
Medical therapyChelation effective but
expensiveHydroxyurea inexpensive
but partially effective
Quality of life Potentially good Variable
Life expectancyHighly dependent on
medical carePotentially good with modest
care
Prospects
Partially matched related (haploidentical) BMT for sickle cell disease
Mortality III-IV GVHD Graft failure
Haplo BMT (14 pts: 15-42 yrs)
0% 0% 43%
Bolanos-Meade et al. Blood 2012;118:282
Prospects
Double unrelated cord blood vs. Haploidentical marrowResults of 2 parallel phase 2 trials (adult leukemia/lymphoma pts )
1-yr non-relapse
mortality
d100II-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
