Bone Marrow Transplantation 3rd Pan-European Conference on

Haemoglobinopathies & Rare AnaemiasLimassol, 24 – 26 October 2012

Lawrence FaulknerCure2Children Foundation-Italy

lawrence.faulkner@cure2children.org

Bone marrow and stem cell transplantation

BMT in the “new thalassemic” eraMortality and morbidityQuality of lifeCost-effectivenessGlobal 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 TFSClass 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 siblingWorking 67% 80%

Living with spouse/partner 40% 61%

Had babies 15% 31%

Quality of life post-BMT

Splenectomy and BMTEnlarged spleen per se is not associated with higher rejection ratesMay increase transfusion requirements and delay engraftmentSplenectomy 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 BMTNo 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-effectivenessA 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 PakistanPrevalence 700 60.000New 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

19962006

1996: data from HBB Karachi, 2006: data from BTIHS, Karachi

Thalassemia survival in Pakistan

MissionCure2Children (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 diseaseNew cases/year > 80,000 > 250,000Total BMTs done ~ 3,000 ~ 300Risk group identification Good Poor

Transplant related mortality 5-40% 5-10%

Medical therapy Chelation effective but expensive

Hydroxyurea inexpensive but partially effective

Quality of life Potentially good Variable

Life expectancy Highly dependent on medical care

Potentially 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 transplantationConclusions 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