contents

table of
chairman?s 2 “The World Thalassaemia Family Heads for Dubai”

address
3 10th International Conference on Thalassaemia and
Haemoglobinopathies and 12th International TIF Conference for
recent events Thalassaemia Patients and Parents (contd on page 40)
“Your country has lost a noble leader, a respected politician and a
strong campaigner” TIF Chairman remembers the Sheikh Maktoum
bin Rashid Al Maktoum of the UAE
Events from Around the World

17 Thalassaemia after Dubai

Disturbances of Iron Homeostasis in Thalassaemias
medical focus New Approaches to Iron Chelation
Deferasirox: An update on new clinical studies on the oral chelator
Deferiprone versus desferrioxamine: Preliminary results of a
randomised clinical trial in patients with haemoglobinopathy
TIF Awards 2006

28 Forthcoming events

coming events 32 Prevention Book, Vol.2 - Order form

Other TIF publications
publications
34 News from Around the World

thalassaemia
worldwide

TIF Magazine
Thalassaemia International Federation P.O.Box 28807, 2083 Nicosia, Cyprus Tel: +357 22319129 / 22319134 Fax:+357 22314552 E-mail:thalassaemia@cytanet.com.cy
www.thalassaemia.org.cy
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Reproduction of material published in TIF Magazine for educational purposes is encouraged, provided it is accompanied by the following attribution: ”...according to TIF Magazine,
the official newsletter of the Thalassaemia International Federation”.

March 2006 / 1
 address
chair
man?s
-
D ear Friends,
Hope and courage are the driving
forces that help us all in the fight
against thalassaemia. And now,
more than ever, hope and courage
are in abundance.
The joint 10th International
Conference on Thalassaemia and
Haemoglobinopathies and 12th
International TIF Conference for
Thalassaemia Patients and Parents,
held in January 2006 in Dubai, was
a truly moving event.
Patients, parents, researchers and
medical practitioners came togeth-
er from across the globe to share
their experiences, their challenges
and, of course, their hopes. But
they also - perhaps unconsciously -
did much more than that. The
sheer will to fight demonstrated in
Dubai, particularly that of patients
and families, has formed a huge
reservoir of courage. Whether you
made it to the Conference or not,
that reservoir is there for us all to
draw on. I, for one, will draw freely
of it, as I hope you all will, too.
The search is now on for a host for
the next joint conference - the most
important event in the global tha-
lassaemia calendar - which is due
to be held in 2008. For more
details, visit the TIF website
(www.thalassaemia.org.cy).
Here at TIF, noses are back to the
grindstone, with a packed schedule
of events and projects for the forth-
coming months. From Delegation
Visits to field trips, workshops to
seminars, awareness campaigns to
new publications, TIF has a stream
of exciting events that aim to take
our work further than ever before,
promoting prevention and safe,
effective treatment in every corner
of the world.
2/ March 2006
The World Thalassaemia Family
heads for Dubai
By Panos Englezos, TIF Chairman
An important ongoing project is to
update TIF's Guidelines on the
Clinical Management of
Thalassaemia - a publication that
offers crucial guidance to practising
physicians, as well as helping
patients and families better under-
stand thalassaemia and its treat-
ment.
New publications currently being
prepared include Guidelines for the
Establishment and Functioning of a
National Thalassaemia Association,
The Use of Magnetic Resonance
Imaging (MRI) in the Management
of Thalassaemia and a Physician's
Personal Assistant - a problem-
solving guide for physicians
involved in the treatment of thalas-
saemia.
TIF also works hard to raise the
profile of thalassaemia within relat-
ed international organisations,
attending conferences and work-
shops around the world. Over the
coming months, TIF will be repre-
sented at the European School of
Transfusion Medicine's Residential
Course on Clinical Transfusion
Medicine (Liberec, Czech Republic,
29th March-2nd April 2006); the
3rd International Plasma
Fractionation Association Meeting
(Paris, France, 11th-12th April
2006); the International
Thalassaemia Summer School
(Antalya, Turkey, 23rd-27th April
2006); the 41st Annual Meeting of
the European Association for the
Study of the Liver (EASL) (Vienna,
Austria, 26th-30th April 2006); the
National Thalassaemia Workshop
(Kuala Lumpur, Malaysia, 3rd-7th
May 2006); the 13th Workshop of
the International Plasma
Fractionation Association (IPFA)
(Bern, Switzerland, 12th-13th June
2006); and the 29th Regional
Meeting of the International
Society for Blood Transfusion
(ISBT) (Capetown, South Africa,
2nd-7th September 2006).
And, of course, we will be busy
planning events to mark the 8th of
May - International Thalassaemia
Day - including attending the
National Workshop on
Thalassaemia due to be held in
Cairo, Egypt on the day itself. Look
out for the annual TIF 8th of May
poster, which promises to be as
colourful and informative as ever
and will be printed in nine lan-
guages.
Look out, too, for more details
about the forthcoming 10th
International Course on
Thalassaemia and Other Haemo-
globin Disorders, due to be hosted
in Nicosia, Cyprus in November
2006. (Keep an eye on our website,
www.thalassaemia.org.cy, for fur-
ther updates, as well as forthcom-
ing issues of TIF Magazine.)
Finally, I would like to extend a
warm welcome to TIF's new Board,
elected on the sidelines of the
Dubai Conference, along with our
heartfelt thanks to outgoing mem-
bers who have done so much to
support TIF in its work. Once
formed, bonds like this can never
be broken.
Readers, enjoy this packed issue of
TIF Magazine, and don't forget to
keep sending us your news and
views.
With best wishes for good health
and strong spirits.
Panos Englezos
TIF Chairman
 recent
events
10th International Conference on Thalassaemia
and Haemoglobinopathies and
12th International TIF Thalassaemia
Conference for Patients and Parents
7th-10th January 2006, Dubai, United Arab Emirates

T he 10th biannual International

Conference on Thalassaemia and
Haemoglobinopathies and parallel
12th International TIF Thalassaemia
Conference for Patients and
Parents, held at the Dubai World
Trade Centre in January 2006, were
amongst the most successful ever.
The two events are held simultane-
ously in order to facilitate the shar-
ing of information between key
stakeholders in the thalassaemia
world - patients, parents, medical
practitioners and scientists. And as
the record number of participants
showed, that is an approach that
works for everyone.
Almost 1,000 patients and 700
health professionals - including
representatives from the World
Health Organisation - attended
proceedings in Dubai, a cosmopol-
itan hub at the heart of the Middle
East.
As Conference participants soon
discovered, Dubai boasts a vibrant
culture and tradition of warm hos-
pitality, as well as some of the
world's best conference facilities.
There was also a focus on thera-
peutic options in thalassaemia, par-
ticularly gene therapy.
A major new addition
to the range of iron
chelators means Opening Ceremony.
much greater From left: Mr Al-Khayat, Mr Panos
flexibility in tailoring Englezos, Mr Loizos Pericleous, Mrs
Shobha Tuli.
treatment to
individual patients
On the subject of blood safety and
transfusion, conference delegates
heard expert opinion on significant
new findings on the use of appro-
priate iron chelators in relation to
transfusion-related iron overload. TIF General Meeting.
Presentations also addressed safety
issues, and outlined new technolo- There have also been significant
gies aimed at minimising the trans- advances on a number of other
mission of pathogens. fronts. First, considerable progress

10th International
Conference on Thalassaemia
and Haemoglobinopathies

Delegates to the 2006 International

Conference on Thalassaemia and
Haemoglo-binopathies gained criti-
cal insight into major develop-
ments in the field, including
endocrinology, liver disease, viral
hepatitis, thalassaemia intermedia,
sickle cell disease and the epidemi-
ology of thalassaemia, as well as
prevention, psychosocial aspects of
the haemoglobinopathies, and
patient survival and quality of life.
Social evening with the group from Malaysia.
Forward motion
On the subject of chelation thera-
py, delegates heard how a major
new addition to the range of iron
chelators currently available has
given medical professionals much
greater flexibility in tailoring treat-
ment to the needs of individual has been made in developing tech-
patients. niques for the measurement of iron

March 2006 / 3
load, with a number of new meth-
ods having been proved to accu-
rately measure levels of iron in the
heart and liver - some of which
have also received FDA approval.
It is no exaggeration
to say that the 12th
International TIF
Thalassaemia
Conference
surpassed all
expectations
Conference delegates also dis-
cussed developments in the man-
agement of cardiac, endocrine and
hepatic complications, which have
significantly improved the medical
care of patients with thalassaemia.
And there was extensive discussion
of advances in curative options for
thalassaemia, including presenta-
tions on the status of bone marrow
and cord blood transplantation.
Other options for the clinical man-
agement of thalassaemia discussed
included the use of drugs to modu-
late HbF, with new evidence pre-
sented on the use of existing prod-
ucts, as well as new drugs ready for
clinical trials.
Mr Panos Englezos, Mrs Shobha Tuli
and Mrs Fatemeh Hashemi, with the
group from Sri-Lanka.
Broadening the agenda
In addition to extensive coverage of
a great range of issues relating to
thalassaemia, this year's
Conference dedicated considerable
time and resources to other severe
haemoglobin disorders, particular-
4/ March 2006
ly HbE and sickle cell disease,
drawing on new epidemiological
data on their prevalence and
impact on public health.
Similarly, thalassaemia intermedia
was given special attention, with
the presentation of important new
data on complications in older
patients. It is expected that this
new data will provide valuable
insight in drawing up updated
guidelines on management of the
disease.
Genetic therapy around the
corner?
And last but certainly not least,
Conference participants were
informed of significant advance-
ments in the field of gene therapy,
with scientists from the United
States announcing their readiness
to commence clinical trials on
humans, for the first time - offering
the possibility, many hoped, of a
long-awaited breakthrough.
Dramatic advances in
the treatment of
thalassaemia are
imminent. But - as
patients know all too
well - the greatest
advances come
from within
The Dubai Conference featured
many noteworthy aspects. One
was a focus on issues such as
ethics, patients’ rights, informatics
(the storage of electronic data) and
the need for greater emphasis on
psychosocial care. Another was
the inclusion of interactive sessions
in which particularly interesting
clinical cases were presented as
‘food for thought’, further promot-
ing discussion amongst health pro-
fessionals.
Epidemiology and prevention -
twin supports in the control of tha-
lassaemia and other Hb disorders -
also received extensive attention,
with new data presented on
advances in technologies such as
PGD and maternal peripheral
blood diagnosis.
A key aim of the International
Thalassaemia Conference is to
encourage the spread of best prac-
tice - a goal that is sure to be boost-
ed by the participation of officials
from the WHO, which plays a key
role in advising national govern-
ments on the control and treatment
of thalassaemia.
12th International TIF
Thalassaemia Conference for
Patients and Parents
It is no exaggeration to say that the
12th International TIF Thalassaemia
Conference for Patients and
Parents surpassed all expectations.
The programme, drawn up by the
Board of TIF, was of an exception-
ally high standard. A particularly
popular feature of the programme
was interactive discussion focusing
on issues of interest and concern to
patients and parents. And the
record number of participants not
only came from the widest range of
countries, but from those most
highly affected by thalassaemia.
The overriding message from the
both the patient/parent and the sci-
entific Conferences was one of
hope, combined with an emphasis
on the power of the patient - that
is, the importance of complying
with treatment.
Patients were presented with evi-
dence of imminent, dramatic
advances in the treatment of tha-
lassaemia. But, participants heard,
the greatest advances come from
within - as patients know all too
well. Patients, with the support of
their families and medical practi-
tioners, must continue to seek the
determination to maintain them-
selves in as good a clinical condi-
tion as possible, helping their bod-
ies make the most of new thera-
peutic techniques.
There was good news, too, from
data on survival studies. Significant
advances in the clinical manage-
ment of thalassaemia, particularly
endocrine, cardiac and liver com-
plications, have improved patients'
quality of life as well as survival.
The message, in short, was that
thalassaemia is not only treatable,
it is a disease that can be managed
to ensure a high quality of life for
patients. See more photos p.40.
 “Your country has lost a noble leader,
a respected politician and a strong
campaigner”
TIF Chairman remembers the Sheikh Maktoum bin
Rashid Al Maktoum of the UAE
TIF Chairman
addresses
opening session
of Dubai
conference
T IF Chairman Panos Englezos
began his address to delegates by
extending his sincere condolences
to His Excellency Qadhi Saeed Al
Murooshid, Director-General of
the Department of Health and
Medical Services, on the death of
the Prime Minister of the United
Arab Emirates, His Highness
Sheikh Maktoum bin Rashid Al
Maktoum.
"Your country has lost a noble
leader, a respected politician and a
strong campaigner who has made
Dubai what it is and stands for
today. I speak on behalf of our tha-
lassaemia family when I say that
we share in your mourning and
respect for the loss of this great
man."
And he thanked the royal family
and the State of Dubai for proceed-
ing with the Conference during a
period of national mourning. He
also thanked Conference co-chair-
man Dr Abdullah Al Khayat, and
members of the Organising and
Scientific Committees for their sup-
port in bringing the Conference to
fruition.
Outlining the origins of the parallel
International Conference on
Thalassaemia and Haemoglo-
binopathies and International TIF
Thalassaemia Conference for
Patients and Parents, Mr Englezos
said a decision to hold a joint event
was taken in 1989, in a bid to facil-
itate the flow of information
between health professionals and
patients and parents on the clinical
management of thalassaemia.
What began as an annual pro-
gramme "has now developed into
an extensive and exciting biannual
programme covering all aspects of
thalassaemia and other haemoglo
binopathies, including but not lim-
ited to, updates on the latest
research, prevention and treatment
protocols," he said.
"For a long time, it has been TIF’s
hope to hold this event in the
Middle East - a region highly affect-
ed by thalassaemia and other
haemoglobin disorders, and one
that has struggled for years to over-
come the numerous and compli-
cated issues related to the preven-
tion and treatment of thalassaemia
and other severe haemoglobin dis-
orders. Memories of my first visit
to many countries in the region are
marked with the pain and despair
in the eyes of patients and parents
I met, and I cannot forget them.
"But with the passing of time, hope
and optimism have begun to
replace feelings of fear and uncer-
tainty for the future. The majority
of countries in the region can now
boast of success and achieve-
ments, and there is a confidence
and commitment to bring about
more improvements. The Board
and myself are not only happy, but
extremely proud to know that TIF
has contributed to this progress.
"TIF has been instrumental in
establishing national thalassaemia
associations around the world,
helping to give patients and parents
a strong voice to demand their
right to live well and to integrate
productively into society.
"Through its Educational Program-
me, TIF has worked with national
recent
events
associations to promote greater
awareness of thalassaemia
amongst the public and health pro-
fessionals alike, establishing a net-
work of collaboration throughout
the Middle East.
"And now our dream of holding an
International Conference on
Thalassaemia and Haemoglobi-
nopathies in the Middle East has
been realised. Our co-organisers
here in Dubai, the Government of
Dubai and the Department of
Health and Medical Services, have
worked extensively and diligently
to produce an exciting programme
for all participants.
"The careful attention paid to the
choice of Conference venue has
paid off: as you will see for your-
selves, the Dubai World Trade
Centre offers comfort and diverse
facilities, providing everything
required for a productive
Conference.
"At the same time, the TIF
Organising Committee has worked
hard to design a new format for the
Patients and Parents Conference.
Participants will receive thorough
updates on research and treatment,
with plenty of opportunity to par-
ticipate in the Scientific
Programme, particularly in ses-
sions addressing new advances in
clinical management and therapeu-
tic options.
"In an important new development,
the programme also includes a
forum for patients and parents to
interact amongst themselves, facili-
tating the exchange of ideas,
knowledge and experience. And
this year's Conference will include
patient speakers from five regions
of the world, who will address the
patient-audience on their experi-
ence of ‘Living with Thalassaemia’
in their country."
March 2006 / 5
Thanking the TIF Board of
Directors, Mr Englezos concluded
by once again extending his grati-
tude to the Government of Dubai,
and to His Excellency Qadhi Saeed
Al Murooshid.
He also thanked the members of
the Organising Committee, in par-
ticular Conference co-chairman Dr
Abdullah Al Khayat, Abdullah Bin
Souquat, Abdul Salam Al Madani
and Abdulbasit Merdas of the
Emirates Thalassaemia Society, as
well as the Secretariat, headed by
Attracta di Silva.
Finally, he extended special thanks
to Scientific Advisers Professor Ali
Taher, Dr Michael Angastiniotis
and Dr Androulla Eleftheriou, and
to Judy Kalotheou of TIF, "for taking
this Conference to heart and for
providing essential support to the
organisers in Dubai".
Dubai, UAE,
January 2006
TIF Meetings
with Country
Delegations
T he wide range of participants at
the International Thalassaemia
Conferences in Dubai offered an
excellent opportunity for smaller
meetings between members of the
TIF Board and representatives of
various national thalassaemia asso-
ciations, including patients, parents
and health professionals.
These sessions enabled individual
country representatives to discuss
particular concerns with members
of the TIF Board, prompting in-
depth discussions on issues relat-
ing to the prevention or clinical
management of thalassaemia in
their country, as well as problems
faced by patients, parents and
health professionals.
Amongst the meetings held in
Dubai, TIF Chairman Panos
Englezos, TIF President Shobha Tuli
and TIF Board Members Fatemeh
Hashemi and Bob Ficarra met rep-
resentatives from Albania (led by
Deputy Health Minister Aleksander
Sallanbanda), Bangladesh, Sri
6/ March 2006
Above photos are from TIF’s meeting
with the Delegation group from Turkey.
Group photo of participants from
Albania.
From left: Dr Aleksander Sallabanda,
(Deputy Minister of Health, Albania),
Dr Michael Angastiniotis (TIF, Cyprus)
and Mr Muca Zenelaj (Albania National
Thalassaemia Association).
Lanka, Nepal, Iraq and Turkey.
Over the past two years, TIF has
made particular efforts to support
work in Albania, whilst a TIF
Delegation Visit to Sri Lanka in
December 2005 marked the con-
tinuation of TIF’s active support of
efforts there.
Meeting with Conference delegates
from Turkey, delegation leader
Professor Canatan of the
Thalassaemia Federation of Turkey
and Professor Yesim Aydinok out-
lined recent progress in the control
of thalassaemia in the country.
Meanwhile, representatives from
Bangladesh, Nepal and Iraq
requested TIF’s further support for
local patients, parents and health
professionals. These three country
associations will shortly be submit-
ting written reports to TIF, outlin-
ing the challenges faced, helping
TIF to identify the ways in which it
can help, including a detailed Plan
of Action.
TIF satellite
meetings in Dubai
I n addition to meeting with coun
try delegates, the Dubai Confe-
rence provided an excellent oppor-
tunity for TIF Board Members to
hold fringe meetings with key
organisations and individuals active
in the fight against thalassaemia,
including:
ñ Dr Victor Boulyjenkov, head of
WHO's department of Non-
Communicable Diseases, during
which the WHO/TIF 3-year joint plan
of activities was discussed in detail
ñ Members of the Asian Network
Group, including Professors Suthat
Fuchareon and David Weatherall and
Drs Ratna Chatterjee and Farruk
Shah. Discussion focused on pro-
moting further collaboration with
the Asian Network and expanding
future activities, including develop-
ing academic training courses on
thalassaemia
ñ Professor Susan Perrine and Dr
Michele Sadelein, who updated TIF
Board Members on progress in cura-
tive techniques for thalassaemia,
including gene therapy and the
pharmaceutical induction of HbF.

Events from Around the World
Dubai, UAE,
7th January 2006
TIF General
Meeting
T
he 2006 General Meeting of the
Thalassaemia International
Federation (TIF), held every two
years during the course of the bian-
nual International Conference on
Thalassaemia, took place on 7th
January in Dubai.
All Federation members are
encouraged to take part in what is
one of the most important TIF
events - not least this year's, during
which a new TIF Board was elect-
ed. A new Board is elected every
four years.
More than 350 members from 45
countries gathered for the 2006
meeting. TIF Chairman Panos
Englezos presented a detailed
report on Federation activities
since the last General Meeting,
held in Palermo, Sicily on 16th
October 2003. Members were also
provided with an overview of
future plans, and reviewed and
approved Minutes of the last
General Meeting, accounts for
2004/2005 and the budget for
2006.
Members also agreed that a deci-
sion on where to hold the next
International Conference would be
decided by the new Board of
Directors at its next official meet-
ing.
TIF Voting Members then elected
by secret ballot a new Board of
Directors, consisting of seven
patients and seven non-patients.
Newly-appointed Directors met
immediately after the General
Meeting, to elect officers to posi-
tions on the Board.
The new TIF Board of Directors
Panos Englezos (Cyprus) Chairman
Shobha Tuli (India) President
Michael Michael (UK) 1st Vice
President
Dawn Adler (USA) 2nd Vice President
Riyad Elbard (Canada) Treasurer
Katrina Demetriou (UK) Assistant
Treasurer
Anton Iskafi (Palestine) Assistant
Secretary
George Constantinou (UK) Board
Member
Robert Ficarra (USA) Board Member
Mouna Haraoui (Lebanon) Board
Member
Fatemeh Hashemi (Iran) Board
Member
Mohammed Imran (Pakistan) Board
Member
Christina Stephanidou (Greece)
Board Member
Ramli Mohd Yunus (Malaysia) Board
Member
TIF wishes to thank members of
the new Board for their commit-
ment to the work of the Federation,
and for the sacrifices they will
make in supporting TIF members
and staff.
Dubai, UAE,
6th January 2006
Outgoing TIF
Board holds
final meeting
M embers of the outgoing Board
of Directors held their last meeting
recent
events
on 6th January 2006 in Dubai, a
day ahead of the TIF General
Meeting at which a new Board was
elected. Items for discussion were
limited to general business and the
following day's General Meeting.
Members of the TIF Board
of Directors, 2002-2006
Panos Englezos Chairman
Shobha Tuli President
Martina Fanari Vice President
Costas Anastasiou Secretary
Dawn Adler Assistant Secretary
Riyad Elbard Treasurer
Merulla Steagal Assistant Treasurer
Robert Ficarra Past President
George Constantinou Board Member
Katrina Demetriou Board Member
Mouna Haraoui Board Member
Fatemeh Hashemi Board Member
Yousef Nawwab Board Member
Odysseus Platis Board Member
TIF wishes to thank members of
the outgoing Board for their dedi-
cation and hard work, and looks
forward to continuing to work
together in the fight against thalas-
saemia.
Istanbul, Turkey
30th September 2005
4th Middle East
Thalassaemia
Investigators
and Thought
Leaders meeting
T he Middle East Thalassaemia
Investigators and Thought Leaders
Group, a unique organisation
March 2006 / 7
working to promote better commu-
nication of developments in the
field of thalassaemia, held its fourth
annual meeting on 30th September
2005 in Istanbul, Turkey.
The 2005 scientific forum was
divided into two parts. The first
focused on new developments in
iron chelation and the largest ever
prospective clinical trial for such a
drug, while the second provided an
opportunity for delegates to hear
from regional experts on iron
chelation, who shared their expert-
ise and research findings.
The Middle East Thalassaemia
Investigators and Thought Leaders
Group brings together leading
Middle East researchers, practition-
ers and activists in the field of tha-
lassaemia and other hereditary
anaemias. A primary function of
the Group is to communicate cut-
ting-edge research to a wider audi-
ence. However, the organisation
also seeks to raise public aware-
ness about thalassaemia, including
alerting patients and parents to the
importance of proper diagnosis
and treatment of the disease, and
of prevention - areas in which it
works closely with the
Thalassaemia International
Federation (TIF).
Source: Professor Ali Taher, American
University of Beirut
TIF Delegation
visits, 2005
T he fight against any disease - not
least thalassaemia - depends not
just on expert knowledge and
resources, but on high quality data.
Without an understanding of the
spread and prevalence of a disease,
it is impossible to know what level
of assistance is required, and
where.
As part of its work to assist coun-
tries seeking to improve the treat-
ment and prevention of thalas-
saemia, TIF has therefore placed
considerable emphasis on the col-
lation of good data on the spread
and prevalence of the disease. In
8/ March 2006
some regions, such as Eastern
Europe, such data has been partic-
ularly lacking - and so a TIF
Delegation visit to Bulgaria in
November 2005 was a great oppor-
tunity to boost co-operation with
thalassaemia organisations work-
ing in the country, with the aim of
filling the gap.
Other recent Delegation visits were
just as productive. A visit to Sri
Lanka offered TIF its first on-the-
ground view of thalassaemia in the
South Asian island nation, while a
visit to Germany provided insight
into thalassaemia in a highly-devel-
oped European state - including
surprising similarities in the chal-
lenges faced. (In Germany, too,
data collection has proved an area
in need of additional attention,
while psychosocial issues, securing
sufficient funding and attracting
medical practitioners to the field
are as much an issue as they are
anywhere else.)
TIF Delegation visit to Bulgaria
19th-22nd November 2005
The four-day TIF Delegation visit to
Bulgaria was attended by Panos
Englezos (TIF Chairman),
Constantinos Anastasiou (TIF
Board Secretary), Elias Sofianos
(TIF Board Member), Anelia
Todorova (Member of the
Bulgarian Anti-Thalassaemia
Organisation) and Dr Androulla
Eleftheriou (TIF Scientific Director).
The group was accompanied by
Stefka Klaeva (President of the
Bulgarian Anti-Thalassaemia
Association) and Nikola Vouchkov
(Novartis Oncology Representative
in Bulgaria) both of whom provided
great support throughout the trip.
TIF has longstanding links to the
thalassaemia community in
Bulgaria, bolstered by the regular
attendance of Bulgarian medical
specialists on TIF educational pro-
grammes, including International
Courses on the Clinical
Management of Thalassaemia.
However, the lack of a national
patient/parents' association was
felt to be a particular hindrance to
further strengthening TIF activities
in the country - until last year's
establishment of the first such
national association in Bulgaria, set
up with TIF support. Indeed, the
decision to organise a Delegation
visit to Bulgaria was in no small
part due to association requests for
TIF to intensify its work to help
implement changes in prevention
and clinical management policies
in the country.
Meeting with patients, parents,
physicians and the media
Radissons Hotel, Sofia
20th November 2005
Official Delegation activities kicked
off with a meeting of 150 patients
and parents, joined by 45 specialist
physicians from all over Bulgaria -
an event that also received exten-
sive coverage in the local media.
The meeting heard that about 300
thalassaemia major patients are
registered in Bulgaria. However,
there were calls for a national
patient register to be established,
to facilitate better financial plan-
ning in the delivery of treatment.
There were calls, too, for a
strengthening of national policies
aimed at the prevention and clini-
cal management of thalassaemia,
including public awareness cam-
paigns, and for a special education-
al programme for thalassaemia
patients and parents.
A strong media presence at the
meeting helped ensure the widest
possible dissemination of proceed-
ings, including information gleaned
from the official TIF DVD on tha-
lassaemia, screened to a packed
conference room.
The meeting was also an opportu-
nity for members of the TIF
Delegation to discuss the chal-
lenges facing thalassaemia patients
and parents in Bulgaria, as well as
those facing treating physicians.
TIF Delegation group meeting with the
Deputy Minister of Health of Bulgaria
Dr Matey Mateev.

Proceedings were translated into
Bulgarian by Ms Todorova and Mr
Vouchkov, greatly facilitating TIF
Delegates' interaction with patients
and parents.
Over 70% of
thalassaemia patients
in Bulgaria receive
blood transfusions &
iron chelation therapy
- a significant increase
on previous figures
Visit to St George's Hospital,
Plovdiv and the General
Hospital, Stara Zagora
21st November 2005
The following day, the TIF
Delegation was taken outside Sofia,
to visit two provincial treatment
centres, in Plovdiv and Stara
Zagora.
During both visits, Delegation
members met with patients and
their parents, learning more about
the challenges faced by thalas-
saemia patients and their families
in Bulgaria.
At St George's Hospital in Plovdiv,
the group was escorted around the
thalassaemia centre by Dr
Stoyanova.
At the Stara Zagora General
Hospital, the Delegation was host-
ed by Assistant Professor
Chakarova.
Visit to two chemotransfusion
departments, Sofia
22nd November 2005
On the morning of 22nd
November, the TIF Delegation paid
a visit to two chemotransfusion
departments, both in Sofia.
Escorting the group was Associate
Professor Andreev, Head of the
National Blood Bank Centre, Dr
Mirella Rangalova and Dr
Stoyanova.
Meeting with Bulgaria's Deputy
Minister of Health
22nd November 2005
In the afternoon of 22nd
November, the TIF Delegation was
very fortunate to have a meeting
with Bulgaria's Deputy Minister of
Health, Dr Matei Mattev.
The meeting was extremely pro-
ductive, with discussions focusing
on TIF recommendations for fur-
ther strengthening policies aimed
at the prevention and clinical man-
agement of thalassaemia in
Bulgaria.
At the same time, TIF representa-
tives were keen to emphasise the
considerable progress already
made in improving the treatment
offered to thalassaemia patients in
Bulgaria. Over 70% of patients now
receive blood transfusions and iron
chelation therapy - a significant
increase on previous figures.
Given the solid advances made so
far, Delegation members reiterated
TIF's commitment to supporting
efforts by the national health
authorities to see still further
improvements.
The meeting ended with a commit-
ment for TIF and Bulgaria's
Ministry of Health to work togeth-
er in support of Ministry efforts to
implement improved protocols on
the prevention and clinical man-
agement of thalassaemia, promote
public awareness of the disease,
and address related issues such as
blood safety and adequacy.
Dr Mirella Rangelova and Dr Androulla
Eleftheriou chat with a patient
Delegation members also drew
attention to the newly-founded
Bulgarian Anti-Thalassaemia
Association, whose members now
number over 110. TIF strongly
believes that, like all national
patient/parent groups, Bulgaria's
first such organisation will greatly
facilitate better collaboration
between TIF and Bulgaria's medical
community and national health
authorities, in the interests of
improving the treatment and pre-
vention of thalassaemia in the
country.
Plan of Action
Following its Delegation visit to
Bulgaria, TIF has drawn up an
action plan for activities in the
country:
1. Organisation of an educational
National Thalassaemia
Workshop in collaboration with
the Bulgarian Anti-Thalassaemia
Organisation, the Bulgarian
medical community and nation-
al health authorities, aimed at
(i) health professionals,
(ii) patients and parents and
(iii) the public.
Proposed date: September 2006
2. Participation of medical special-
ists from across Bulgaria in the
10th Educational Course on
Thalassaemias and Other
Severe Haemoglobin Disorders.
November 2006, Nicosia,
Cyprus
3. Formulation of a proposal for
i) guidelines on the treatment
of thalassaemia and its compli
cations in Bulgaria, and
ii) policies for the effective
prevention of thalassaemia in
Bulgaria.
4. Promotion of increased collabo-
ration between Bulgarian asso-
ciations and international
health organisations, including
the World Health Organisation
(WHO), the International
Society for Blood Transfusion
(ISBT), the Red Cross and the
European School of Transfusion
Medicine (ESTM), in order to
raise public awareness of the
importance of voluntary non-
remunerated regular blood
donation.
5. Translation of TIF publications
into Bulgarian.
March 2006 / 9
Symposium on Current
Issues in Iron Overload
in Rare Anaemias
University Medical
Centre Hamburg-
Eppendorf, Germany
13th-16th October 2005
TIF Delegation
visit to Germany
2005
A TIF Delegation visit to
Germany in October 2005 was
timed to coincide with the interna-
tional Symposium on Current
Issues in Iron Overload in Rare
Anaemias, held at the University
Medical Centre in Hamburg-
Eppendorf.
Thalassaemia in Germany
Germany is one of the world's
leading economies and boasts a
highly developed healthcare sys-
tem. Nonetheless, thalassaemia
patients face challenges in securing
the resources they need, particular-
ly in terms of numbers of medical
specialists.
Thalassaemia carriers amount to
around 0.3% of Germany's total
population of 82.5 million. All car-
riers come from ethnic minority
groups - a fact that contributes to
the low level of awareness about
thalassaemia, its treatment and
prevention.
The majority of patients with tha-
lassaemia major in Germany are
transfusion dependent. However,
there are only a few specialist cen-
tres in the country, such as Ulm
and Hamburg. Given their geo-
graphical spread, it is very rare for
any one centre to treat more than
20-30 patients annually. Many
patients receive treatment in even
smaller numbers in general clinics
or hospitals.
As in many other European coun-
tries, the fact that patients suffering
from thalassaemias and other
severe haemoglobinopathies are
from ethnic minorities spread
across the country makes it difficult
10 / March 2006
to generate interest and awareness
about the disease - amongst the
medical profession, policy-makers
and the public alike. However,
increased effort to strengthen
patient/parent groups should help
empower affected communities to
lobby for improved services.
According to a paper by Cario,
Stahnke and Kohne (2000), there
are at about 300-400 patients with
thalassaemia major living in
Germany. The study abstract (see
below) gives a brief overview of the
state of care available in Germany.
A multi-centre study begun in 1991
has identified all patients suffering
from thalassaemia, as well as
establishing a uniform therapy pro-
tocol and follow-up diagnostic pro-
cedures.
After six years of study, data on
198 thalassaemia major patients
were analysed. The majority of
patients were found to originate
from endemic regions around the
Mediterranean Sea. During the
period of observation, a decreasing
number of patients aged 15 to 21
presented with ferritin levels above
2500 ng/ml. However, amongst
treated patients aged 9 to 15, more
than half presented with complica-
tions such as cardiac disease
(13%), liver disease (21%),
impaired glucose metabolism
(14%), hypothyroidism (24%) and
hypogonadism (59%). These values
did not change considerably during
the period of observation, apart
from an increase in cardiac disor-
ders to 20%. Thus in Germany, as
in many other countries, a lack of
compliance with treatment is par-
ticularly problematic in adolescent
patients, requiring greater focus on
this age group.
In terms of epidemiology, two arti-
cles provide a general background
on the genetic make up of the
forms of thalassaemia most preva-
lent in Germany. Schwarz, Vetter,
Kohne and Kulozik (1997) investi-
gated "the 300-400 patients with
homozygous b-thalassaemia cur-
rently in Germany, who migrated
from endemic regions mostly in the
Mediterranean. In the non-immi-
grant population b-thalassaemia is
rare with only single case reports of
homozygous patients.
Heterozygous ‚-thalassaemia,
however, is more common and
must be considered in the differen-
tial diagnosis of hypochromic
anaemia."
The clinical and molecular data of
221 homozygous patients from
immigrant families and 256 non-
immigrant German heterozygous
individuals are presented.
Clinically, 87% (n = 192) of the
homozygotes are regularly trans-
fused and classified as thalas-
saemia major (TM). The other 13%
(n = 29) are not (regularly) trans-
fused and thus classified as thalas-
saemia intermedia (TI). There is a
wide spectrum of 39 b-globin gene
mutations and even the most com-
mon three, IVSI-110G-A, NS 39
and IVSI-6 T-C, occur with relative-
ly low frequencies of 28%, 22% and
9%, respectively. In 17/29 (58%) TI
patients "mild" mutations are found
that inactivate the affected gene
incompletely. In 16/29 (55%) there
are mutations that are associated
with increased gamma-globin gene
activity. a-thalassaemia is rare and
only found in 3/29 TI-patients.
In the 256 Germans with heterozy-
gous ‚-thalassaemia there are 27
different ‚-globin gene mutations.
The three most common are
Mediterranean mutations, which
together account for 61% of the
affected population. Also relatively
common (5%; n = 13) is an other-
wise rare frameshift mutation of
codon 83 (FS83 delta G). The other
mutations occur in less than 10
individuals.
Two mutations described here are
novel. One of them affects posi-
tion-2 of the intron 1 splice accep-
tor site (IVSI-129 A-G) and the
other is a deletion of a single G in
codon 15/16 (FS 15/16 delta G)."
In the work of Flatz, Wilke,
Syagailo, Eigel and Horst (1999),
"the ‚-thalassaemia mutations of
13 unrelated heterozygous
Germans who remained unidenti-
fied in a previous study of 40 sub-
jects were investigated at the DNA
level. Two Mediterranean, one
Asian and three novel mutations
(CD6 -G, CDs 108 /112-12nt, CDs
130/131 + GCCT) were identified.
Altogether, in 30 of the 35 subjects
(86%) in which a mutation in the b-
globin gene was identified, the
mutation was of Mediterranean ori-
gin. The geographical distribution
suggests recent migration from the
Mediterranean region as cause of
the high proportion of frequent
Mediterranean ‚-thalassaemia
mutations in the German popula-
tion. The results support the notion
that the majority of ‚-thalassaemia
genes in the western and central
European population are of
Mediterranean origin."
In terms of counselling, the work of
Schwarz, Vetter, Kohne and
Kulozik (1997) (see box) indicates
that "taken together, a plausible
molecular pathogenesis for the
observed phenotype (TM vs. TI)
can be identified in most homozy-
gous patients, thus allowing for
rational counselling of the affected
families. In heterozygous Germans
‚-thalassaemia has probably been
imported from the Mediterranean
in about two-thirds of cases,
whereas in the remaining one-third
it has probably originated locally."
It's all about compliance...
Interesting work has also been
done investigating the psychosocial
problems faced by thalassaemia
patients in Germany, with the
demands of treatment often found
to be the root of more problems
than the condition itself.
Two studies have investigated
patient coping strategies. The first,
by Goldbeck, Baving and Kohne
(2000), indicated that the long-
term outcome in thalassaemia
depends on patient ability to
adhere to treatment protocols
aimed at reducing iron loading.
The study correlated self-reported
adherence to iron chelation treat-
ment with age, gender, age at the
start-point of treatment and emo-
tional distress, finding that:
"Complaints, coping strategies and
locus of control are independent
from adherence as well as from
haemosiderosis."
Patients were found to react to dis-
ease-related distress with a variety
of coping strategies. According to
the authors, some of the most fre-
quently adopted strategies proved
to be maladaptive, indicating feel-
ings of helplessness. Describing
coping strategies from a patient
perspective, including "health-relat-
ed locus-of-control-beliefs and psy-
chosocial influences on adher-
ence", the study found that clinical
symptoms of iron loading were
correlated with psychosocial vari-
ables, with patients feeling more
distressed by aspects of treatment
than the illness itself.
...and support
According to the study, "Internal
locus-of-control-beliefs were low
while fatalistic locus-of-control-
beliefs were high compared with
other clinical groups." The authors
concluded: "Patients with thalas-
saemia major need more informa-
tion about their disease and about
the benefits of iron chelation thera-
py. Additional psychosocial sup-
port should reduce emotional dis-
tress, strengthen coping compe-
tence and lead to a better integra-
tion of therapy in daily life."
A second study, by Hoch, Gobel
and Janssen (2000), found that "the
prognosis and therewith the quality
of life of patients with ‚-thalas-
Thalassaemia in Germany
Total number of carriers :
(except ·+)
Total number of carriers as % of population :
‚-thalassaemia major trait-carriers :
·o-thalassaemia trait as % of population :
Total ‚-thalassaemia patients as % of carrier population:
Total transfusion-dependent ‚-thalassaemia patients :
(est.)
No. of carrier births per year :
No. of ‚-thalassaemia carrier births per year :
Total homozygote birth rate per year per thousand:
Source: Modell 2004 Epidemiological Data
saemia major is decisively influ-
enced by the compliance with the
therapy of the patients and their
families, who are massively bur-
dened with this lifelong and time-
consuming treatment."
In an effort to improve levels of
compliance amongst young peo-
ple, an association of patients aged
between 15 and 27 was founded in
1992. With ten initial members, the
organisation aimed to establish the
reasons for low levels of compli-
ance, and to promote an exchange
of experiences and provide com-
prehensive information on medical
aspects of the disease - all in the
hope of improving patients' sense
of responsibility for - and actual -
compliance with treatment.
Group members meet in monthly
sessions, to discuss topics such as
the interaction between parents
and children with a hereditary dis-
ease, issues surrounding self-image
and body image, and perceived
possibilities and limits to the inte-
gration of chronically ill patients in
educational and professional envi-
ronments. The authors conclude
that: "Although two members of
this group have died, our patients
show more interest in their dis-
ease, their therapy and their
prospects since the beginning of
this psychosocial care." Most
importantly, the authors note that
compliance has improved in the
majority of patients.
230,000
0.28 %
154,700
0.01%
67.38%
450-600
3,180
1,780
0.11
March 2006 / 11

Over recent years, the German thalassaemia register has not been ade-
quately maintained. Data presented in the following table, indicating the
number of patients treated in centres around Germany, is therefore
based on historical data, projected forward.
STATE CITY
Baden-Württemberg Ulm
Hamburg Hamburg
North Rhine-Westphalia Düsseldorf
Baden-Württemberg Stuttgart
Lower Saxony Göttingen
Berlin Berlin
Other
Source : Historical Register data via H. Cario
14th-16th October 2005
Symposium on
Current Issues
in Iron Overload
in Rare
Anaemias
T he two-day Symposium on
Current Issues in Iron Overload in
Rare Anaemias, held at the
University Medical Centre
Hamburg (UKE) at Eppendorf,
aimed to update the haematologi-
cal community on recent advances
in the field. Speakers included
national as well as international
experts, drawn from as far afield as
California and Israel.
Germany has a comparatively small
number of haematological centres
with specialised knowledge of rare
anaemias, and many patients are
treated in more mainstream hospi-
tals. The Symposium therefore also
served as a valuable platform for
patients and parents to meet each
other as well as experts in the field,
with special sessions focusing on
psychosocial issues and a round-
table discussion on better ways to
respond to the expectations of
patients and parents. There was
also an opportunity for patients and
parents to view a demonstration of
UKE's SQUID scanner.
TOTAL PATIENTS
20-30
20
10-15
10
20-30 (est.)
Unknown
5-10 (est.)
Day 1
Scientific presentations focused on
iron overload in a number of rare
anaemias. Those relating to thalas-
saemia included:
Professor Roland Fischer, UKE,
Germany, on Non-invasive Iron
Measurements with SQUID and
MRI
An overview of methods used to
assess total liver iron using SQUID.
Additional comparisons of the use
of SQUID in measuring significant-
ly lower iron concentrations in the
heart and myocardium. Also pro-
vided a review of recent develop-
ments in measuring iron levels in
the liver and heart, and empha-
sised the need to establish accurate
tools measuring the effects of iron
on other organs.
Dr Holger Cario, University
Children’s Hospital, Ulm,
Germany, on Haemosiderosis-
related Complication in Patients
with Thalassaemia Major
An overview of the problems and
complications arising from inade-
quate iron elimination therapy fol-
lowing chronic transfusion.
Explained the mechanism of com-
plications in the main organs and
the importance of early diagnosis
and appropriate treatment.
Dr Antonis Kattammis, Aghia
Sophia Children’s Hospital, Athens,
on Iron Load in Patients with
Thalassaemia
A discussion of why non-trans-
fused patients with thalassaemia
intermedia (TI) suffer iron over-
load. Using data from 37 non-
transfused patients with TI, demon-
strated that elevated ferritin levels
were related to elevated NTBI plas-
ma levels, and to the degree of ery-
thropoietic activity. Also pointed to
possible mutations in iron-regulat-
ing proteins that may further nega-
tively affect iron homeostasis in TI
patients.
Professor Paul Harmatz, Children’s
Hospital and Research Centre,
Oakland, CA, USA, on Advances in
the Treatment of Hepatitis C Virus
Infection in Thalassaemia
Considered results of a study of
HCV-infected thalassaemia major
patients and their treatment with
combination peginterferon alfa
(PegIFN) and ribavirin (RBV), chart-
ing their progress and sustained
viral response rates (SVRs).
Although the sample was small
(n=6), the study found a 50-55%
SVR, indicating that patients with
thalassaemia can demonstrate a
sustained viral response similar to
the general HCV-infected popula-
tion, without significant complica-
tions.
Dr Peter Nielsen, UKE, on
Diagnostic Use of SQUID in
Patients with Haemosiderosis and
Haemochromatosis
Explained the clinical benefits of
monitoring iron stores in the liver
(LIC) using SQUID-biosusceptom-
etry rather than the less direct
parameter of serum ferritin.
Demonstrated that the former
technique is a reliable and precise
parameter for monitoring iron
chelation therapy and a reliable and
cost-effective diagnostic tool, par-
ticularly in young patients.
Day 2
Further interesting insights were
delivered on Day 2 of the
Symposium, including the follow-
ing of particular interest to those
involved in thalassaemia:
Professor Piga, Department of
Paediatric Haematology/Oncology,
Torino, on State-of-the-art-manage-

12 / March 2006
ment of Haemosiderosis in
Thalassaemia.
An overview of various techniques
for removing excess iron accumu-
lated as a result of regular transfu-
sions, including sub-cutaneous
slow DFO infusion, continuous
intravenous DFO infusion, sub-
cutaneous bolus DFO administra-
tion, according to compliance
rates. Also reviewed the efficacy of
new oral chelators - DFP/L1,
ICL670 and GT56 - administered
separately or in combination, and
considered evidence of synergis-
tic/additive effects of combining
chelator type and method of
delivery.
Dr Regine Grosse, UKE, on Bone
Density Measurements in Patients
with Iron Overload.
Presentation of results of bone
density measurements using DXA
scans, in a group of patients aged
8-32. Included discussion of cur-
rent thinking on the pathogenesis
of low BMD in thalassaemia major
and intermedia, its relation to
endocrine dysfunction and cortical
bone diminution due to bone mar-
row expansion, and to chelator tox-
icity. Concluded with a call for DXA
scanning to be initiated from the
age of 10, and for supplementary
treatment where bone density
decreases.
Dr Mark Tanner, Royal Brompton
Hospital, London, on Baseline
Findings of a CMR-driven
Randomised Controlled Trial of
Iron Chelation Therapy in
Thalassaemia Major.
Presentation of baseline results
from a study of thalassaemia major
patients in Cagliari, treated with
DFX/placebo and DFX/DFP combi-
nation, indicating that myocardial
siderosis - present in two-thirds of
patients on DFX maintenance
doses - was related to a high preva-
lence of impaired LVEF serum fer-
ritin but not to liver iron. The find-
ings provide the first randomised,
placebo-controlled evidence that
myocardial iron is more effectively
reduced using combination therapy.
Dr Fernando Tricta, ApoPharma
Inc., on the Role of Deferiprone in
Reducing Morbidity and
Mortality in Iron Overload.
Highlighting the particular charac-
teristics of Deferiprone - along with
relevant explanatory studies - that
may explain the mechanisms and
specific physiochemical character-
istics that make Deferiprone more
efficient in removing iron from the
myocardial cells, thus reducing
morbidity and mortality in thalas-
saemia major and intermedia
patients.
Dr Danielle Alberti, Novartis, Basel,
on Defarasirox: Recent results from
the global clinical trials programme
An overview of latest results from a
global trials programme for
Novartis’s new once-daily oral
chelator, demonstrating that at 20-
30mg/kg, Defarasirox is as effective
as DFX in controlling body iron
burden, with acceptable safe-
ty/tolerability profiles. Reported
adverse effects included nausea,
vomiting, abdominal pain, diar-
rhoea, constipation, skin rash and
mild increases in serum creatinine.
Professor Pia Massaglia, Paediatric
Department, University of Turin,
on Specific Aspects of
Psychological Care in Thalassaemia
and Other Rare Diseases
An assessment of the constant evo-
lution in psychological needs of
adult patients, arising from physical
status and treatments, and requir-
ing a periodic redefinition of the
balance of risks and possibilities.
Described how this is achieved in
the Turin thalassaemia centre, and
it requires of patients, parents,
partners and hospital and medical
staff from a patient's early child-
hood through adult life.
Roundtable Discussion: The expec-
tations of parents and patients with
haemoglobinopathies from medical
caretakers and researchers
Format: Patients ask, doctors
answer
A very informative open session, in
which patients, parents and associ-
ation representatives described to
doctors experiences, expectations
and disappointments in the course
of receiving treatment for thalas-
saemia in Germany, including feel-
ings of despair and isolation.
Included a debate on ways to
improve services offered to thalas-
saemia patients and families.
Chaim Hershko, Shaare Zedek
Medical Centre and Hebrew
University, Jerusalem, Israel, on
Aims of Iron Chelation Therapy
A quick overview of current med-
ical knowledge about available
chelators, together with compli-
ance issues faced by patients. Also
outlined were reasons for increas-
ing the availability of alternative,
oral chelators, their pros and cons,
and the optimal combination of
available chelators.
Roundtable discussion on
Recommendations for Iron
Chelation Therapy
Format: Doctors ask, doctors
answer
An open-ended Q&A session on
the following issues:
1. Actual/optimal chelation therapy
in standard patients with thalas-
saemia major, intermedia and
minor, Blackfan Diamond, sickle
cell, MDS and haemosiderosis
post-bone marrow transplant
2. Patients with complications (e.g.
cardiac, hepatic, endocrinologi-
cal)
3. Combination of different chela-
tors (additive or synergistic
effects)
4. Iron overload diagnostic tools
(blood results, ferritin, liver
biopsy, non-invasive LIC, MRI,
SQUID R2* and T2*)
5. Intense iron chelation therapy,
role of high dose intravenous
DFX
6. Iron chelation and pregnancy
TIF Delegation Visit
The TIF Delegation was fortunate
to attend the Symposium on rare
anaemias, which was an extremely
well-organised and informative
event, offering great insight into
developments in thalassaemia in
general, as well as the status of the
disease in Germany. UKE is to be
congratulated on its achievement
in hosting the event.
March 2006 / 13
The Delegation was also struck by
the work of Hamburg patient
leader Katerina Nassis-Klaus and
the Ulm Parents Thalassaemia
Society. Their dedication and ener-
gy in promoting the welfare of tha-
lassaemia patients in Germany is
inspiring.
Clinical symptoms
of iron loading are
correlated with
psychosocial
variables, with
patients feeling
more distressed by
treatment than the
illness itself
A key issue in the treatment of tha-
lassaemia in Germany, clearly high-
lighted during the TIF Delegation's
visit to the country, is the highly
dispersed patient population - a
fact referred to by everyone from
patients to parents to medical staff.
This dispersal has made it particu-
larly difficult for the local associa-
tion to reach out to patients and
their families. Unofficial estimates
(see table, above) indicate that
about 20-30 patients are treated in
Ulm, 20-30 in Göttingen, 20 in
Hamburg, 10-15 in Düsseldorf
and10 in Stuttgart. A number of
other hospitals treat around 5-10
patients each.
One way forward may be to co-
operate with an EU-funded pro-
gramme aimed at establishing a
European Network for Rare and
Congenital Anaemias (ENERCA-I),
which started in September 2005
and comprises a number of
European centres, including
Germany's Klinikum der
Universität Ulm.
The programme has a number of
aims, including maintaining a
patient register; assessing the qual-
ity of patient care; providing early
warning of clinical problems (i.e.
through evaluation of survival and
causes of death); planning specific
interventions by national health
authorities; and obtaining epidemi-
ological data taking account of
recent migratory flows.
14 / March 2006
While Germany clearly boasts a
high quality healthcare system, the
TIF Delegation was aware that, as
in most countries where thalas-
saemia does not affect the indige-
nous population, the standard of
care varied across the country.
With the exception of specialist
centres such as Ulm and Hamburg,
treatment centres demonstrated
varying standards of medical care,
particularly in terms of applying
new protocols.
In short, the high dispersal of
patients with thalassaemia and
other haemoglobinopathies means
the field has limited appeal to med-
ical practitioners in Germany - in
terms of training as specialists, and
in terms of working to secure
greater financial support from
national medical authorities.
In addition to
measuring iron-load
in the liver & heart,
accurate tools are
needed to measure
the effects of iron on
other organs
TIF recommendations and
Action Plan
During a meeting with a number of
patient leaders, including Drs
Roland Fischer and Holger Cario of
the Ulm Association committee
and Dr Rosemary Behling from
Berlin, the TIF Delegation dis-
cussed ways to increase associa-
tion membership and help
resources go further, including by
merging with other rare anaemia
groups.
The Ulm Association, for example,
is run by a small number of dedi-
cated patient and parent volunteers
who live a considerable distance
from each other and work with
very limited resources. During its
Delegation visit, TIF therefore
made a commitment to help boost
the activities, profile and resources
of the association, working with it
to provide all patients in Germany
with the latest information on all
aspects of thalassaemia.
Next steps include:
1. Organising a field trip to
Germany for discussions with
local patients, doctors and hos-
pitals, to identify ways that TIF
can best support work in
Germany.
2. Establishing a national German
Thalassaemia Federation, to
guide and assist patients across
the country.
3. Organising a TIF workshop for
physicians - the first step in a
longer-term programme of con-
tinuous TIF medical training in
latest developments in thalas-
saemia, helping to encourage
young physicians to develop a
special interest in the disease -
along with a parallel patient/par-
ent workshop.
4. Translation of TIF material and
publications into German,
including those aimed at
i. health professionals,
ii. patients and parents and
iii. the public.
The high dispersal
of patients with
thalassaemia
means the field has
limited appeal to
medical practitioners
12th-15th December
2005
TIF Delegation
visit to Sri Lanka
The TIF Delegation to Sri Lanka was
made up of Shobha Tuli (TIF
President), Fatemeh Hashemi (TIF
Board Member), Loizos Pericleous
(former TIF Secretary and a thalas-
saemia patient) and Dr Matheos
Demetriades (TIF Project Officer).
The Delegation was accompanied
by Dr R.M. Mudiyanse, a TIF med-
ical collaborator and former head
of the thalassaemia treatment team
at Badulla General Hospital; Dr
Arambepola of the Kurunegala
National Thalassaemia Centre, who
is also a voting member of TIF; and
Mr and Mrs Amir Ejtehadi of the
Embassy of Iran in Sri Lanka.
TIF's first official Delegation visit to
Sri Lanka provided a thorough
overview of the status of thalas-
saemia, its prevention and treat-
ment in the country.
With a total population of around
20 million, Sri Lanka has 1,500-
2,000 patients with thalassaemia
(although other estimates put the
figure as high as 2,350 - see
below). According to the Ministry
of Health of Sri Lanka, the inci-
dence of b-thalassaemia is concen-
trated in four provinces, namely
North Western province
(Kurunegala and Chilaw), North
Central province (Anuradhapura),
Central province (Kandy) and Uva
province (Badulla), with a carrier
rate of approximately 3% across
these provinces. Government data
also indicate that the majority of
families are from lower socio-eco-
nomic groups and live in rural
areas.
Kurunegala National Thalassaemia
Centre in Kurunegala, the
Anuradhapura Treatment Centre
and Teaching Hospital in
Anuradhapura, the Badulla Treating
Centre in Badulla and Kandy
General Hospital in Kandy.
Kurunegala National Thalassaemia
Patient numbers high... and
Centre.
rising
Recent research has estimated car-
rier gene frequency in the Sri
Lankan population at 3%
(Weatherall, 2004), while inde-
pendent observers put the number
of transfusion-dependent thalas-
saemia major patients at 2,350 (de Anuradhapura Treatment Centre.
Silva’s et al, Lancet, 2000).
about 15% of the population are
The Ministry of Health estimates
carriers of ·-thalassaemia.
that 60-80 affected births occur
every year - a number that is
Sri Lanka's treatment centres
expected to rise unless an effective
prevention programme is imple- Visits to the main treatment cen-
mented. tres in the four provinces most
The average cost of treating exist- affected by thalassaemia enabled
ing patients is SR175,000 the TIF Delegation to see at first
($US2,465) per patient per year, hand the facilities provided to
totalling SR350 million - around 3% patients, as well as facilitating dis-
of Sri Lanka's total health budget cussions with patients, parents and

‚-thalassaemia is
concentrated in
four provinces,
with a carrier rate
of around 3%
In the course of their stay, mem-
bers of the TIF Delegation visited
the main treating centres in each of
the four provinces worst affected
by thalassaemia, namely the

Mrs Hashemi of TIF with children from the Anuradhapura Treatment Centre.

(1996 figures). These figures health professionals. A range of TIF

Mrs Tuli addressing the medical audi-
ence at Kandy General Hospital, Sri
Lanka.
exclude the cost of immunisation
programmes, screening pro-
grammes, screening blood prod-
ucts, managing complications, and
many other aspects of prevention
and care.
The most prominent forms of tha-
lassaemia in the country are two
severe forms of b-thalassaemia
major and one of HbE. The milder
form ‚-thal/HbE affects around
one-third of patients. In addition,
education material was distributed,
while TIF Delegation member Mrs
Hashemi pledged a quantity of
pumps to be sent from Iran, for dis-
tribution to patients at each centre.
Kurunegala National Thalas-
saemia Centre
The TIF Delegation was warmly
received by patients, parents and
health workers at the Kurunegala
National Thalassaemia Centre, all

March 2006 / 15
keen to discuss their experiences of
living and working with thalas-
saemia. The visit culminated in an
excellent music and dance per-
formance by patients.
Anuradhapura Treatment Centre
At the Anuradhapura Treatment
Centre, members of the TIF
Delegation met patients, parents
and health professionals in the tha-
lassaemia ward, providing an
opportunity to discuss the chal-
lenges they faced, as well as ways
in which TIF could offer support.
With the groundwork for a proac-
tive patient/parents association
already laid, TIF's ties with the tha-
lassaemia community in
Anuradhpura are expected to go
from strength to strength.
Kandy General Hospital tres, there was an extensive assess-
The TIF Delegation met a large ment of ways in which TIF could
number of paediatricians, haema- support Sri Lanka's Ministry of
tologists, physicians and laboratory Health in its efforts to strengthen
scientists involved in the treatment, prevention and treatment
prevention and diagnosis of thalas- prgrammes.
saemia at Kandy General Hospital. Main conclusions included TIF's
In the course of discussions, it was commitment to support the organ-
agreed that there was great
demand for an Educational
Workshop on the Clinical
Management of Thalassaemia and
a Nurses’ Workshop for carers of
patients with thalassaemia.
Roundtable at the Ministry of
Health
Another highly productive item on

TIF's ties with

Anuradhapura
are expected to
go from strength
to strength
Badulla Treatment Centre
At Badulla Treatment Centre, TIF
Delegates again focused on ways in
which TIF could support patients,
parents and health professionals.
Particular emphasis was placed on
finding ways to support patients
and parents seeking a more active
Mrs Hashemi, Mrs Tuli and Mr Pericleous at the Badulla Treatment Centre.
role in the Badulla Thalassaemia
Association, which is currently run
by health professionals. The TIF
Delegation encouraged parents to
join the Federation of Thalassaemia
Associations, in order to more
effectively lobby for adequate and
appropriate treatment for their chil-
dren.
Patients also took the opportunity
to discuss aspects of their care and the TIF Delegation agenda was a Dr Matheos Demedriades and Mr
roundtable session with the Loizos Pericleous of TIF with the partic-
issues of concern.
ipant patients of the social performance
Director-General of the Sri Lanka
at the Kurunegala National
Ministry of Health, Dr Thalassaemia Centre.
Kahandaliyanage. The discussion
was joined by medical advisers Dr isation of a National Thalassaemia
de Silva and Dr Somathunga Workshop in 2006, aimed at updat-
(Director of Non-Communicable ing health professionals on the pre-
Diseases), along with medical staff vention, diagnosis, screening and
from the College of Paediatrics and clinical management of thalas-
the College of Gynaecology at saemia. In addition, TIF has agreed
Colombo University. After dis- to integrate activities in the country
cussing key findings following TIF into its 3-year plan of action,
Delegation visits to the island's including establishing a Thalas-
main thalassaemia treatment cen- saemia Federation of Sri Lanka.

16 / March 2006

Thalassaemia after Dubai
T here is no doubt that the 10th
International Conference on
Thalassaemia and Haemoglo-
binopathies held in Dubai was one
of the most stimulating and inform-
ative yet. Presentations by the
world's leading authorities in the
field provided insight into cutting-
edge developments in a range of
research areas, including transfu-
sion safety, endocrinology and
chelation therapy - from patho-
physiology to new drugs to an
assessment of current therapies.
Here is a taste of issues discussed
of particular interest to those in the
field of thalassaemia.
Pathogen Inactivation Treatment
of Blood Components: A para-
digm shift in transfusion safety
Dr Laurence Corash, University of
California, San Francisco, CA, USA
The safety of blood transfusion has
substantially improved during the
last two decades, following the
implementation of stringent donor
screening and testing for particular
viruses. For example, nucleic acid
testing (NAT) has in many regions
reduced the residual risk of transfu-
sion-transmitted HIV and HCV
infections to one per several mil-
lion donations.1
However, the risk of bacterial con-
tamination remains, while other
pathogens, including emerging
viruses and protozoa, continue to
threaten the availability and safety
of blood supply, as well as under-
mining public confidence in blood
transfusion.2 Emerging pathogens,
such as West Nile virus (WNV),
emphasise the need for prospec-
tive strategies to ensure consistent-
ly effective blood safety. Moreover,
despite successes with NAT, virus-
es such as HBV may be present at
levels not detected by NAT, while
patients continue to expect a 'zero
risk' blood supply.3
At the same time, although the esti-
mated residual infectious risk per
donation for HIV, HBV or HCV is
lower than ever before, the cumu-
lative risk for all three viruses must
be considered - a risk that varies
from region to region (see table,
below). From the patient’s per-
spective, residual risk increases
with multiple transfusions, and
becomes significant for patients
requiring repeated transfusions
during intensive supportive thera-
pies, as in the care of patients with
thalassaemia.
The limits of 'reactive' screening
Testing to detect contaminating
pathogens in blood products is a
reactive approach to achieving
blood safety. Tests are routinely
performed for only a limited num-
ber of pathogens, while in the case
of some pathogens, existing tests
may be insufficiently sensitive to
detect low levels of contaminants
in the 'window period'. Equally,
tests may not be available when
pathogens, such as Chikungunya
and WNV, first emerge in donor
populations.4 In the United States,
for example, WNV was not identi-
fied as a transfusion-transmitted
pathogen for four years. And while
the time to develop and implement
NAT in the US was impressively
short, many transfusion-transmit
medical
focus
ted cases must have occurred
between 1999 and 2003.5 Even
after implementation of NAT, six
cases of transfusion-transmitted
WNV were reported.6 Thus, testing
alone will not prevent transfusion
transmission of emerging infec-
tious agents.
Screening for the future
Pathogen inactivation is a prospec-
tive approach to blood safety, suc-
cessfully implemented by the plas-
ma fractionation industry for more
than two decades. After the intro-
duction of pathogen inactivation
standards by global regulatory bod-
ies in the late 1980s and early
1990s, viral removal, solvent deter-
gent treatment and heat treatment
were widely incorporated into the
manufacturing process for plasma
fractions. As a result, there have
been no transmissions of HIV, HBV
or HCV by US-licensed plasma
derivatives such as albumin, AHF
and FIX since the end of 1987.
Until recently, pathogen inactiva-
tion has not been available for
labile (i.e. blood plasma) compo-
nents. For fresh frozen plasma, two
pathogen inactivation methods
received regulatory approval in the
1990s. One uses a combination of
a solvent and a detergent (S/D) to
disrupt lipid-enveloped viruses.
The drawbacks of the S/D method
are that non-enveloped viruses are
not inactivated, and the process
involves pools of 100 to 2,500
donors. The S/D treatment may
cause reduced levels of some anti-
thrombotic proteins reported to
result in thrombotic events, and has
been removed from some markets.
March 2006 / 17
The second method uses methyl-
ene blue and visible light (MB) to
modify both nucleic acids and the
surface structures of viruses. The
MB method can be applied to indi-
vidual units of plasma. The draw-
back of the MB method is that
intracellular or cell-associated
viruses are not inactivated.*
Several methods that target
pathogen nucleic acid have been
developed. The photochemical
treatment of platelets with amotos-
alen and UVA light has entered
clinical practice in some European
countries.* A similar system for
plasma has completed clinical test-
ing and is currently under
European regulatory review.*
Amotosalen/UVA inactivates a
broad range of viruses, bacteria
and protozoa in both platelets and
plasma. A system using riboflavin
and broadband UV light is being
developed to treat all blood com-
ponents, but only the platelet sys-
tem has started phase 3 clinical
testing in Europe. Pathogen inacti-
vation methods using PEN110 and
S303 for red blood cells have
encountered setbacks due to the
formation of antibodies to treated
red cells (RBCs). However, the
treatment process for S303 has
been modified with the goal of
eliminating the immuno-reactivity
of treated RBCs.* The modified
S303 process will soon re-enter
clinical testing in the US.
20/20 hindsight
If pathogen inactivation technolo-
gies for cellular blood components
had been available prior to the HIV
or WNV epidemics, the majority of,
if not all, transfusion-transmitted
cases could have been prevented.
So while there are some limitations
to the spectrum of inactivation,
these technologies offer the poten-
tial to improve blood safety, both
for known and emerging
pathogens.
In short, pathogen inactivation is a
practical and available technology
that represents the next step for-
ward in blood transfusion safety.
18 / March 2006
Residual viral risk post-NAT
Virus France12 Germany13
HIV 1:3,150,000 1:10,753,696
HCV 1:10,000,000 1:1,157,414
HBV 1:640,000 1:1,582,571
Cumulative risk 1:505,060 1:629,378
(HIV, HBV, HCV)
References
1. Goodnough LT: Risk of blood trans-
fusion. Anesthesiol Clin North
America 2005;23:241-252.
2. Morens DM, Folkers GK, and Fauci
AS: The challenge of emerging and
re-emerging infectious diseases.
Nature 2004;430:242–249.
3. Cyranoski D: Tainted transfusion
leaves Japan scrambling for safer
blood tests. Nat Med. 2004;10:217.
4. Quatresons I: Chikungunya out
break in Réunion, a French ‘over
seas département’. Eurosurveillance
Weekly Releases. 2006;Volume
11:Issue 1. http://www.eurosurveil-
lance.org/ew/2006/060126.asp#1.
5. Petersen LR and Epstein JS: Problem
solved? West Nile virus and transfu-
sion safety. N Engl J Med. 2005 Aug
4;353(5):516-517.
6. Centers for Disease Control and
Prevention. Update: West Nile Virus
Screening of Blood Donations and
Transfusion-Associated
Transmission – United States, 2003.
MMWR 2004;53(13):281-284.
7. Tabor E: The epidemiology of virus
transmission by plasma derivatives:
clinical studies verifying the lack of
transmission of hepatitis B and C
viruses and HIV type 1. Transfusion
1999;39:1160-1168.
8. Wagner SJ, Robinette D, Storry J, et
al: Differential sensitivities of virus-
es in red cell suspensions to methyl
ene blue photosensitization.
Transfusion 1994;34(6):521-526.
9. Osselaer JC, Doyen C, Sonet A, et
al: Routine use of platelet compo-
nents prepared with photochemical
treatment (INTERCEPT Platelets):
impact on clinical outcomes and
costs. Blood 2004;104(11):987a.
10. de Alarcon P, Benjamin R, Dugdale
M, et al: Fresh frozen plasma pre-
pared with amotosalen HCl (S-59)
UK14 US15
1:5,200,000 1:2,135,000
1:2,700,000 1:1,935,000
1:120,000 1:205,000
1:116,786 1:170,561
photochemical pathogen inactiva-
tion (PCT-FFP): transfusion of
patients with congenital coagula
tion factor deficiencies.
Transfusion. 2005;45:1362-1372.
11. Schott MA, Castro GM,
Stassinopoulos A: Modification of
the S303 RBC pathogen inactivation
process results in normal S-303
RBC viability in rabbits hyper-
immunized to S-303. Vox Sang
2005;89(suppl 1):138.
12. Pillonel J and Laperche S: Trends in
risk of transfusion-transmitted viral
infections (HIV, HCV, HBV) in
France between 1992 and 2003
and impact of nucleic acid testing
(NAT). Euro Surveill. 2005;10:5-8.
13. Seifried E, Roth WK. Prospective
survey of HCV, HBV, HIV-1 NAT
screening of more than 10 million
blood donors in the red cross blood
service centers in Germany.
Transfusion Clinique et Biologique
2002;8(suppl 1):17s.
14. Barbara J. Transfusion-Transmitted
Infections. Transfusion Alternatives
in Transfusion Medicine.
2002;4(2):42-47.
15. Dodd RY, Notari IV EP, Stramer SL:
Current prevalence and incidence
of infectious disease markers and
estimated window-period risk in
the American Red Cross blood
donor population. Transfusion
2002;42:975-979.

Disturbances of Iron Homeostasis
in Thalassaemias
I ron is one of the most common
elements in nature, an essential
component of proteins and
enzymes that plays an important
role in human metabolic processes.
In normal individuals, a series of
mechanisms operate to maintain
iron homeostasis (that is, to keep
iron levels relatively stable).
Disturbances in iron lead to iron
deficiency or iron overload, both of
which cause a wide spectrum of
clinical problems.
In thalassaemias, disorders of iron
homeostasis are characterised by
iron overload, often severe and
even fatal.
The following paper briefly discusses:
ñ The mechanisms of iron home-
ostasis
ñ The pathogenesis of iron
overload in thalassaemia
ñ The clinical manifestations of
iron toxicity
ñ The effectiveness of chelation in
prevention and treatment of iron
overload in thalassaemia
Iron homeostasis in brief
Under normal conditions, an aver-
age male has a total of 3-4gm of
iron. More than 60% of the total is
incorporated in haemoglobin (Hb)
and myoglobin, 25-30% is in the
liver and reticuloendothelial sys-
tem, and two minor but metaboli-
cally important fractions (of 0.3mg
each) - one bound to transferrin,
and the other being the iron that is
an essential constituent of proteins.
Iron-containing proteins fall into
two subgroups:
Dr Christos Kattamis, University of Athens
1. Haem iron compounds -
namely, haemoglobin, myoglo-
bin, cytochrome a, b and c,
cytochrome P450, catalase and
peroxidase
2. Non-haem iron compounds -
namely the NAD and succinate
dehydregenases, xanthine oxi-
dase and ribonucleotide
reductase
The rate of net
increase in iron
load is related to
the severity of
clinical phenotype
and to treatment
regime
These proteins utilise the ability of
iron to donate and accept elec-
trons, interconverting between fer-
rous and ferric forms, and are
involved in important metabolic
functions such as the transport of
oxygen (the main function of Hb),
oxidative energy production, mito-
chondrial respiration, the inactiva-
tion of harmful oxygen radicals and
the synthesis of DNA.
Understanding iron homeostasis
The basic steps of iron homeostasis
involve absorption, storage, ery-
thropoiesis (the production of red
blood cells), plasma iron turnover
and excretion. While the exact
mechanisms involved in these
processes are not yet completely
understood, scientific knowledge
on the subject is advancing rapidly.
For absorption, three regulatory
medical
focus
mechanisms are thought to operate:
1. The 'dietary regulator', in
which high intracellular iron
suppresses iron absorption
and the expression of the
DTM1 protein;
2. The 'storage regulator', which
controls iron uptake in
response to body iron stores,
and;
3. The 'erythropoietin regulator',
which modulates absorption of
iron in response to erythropoi-
etic activity.
Excess iron is stored in a) the
parenchymal cells of the liver, b)
the reticuloendothelial macro-
phages, which are loaded with iron
and supply most of the body's
usable iron by degrading Hb and
reloading transferrin with ferric
iron, and c) the enterocytes, which
are able to uptake, store and
excrete iron.
The most active tissue in the
metabolism of iron is the bone
marrow, in a process central to the
production of red blood cells. The
body requires 30-40mg of iron
daily (20 times the amount
absorbed from the diet) to produce
the huge number of red blood cells
(two million per second) needed
for the transport of oxygen. The
additional iron requirement is met
through the recycling of iron
released from Hb, and repeated
turnover of the transferrin iron
pool. Such is the body's demand
for iron that an individual atom is
estimated to remain in the circula-
tion for less than 90 minutes.
March 2006 / 19
(A number of new proteins with a
role in the regulation of iron metab-
olism have recently been identified,
although their specific function in
iron homeostasis remains under
investigation.)
Iron regulation in thalassaemias
The genetic defect that causes tha-
lassaemias affects the synthesis of
globin chains. In the case of ‚-tha-
lassaemia, the genetic defect caus-
es a variable reduction of ‚-chain
output, ranging from a minimal
reduction in very mild ‚+ thalas-
saemia mutations, to a complete
deficit of ‚-chains and ‚o thalas-
saemia alleles.
At the same time, the synthesis of
‚-chains continues normally. The
excess of ‚-chains accumulates
and precipitates within the precur-
sor cells, leading to intramedullary
destruction, ineffective erythro-
poiesis and severe anaemia, which
is further attenuated by peripheral
haemolysis.
The main pathogenetic mecha-
nisms of iron homeostasis that lead
to iron overload in thalassaemias
are due to ineffective erythro-
poiesis as a result of excess ·-
chains, defective iron utilisation in
the bone marrow, and increased
iron load in erythroblasts (early
stage red blood cells). Ineffective
erythropoiesis is accompanied by a
considerable increase in erythro-
poietic activity, as indicated by an
increase in serum transferrin
receptors (sTFRs). Increased ery-
thropoietic activity is followed by
increased marrow iron demand,
which is met by a relative increase
in plasma iron turnover (10 to 15
times above normal). Increased
plasma iron turnover, in turn, caus-
es transferrin saturation and the
circulation of non-transferrin
bound iron (NTBI), stimulating in
parallel increase in iron absorption
and iron overload.
The rate of net increase in iron load
in thalassaemia patients is related
to the severity of clinical phenotype
and treatment regime. In trans-
20 / March 2006
fused patients, the bulk of the
increase is due to transfusional iron
- an amount that is much higher
than the increase due to increased
iron absorption. It is estimated that
patients with thalassaemia major
receive an average of 30-40mg of
iron daily from transfusions alone.
Clinical studies have demonstrated
a positive relationship between
iron stores and units of blood
transfused. (For pictorial evidence
of this relationship, see Figure 1.)
In untransfused thalassaemia inter-
media (TI) patients, net iron load is
low. However, data on the degree
of iron load in untransfused TI
patients are limited and vary wide-
ly, because of the diversity in
severity of genotypes and pheno-
types, especially in populations
with a wide spectrum of mutations,
such as is found in Greece, where
30 mutations have been identified.
FIGURE 1
A recent study focused on the three
parameters of iron metabolism,
namely sTFR, NTBI and ferritin, in
29 untransfused patients with ‚-TI
molecularly characterised.
Based on clinical phenotype,
patients were divided into two sub-
groups:
Mild TI (group I), made up of 14
patients with moderate anaemia
(Hb>8g/dl), mild bone changes
and enlargement of the spleen.
Severe TI (group II), made up of 15
patients with moderate anaemia
(Hb>8g/dl) but with moderate to
severe bone changes and
splenomegaly. The majority of
patients in this group were
splenectomised.
The molecular characterisation
demonstrated interesting diversi-
ties and differences between the
two groups. In the genotypes of
mild TI, the co-inheritance of very
mild thalassaemia mutations pre-
vails and synthesis of HbA exceeds
50%. In contrast, in genotypes with
severe TI, the co-inheritance of ‰‚
(high F) , ‰‚ Corfu and ‚0, muta-
tions promoting HbF synthesis pre-
dominate. In this group, HbF was
very high, and in the majority of
patients HbA was not detected.
The data relating to the three
parameters of iron homeostasis are
also interesting, with all three
parameters found to be significant-
ly higher than in normal individu-
als. In addition, lev-
els of NTBI, sTFR
and ferritin were sig-
nificantly lower in
patients with mild,
as compared to
severe, TI. These
results indicate that
disturbances in iron
homeostasis are
positively related to
the severity of clini-
cal phenotype and
genotype. Another
interesting point was
the detection of
NTBI in patients with mild TI and
low iron load.
The concept of an anomalous
chelatable iron fraction in patients
with severe iron load when trans-
ferrin is completely saturated was
first advanced by Hershko et al.
They also reported the presence of
NTBI in patients with thalassaemia,
and studied the myocardial toxicity
of NTBI. The results of their work
demonstrated:
ñ Abnormal contractibility and
rythmicity of myocardial cells
ñ Loss of mitochondrial
respiratory enzyme activity
ñ Depletion of membrane PUFA number of recent studies examin- ing complications related to
(polyunsaturated fatty acid) ing the changing pattern of survival haemosiderosis, were introduced
ñ Increased lysosomal fragility in relation to chelation therapy. in the treatment of thalassaemias in
ñ Reversibility of toxicity compli- Data from seven Italian centres the 1970s. Approved drugs of cur-
cations through iron chelation with a total of 977 patients demon- rent clinical interest are deferoxam-
strate considerable improvement in ine (DFO), approved in 1960,
Clinical manifestations of iron survival rates in the younger cohort deferiprone (DFP), approved in
overload compared to the older, and in well- 1999, and deferasirox (Exjade, ICL
chelated (ferritin <1500ng/ml) 670), approved in 2005.
In transfused thalassaemia
compared to poorly chelated The properties of an ideal chelator
patients, the toxic effects of iron
patients (Borgna, Pignatti et al). are:
begin to appear during the second
Similarly, data from our own unit ñ Specific and high affinity for
decade of life, when the capacity of
relating to 647 frequently trans- ferric iron
plasma transferrin to bind iron is
fused thalassaemia major patients ñ High chelating efficiency
no longer sufficient, leaving NTBI
indicate that survival rates at the ñ Achievement of negative iron
to circulate in the plasma and pro-
age of 30 in the cohort born prior balance
mote the generation of free hydrox-
to 1975 was 73%, compared to ñ Tissue and cell penetration
yl radicals - propagators of oxygen
90% in the cohort born after 1975. ñ No iron redistribution
tissue damage - while insoluble
But the efficacy of chelation is per- ñ Oral administration
iron complexes are deposited in
haps best illustrated in Figure 2, ñ Long half-life
body tissues and end-organs, dis-
indicating that survival to the age of ñ Relatively non-toxic
rupting their function. The organs
40 is 87% in well-chelated (ferritin
most commonly affected are the
<2000ng/ml) patients, compared Of all the chelators mentioned
endocrine glands, the liver and the
to 29% in severely haemosiderotic above, Deferoxamine has been in
heart. The more common clinical
(ferritin >4000ng/ml) patients. longest use and had its efficacy
manifestations of iron load are
evaluated most.
stunted growth, hypogonadism,
Overall results in
disturbances of glucose metabo-
FIGURE 2 maintaining iron
lism, diabetes, myocardiopathy
load within safe lim-
(heart failure and arrhythmias), and
its in compliant
liver fibrosis and cirrhosis.
patients are satisfac-
In untransfused TI patients, the rate
tory. The main dis-
of iron accumulation is slow.
advantage, however,
Clinical manifestations are expect-
is the inconvenience
ed later in life, and are less frequent
of subcutaneous
and milder. In TI, clinical experi-
infusion and high
ence indicates minimal impairment
cost - factors con-
of growth and low incidence of
tributing to inade-
hypogonadism.
quate compliance.
The incidence and severity of com-
Detrimental effects
plications related to iron overload
on quality of life
in thalassaemia patients have grad-
have also been iden-
ually declined since the introduc-
Both studies also demonstrated a tified, including local discomfort,
tion of chelation therapy. The effi-
reduction in morbidity of iron com- sleep disturbances, work difficul-
cacy of chelation therapy in reduc-
plications in chelation-compliant ties, disruption of social and sexual
ing iron load and maintaining rea-
patients with low iron stores, and life, and others.
sonable and safe iron stores has
in the younger cohort of patients.
been documented by a number of
clinical studies. In the early period The toxic effects of
of DFO administration, it was
Similar results were also found in iron in transfused
shown that iron load, as expressed
by ferritin levels, was significantly
analysing the cause of death. In our thalassaemia
series of 115 deaths, 76.5% were patients begin to
lower in chelated compared to
associated with complications of
unchelated patients with the same
haemosiderosis, mainly myocar- appear during the
number of transfused units of
blood. There was also a positive
diopathies (71%) and liver diseases second decade
(6%). of life
relation between intensity of chela-
tion and reduction of iron load.
Effectiveness of chelation
The overall long-term efficacy of Another chelator, DFP, has a low
chelation has been evaluated in a Chelating drugs, aimed at prevent- molecular weight, an iron complex

March 2006 / 21
of 3:1 and a short half-life (45 to
120 minutes). It is slightly less
effective than DFO in achieving
iron balance in the relative dose of
75mg to 40mg/kg/day. However, it
is more efficient in removing iron
from the heart and the rare compli-
cation of agranulocytosis necessi-
tates close follow-up.
Clinical studies have demonstrated
that a combination of DFP and
DFO improved iron excretion,
while metabolic balance studies
showed additive or synergistic
effects, ascribed to a so-called
'shuttle' effect.
A clinical study of 60 patients indi-
cated that iron balance was
achieved in only a small percentage
(<20%) of patients treated with
monotherapy, increasing to 80% in
those treated with combination
therapy.
Clinical trials are still in progress to
confirm the advantages of combi-
nation therapy, which early find-
ings indicate may include:
ñ Each drug may access different
pools of iron
ñ An additive effect can be
expected
ñ Adjustment of ratio of chelators
to maximise efficacy in access-
ing different iron pools while
minimising toxicity
Iron balance was
achieved in only a
small percentage
(<20%) of patients
treated with
monotherapy,
increasing to 80%
in those treated
with combination
therapy
In contrast to DFO and DFP, clini-
cal experience of the two oral
chelators is limited, particularly in
the case of the recently-approved
Exjade.
Exjade is a tridentate iron chelator
with a prolonged half-life (8-16
hours) and excretion of chelated
22 / March 2006
iron in the faeces, taken once-daily
by oral administration.
According to two clinical trials
involving 586 thalassaemia major
patients and 184 patients with
myelodysplastic syndrome and
rare anaemias, Exjade is compara-
8th of
ble to DFO at half the dose, i.e. at
20 and 30 mg/kg/day.
Furthermore, the efficacy of Exjade
May
was related to daily iron input.
Thus, in patients with low iron
input (<0.3mg/kg), there was a
Internat
reduction in the mean LIC value,
even at doses of 10mg/kg/day,
while doses of 30mg/kg led to sig-
ional
nificant reductions in patients with
higher iron input (>0.5mg/kg/d). Thalass
Clinical studies have
demonstrated that a
aemia
combination of DFR
and DFO improved
iron excretion
In summary...
The clinical experience of chelation
indicates:
ñ No single chelator suits all
patients
ñ Patients failing with one drug
cannot be overlooked
ñ Age, body iron, disease state
and other factors must dictate
individual chelation regime
ñ Combination therapy promises
to be the most versatile
approach, delivering maximum
efficacy and minimal toxicity
ñ New oral chelators will modify
chelation treatment in the future
I would like to thank my colleagues
at St Sophia's Children’s Hospital
for their continuous efforts to help
patients and promote our research.

New Approaches to Iron Chelation
Thalassaemia Centre, Department
of Paediatric Haematology and
Oncology, University of Turin, Italy
M
ore than 30 years of research
has led to important advances
in iron chelation. One excellent drug,
deferoxamine (DFO), has been avail-
able for many years.
While intramuscular administration has
come to be regarded as inconvenient
and of low efficacy, the subcutaneous
slow infusion of DFO became standard
practice. Regular application of DFO
has been found to deliver an impressive
reduction in the prevalence and severi-
ty of iron-related clinical complications.
And experienced practitioners have had
success in limiting side effects and opti-
mising compliance in most patients.
Alternative treatment modalities,
including subcutaneous bolus injection
or intravenous continuous infusion,
facilitate treatment of a wide range of
conditions and special needs. Another
technique, using a DFO-starch polymer
combination, 40SD02, has recently
regained attention and is now in phase
II development. This method involves a
single intravenous infusion that results
in significant iron excretion lasting up
to several days, with limited side
effects.
Oral chelators to the fore...
Over recent years there have also been
impressive advances in the develop-
ment of new oral chelators.
Deferipone (DFP), or L1, is an orally
active chelator from the bidentate
hydroxypyridinones family, first syn-
thesised in 1982. However, the devel-
opment of L1 did not follow a system-
atic design and aspects of the drug's
safety and efficacy have prompted seri-
ous discussion and controversy.
Following the results of large controlled
studies, deferipone was approved in
Europe and many other countries, often
as a second line treatment for iron
overload. While the safety profile
requires close monitoring, the drug's
limitations are counterbalanced by ris-
ing evidence of a cardio-protective
effect where regular applied.
ICL670, a tridentate compound of the
triazols family, has recently been
approved by the US Food and Drug
Administration (FDA) for the treatment
of transfusional iron overload in
patients aged two years and above.
Overall results indicate that ICL670 is a
well-tolerated, effective oral chelator
that, taken once a day at a dose of 20-
30 mg/kg/day, is as effective as stan-
dard DFO administered subcutaneous-
ly. Preliminary results suggest a benefi-
cial effect on heart iron, both in animals
and humans.
A new oral chelator, GT56-252 or
Deferitrin, is now in phase II develop-
ment in patients with thalassaemia,
with encouraging results.
... along with combination therapy
The availability of more than one drug
helped prompt the search for possible
benefits of combination therapy, with
some in vitro data suggesting potential
additive and even synergistic effects.
Subsequent research involving patients
appears to have confirmed these initial
findings, although published data on
the subject is often uncontrolled and
very heterogeneous, and therefore
requires careful analysis.
A key problem is overuse of the term
'combination', describing a wide range
of treatment schemes that should be
more clearly distinguished. One
approach to a common terminology
could be the following:
ñ Mono-therapy: a single chelator is
prescribed and taken for more than
three months
ñ Alternate therapy: a single chelator is
administered in a single day, with two
chelators alternated on a weekly,
monthly or quarterly basis
ñ Combination therapy: prescription of
medical
focus
Dr Antonio Piga, Italy
more than one chelator, to be taken on
the same day for a significant part of the
treatment period. Two variants of combi-
nation therapy must be distinguished:
- Sequential: two chelators taken in
sequence on a single day, with no sub-
stantial overlapping of the two drugs in
the plasma
- Simultaneous or concomitant: two
chelators are taken at the same time,
with substantial overlapping of the two
drugs in the plasma
Combination therapy may potentially
be considered every time there is a
need for an additive or synergistic
effect, including the reversal of heart
disease. At the onset of heart disease, it
is important to provide full protection
from cardio-toxicity with continuous
treatment, minimising the presence of
non-transferrin bound iron (NTBI) in
the plasma. Intensive DFO chelation
with continuous intravenous infusion
has been demonstrated to be effective
in this regard. The addition of
deferiprone greatly enhances the effica-
cy and reduces the time needed to nor-
malise tissue iron levels.
Another potential application regards
patients with dose-related side effects
from DFO or DFP. In such cases, indi-
vidually tailored combination of the
two drugs may minimise side effects
while maintaining efficacy.
Finally, different types of combination
may be considered in the future,
depending on the different characteris-
tics of available chelators.
Another challenge facing specialists in
iron chelation is the full prevention of
iron-related complications. Recent
advances in diagnostics, as with
SQUID, MRI and NTBI, may offer a bet-
ter understanding of early iron overload
and toxicity, in turn allowing a rethink
as to when and how to start chelation
therapy in very young thalassaemia
patients, and those with milder condi-
tions such as thalassaemia intermedia.
March 2006 / 23
medical
on thalas-
saemia
focus
Deferasirox: An update on new
clinical studies on the oral chelator
Professor John Porter, Department of Haematology, University College London
D eferasirox (ICL670, Exjade)
was selected by Novartis
from over 700 compounds, identi-
fied as having suitable physico-
chemical properties for selective
iron chelation and a favourable bal-
ance between efficacy and toxicity
in preclinical iron animal models.
Preclinical laboratory studies
showed that this tridentate chelator
was more effective at removing
iron overload than deferoxamine
and deferiprone in the marmoset
model, with iron excretion occur-
ring by the faecal route.
Deferasirox also lacked mutagenic
and teratogenic effects on growth
reproduction.
The clinical development pro-
gramme has been a stepwise
process beginning with phase I
pharmacokinetics, which showed
dose proportionality and a long
plasma half-life of 11-19 hours,
suitable for once-daily dosing. This
was followed by iron metabolic
iron balance studies 1, which con-
firmed a faecal route of iron excre-
tion and suggested a once-daily
orally effective dose of 20-
40mg/kg/day in thalassaemia major
patients.
Once-daily oral
deferasirox
provides full
24-hour chelation
coverage with
potential protection
from non-transferrin
bound iron
Deferasirox has now been rigor
24 / March 2006
ously evaluated in multinational
phase II and phase III studies
involving more than 1,000 patients
with a diverse range of transfusion-
dependent anaemias, including
292 paediatric and adolescent
patients.
Studies have included a large scale
prospective randomised study in
586 thalassaemia patients (study
0107), including children over 2
years of age, comparing variable
doses of deferasirox with variable
doses of desferrioxamine, with
doses adjusted to baseline liver
iron concentration (LIC). Other
studies have included a ran-
domised prospective study in
patients with sickle cell anaemia
(study 0109) and a prospective
study in patients with myelodyspla-
sia and other anaemias associated
with transfusional iron overload
(study 0108).
In extension studies there is cur-
rently over three years of experi-
ence with deferasirox. Once-daily
oral deferasirox provides full 24-
hour chelation coverage with
potential protection from non-
transferrin bound iron (NTBI).
Deferasirox is effective in reducing
body iron with statistically signifi-
cant and clinically relevant reduc-
tions in both LIC and serum ferritin
at once-daily doses of 20-
30mg/kg/day. Changes in serum
ferritin broadly correlate with
changes in LIC, suggesting that
serum ferritin will be a valuable
tool for monitoring response to
deferasirox. The trends of changes
in LIC and serum ferritin are also
mirrored by dose-dependent
improvements in SGPT/ALT.
Pre-clinical laboratory and animal
data as well as preliminary clinical
data are consistent with access of
deferasirox to cardiac iron and
reduction of cardiac iron loading.
Deferasirox is generally well toler-
ated, with side effects including
gastrointestinal symptoms or skin
rash typically mild and transient. A
small non-progressive increase in
serum creatinine is seen in about
one-third of patients.
Deferasirox was recently approved
by the US Food and Drug
Administration (FDA) for the treat-
ment of transfusional iron overload
in adults and paediatric patients of
2 years and older. The cumulated
evidence from prospective and ran-
domised trials support the use of
deferasirox as an effective and well-
tolerated once daily monotherapy
for transfusional iron overload.
Deferasirox has
been rigorously
evaluated in
multinational phase
II and phase III
studies involving
more than 1,000
patients
Deferasirox:
Other contributions
Many research groups have been
examining various aspects of treat-
ment with deferasirox, attempting
to answer questions of practical
importance to the doctors and
patients who elect to use this form
of chelation.
One question is whether
deferasirox can be given with
safety and effectively to children.
This issue was tackled by a multi-
centre study involving centres in
Greece, Turkey, Tunisia, Belgium,
Italy and Germany, in which 154
children aged 2-15 years were
treated for one year and compared
to others given desferrioxamine
(Kattamis et al). The findings sug-
gested that the drug was well toler-
ated at all doses, with only a few
patients complaining of abdominal
pain, nausea, diarrhoea and/or skin
rash. The chelator was found to be
effective, as assessed by LIC, in all
age groups. The dose should be
adjusted to individual patient’s
needs, according to transfusional
iron intake.
Another multicentre study demon-
strated that growth and sexual
development was not disturbed in
children and adolescents (2-17
years) after 48 months of treatment
(Piga et al).
Another important question is
whether deferasirox is effective
in removing iron from the heart.
This question was the subject of
several studies, each taking a dif-
ferent approach. The first was by
Hebrew University in Israel
(Cabantchik et al), which assessed
the removal of labile cell iron by
deferasirox in the heart muscle
cells of mice, and from tissue cul-
tures. The study demonstrated that
the chelator gains relatively fast
entry into heart muscle cells and
scavenges labile cell iron.
Moving to a monkey model, a
group from the Children’s Hospital
of Los Angeles showed that
deferasirox and deferiprone were
equally effective in removing
stored iron from the hearts of ger-
bils (Wood et al). In humans the
drug was investigated in this
respect by a group from the
University Hospital in London
using MRI T2* to assess iron load
before and after treatment with LIC, tissue iron score and ferritin.
deferasirox (Eleftheriou et al). The After one year on either deferasirox
study involved 22 patients (17 with or DFO, there was a reduction in
thalassaemia major, five with other measurements, indicating that both
conditions), treated for 12-18 these chelators are effective in the
months. The pre-treatment geo- presence of fibrosis.
metric mean was 18 months rising
to 23 months, leading to the con-
clusion that deferasirox is effective
at chelating iron from the heart.
Since liver iron concentration (LIC)
was used to assess the effective-
ness of deferasirox in most studies,
its efficacy in removing liver iron
has been established. However,
further research was needed to
establish the effectiveness of chela-
tion looking, for example, at liver
pathology.
In a multicentre study involving
555 transfusion-dependent
patients at centres in France, Italy,
Belgium, the US and Argentina, a
liver biopsy was performed before
and after one year on deferasirox
and desferrioxamine, with histol-
ogy graded according to the Ishak
method (Turlin et al). Changes in
grading were seen with both drugs,
especially at higher doses, and
there was a reduction in liver
inflammation and improved liver
function.
The drug is generally
well tolerated, with
side effects including
gastrointestinal
symptoms typically
mild and transient
This approach was taken one step
further in another multicentre
study involving centres in Italy,
Canada, France, Turkey and the
US, in which the efficacy of
deferasirox in patients with
advanced fibrosis of the liver was
compared, again, with the efficacy
of desferrioxamine (Angelucci
et al).
Researchers selected patients with
advanced fibrosis (Ishak score of 5
or 6), assessing their iron load by
March 2006 / 25
 thalas-
medical
on
Deferiprone versus desferrioxamine:
focus

Preliminary results of a randomised

clinical trial in patients with
haemoglobinopathy
Professor Aurelio Maggio, A. O. ‘V. Cervello’, U.O.C. Haematology II, Palermo, Italy
of the study are:

S ickle cell anaemia and

‚-thalassaemia intermedia
patients are found in consider-
able numbers in many countries.
One in 600 African-Americans
has sickle cell anaemia, with
2,000 affected children born each
year. A total of 9% of African-
Americans carry the sickle cell
trait. In Italy, 928 cases of sickle
cell anaemia were registered in
2000, and while there is no reli-
able data on the prevalence of
thalassaemia intermedia, it is
estimated that 25% of haemoglo-
binopathy patients could have
this phenotype.
Evidence of severe iron overload-
ing in sickle cell anaemia and tha-
lassaemia intermedia has been
demonstrated by several authors.
At the same time, the safety of
oral chelation in the treatment of
both diseases has been well
understood since 1994.
Nonetheless, the Society for the
Study of Thalassaemia and
Haemoglobinopathy faced con-
siderable difficulty organising a
randomised multicentre clinical
trial for thalassaemia. However,
results of the first phase, which
lasted one year and began three
years ago, have now been
released.
The RCT3 Haem Trial was an
independent randomised clinical
trial comparing the efficacy of L1
(75mg/kg/day) vs DFO
(50mg/kg/day) in sickle cell
anaemia, sickle cell/‚-tha-
lassemia and thalassaemia inter-
media, in patients with ferritin
levels of 800-3,000ng/ml. The
expected duration of the study
was five years.
The main outcome of the study
ñ No evidence of difference in
efficacy between the two groups
was the difference between ñ No detection of agranulocytosis
serum ferritin concentrations. or granulocytopoenia in either
Secondary outcomes were varia- group - not in subjects simulta-
tions in liver iron concentration, neously treated with hydrox-
and liver and heart iron content yurea (13-14mg/kg)
measured by nuclear magnetic ñ Final ferritin levels significantly
resonance.
A total of 133 patients were ran- lower in patients treated by
domised, with 56 receiving L1 chelation and hydroxyurea
and 45 receiving DFO. These 101 (possible control of bone
patients were evaluated after one marrow expansion?)
year of treatment, and the results
compared from a clinical, haema- The recruitment of patients is con-
tological and biochemistry per- tinuing and the trial is open to cen-
spective. tres outside Italy. For more infor-
The two groups showed no dif- mation, please contact the author
ference in ferritin concentrations by email at aureliomag-
after one year of treatment, and gio@virgilio.it
differences in rates of withdrawal
and failures of treatment were
not statistically significant. No
cases of agranulocytosis were
detected. Patients treated with
hydroxyurea and L1 had lower
ferritin levels after one year of
treatment, and hydroxyurea treat-
ment had no impact on the fre-
quency of side-effects in either
group.
Overall, preliminary conclusions

26 / March 2006
 medical
focus
TIF Awards 2006
10th International Conference on Thalassaemia and Haemoglobinopathies
and 12th International TIF Thalassaemia Conference for Patients and Parents
Dr Michael Orford

I n the course of each bi-annual

Thalassaemia International
Conference, it has become an
resulted in a dramatic reduction
in the number of patients born
with this severe disease and addi-
institution to award two prizes to tionally worked to provide a bet-
individuals with outstanding con- ter quality of life for those already
tribution to Thalassaemia affected."
Worldwide. The first is the "Panos
Dr. Michael Orford
Englezos" prize which is awarded
to a scientist for his/hers excep-
tional contribution in the field of
Thalassaemia research and the
"George Englezos" prize which is
awarded to a person-non-scien-
tist, for his/hers outstanding con-
tribution in the promotion and
control of thalassaemia around
the world.

The International Conference in

Dubai this year was no exception.
In the course of this Conference
two outstanding personalities
were awarded the above-stated
prizes. The late Dr. Panos
Ioannou was awarded with the Mr Mahesh Kotecha, receiving the ‘George Englezos’ prize from Mr
Panos Englezos and Mr Robert Ficcarra.
‘Panos Englezos’ prize for his
invaluable contribution in the
fight to finding a cure for
Thalassaemia, while Mr. Mahesh,
from Malawi – Africa, was award-
ed the ‘George Englezos’ prize
for his multifaceted social contri-
bution in the promotion of
Thalassaemia.

"Dr. Panos Ioannou, a prominent

scientist was very influential to
many and dedicated his working
career to help patients suffering
from many genetically inherited
diseases, especially thalassaemia.
One of his very first activities was
the setting up the prenatal diag-
Mr Andreas Ioannou, receiving the ‘Panos Englezos’ prize on behalf
nosis programme for thalas- of his father late Panos Ioannou. Beside him, Mr Panos Englezos and
saemia in Cyprus, which has Mr George Constantinou (Former TIF President).

March 2006 / 27
 in thalassaemia
coming
events
Forthcoming Events
Antalya, Turkey
23rd-27th April 2006
4th International
Thalassaemia
Summer School
(ITSS)
T he 4th biannual International
Thalassaemia Summer School
(ITSS), co-organised by Turkey's
Ministry of Health and the
Thalassaemia Federation of Turkey,
will be held at the Atlantis Resort
Hotel in Antalya, under the aus-
pices of Turkey's Minister of
Health, Professor Dr Recep Akdag.
Since its establishment in 2000,
ITSS has provided a forum for
patients, parents and health profes-
sionals to come together to discuss
latest developments in the preven-
tion, diagnosis, screening and clini-
cal management of thalassaemia, as
well as offering an opportunity to
share problems and seek solutions.
Subjects to be covered at this year's
event include:
ñ Epidemiology and Prevention of
Thalassaemia
ñ Genetics of Thalassaemia
ñ Preimplantation Genetics
ñ Blood Transfusion
ñ Iron Overload
ñ Chelation Therapy
ñ Complications in Thalassaemia
ñ Stem Cell Transplantation in
Thalassaemia
ñ Psychosocial Problems in
Thalassaemia
ITSS is an important forum for shar-
ing latest developments, airing con-
28 / March 2006
cerns and seeking help. But it also
offers something more -- a sense of
hope.
As Professor Canatan, President of
the Thalassaemia Federation of
Turkey and President of the ITSS
2006 Organising Committee, says,
"The first ITSS meeting was when
patients and parents first became
aware that they were not alone and
joined together to become one
voice."
With each subsequent meeting,
that sentiment has only grown
stronger.
For more information, visit
www.talasemi.org
Source: www.talasemi.org
Vienna, Austria
26th-30th April 2006
41st Annual
Meeting of the
European
Association for
the Study of the
Liver (EASL)
T he annual meeting of the
European Association for the
Study of the Liver (EASL) will be
held at the Austria Centre Vienna,
on 26th-30th April 2006, under the
auspices of the Honorary President
of EASL, Professor Juan Rodes.
EASL is one of the world's leading
associations for clinicians and sci-
entists involved in the fight against
liver disease - reflected in the ever-
increasing number of participants
attending its annual meeting, and
the wide range of research inter-
ests covered.
This year’s programme has been
expanded to include joint meetings
of EASL/ELITA and EASL/viRgil.
EASL 2006 also features an exciting
two-day postgraduate course on
hepatitis C virus immunology, with
a focus on:
ñ Immunological phenomena in
Hepatitis C
ñ The role of the adaptive immune
responses in protection and
damage
ñ Manifestations of altered immu-
nity in Hepatitis C
The core of the EASL 2006 Meeting
will comprise four General
Sessions and 12 Parallel Sessions,
with two mornings given over to
eight parallel workshops. A num-
ber of industry-sponsored satellite
symposia will also be held through-
out the course of the meeting.
Meanwhile, the EASL 2006
Scientific Programme has been
expanded, kicking off with an
Inaugural Poster Session in which
participants are invited to join in
informal discussions with poster
presenters. The Scientific
Committee has also extended the
deadline for submission of
abstracts, enabling participants to
include their most recent data.
For more information, visit
www.easl.ch/easl2006
Source: www.easl.ch
European School of
Genetic Medicine,
Bertinoro di Romagna,
Italy
26th April-2nd May 2006
19th Annual
Course in Medical
Genetics
T he European School of Genetic
Medicine is organising its
annual course in Medical Genetics,
at the University Residential Centre
in Bertinoro, Italy.
This prestigious course is tailor-
made for scientists and health pro-
fessionals involved in genetic
research. The scientific programme
covers all aspects of Medical
Genetics, with main sessions
covering:
ñ Introduction to Genetic Analysis
ñ Clinical Genetics
ñ Functional Biology
ñ Cancer Genetics
ñ Genomic Variability
ñ From the Clinic to the Lab
ñ New Perspectives
Workshops will run concurrently,
with ample time for discussion and
questions-and-answer sessions.
Further information on the Medical
Genetics Course and other courses
due to be held in 2006 can be
accessed via the European
Genetics Foundation website at
www.eurogene.org
Source: www.eurogene.org
The Egyptian Thalas-
saemia Association, Egypt
8th-9th May 2006
7th International
Thalassaemia
Conference for
the 8th of May
(E.T.A.)
T he Egyptian Thalassaemia
Association has announced that
the 7th International Thalassaemia
Conference marking the 8th May,
International Thalassaemia Day,
will be held at the Nile Hilton in
Cairo on the weekend of 8th & 9th
May 2006.
The President of the Conference,
Professor Amal El Beshlawy, said
particular aspects of the clinical
management of thalassemia will be
covered, including: Updates in
Gene Therapy, Stem Cell
Transplantation, Iron Overload and
Iron Chelation Therapy, Puberty
and Pregnancy in Thalassaemia,
Transfusion Medicine Update,
Genetics of Thalassaemia, Prenatal
Diagnosis and Prevention of
Thalassaemia and finally, discus-
sion sessions for patients and
doctors.
A number of international speakers
will be participating in the confer-
ence. Abstracts are requested by
8th April 2006 at the latest.
Abstracts will appear on TIF’s web-
site in June 2006.
Bern, Switzerland
12th-13th June 2006
IPFA/PEI 13th NAT
Workshop on
‘Surveillance and
Screening of Blood
Borne Pathogens’
T he I n t e r n a t i o n a l P l a s m a
Fractionation Association
(IPFA), together with the German
Paul-Ehrlich-Institut (PEI) – the
German Federal Institute for Sera
and Vaccines - is co-organising the
13th IPFA & PEI Workshop on
Nucleic Acid Amplification Testing,
which is to be held on 12-13 June,
2006 at the Allegro Kursaal in Bern,
Switzerland.
Over the years, the NAT
Workshops have become a leading
international annual event for dis-
cussion and assessment of
progress made in the development
and implementation of NAT-testing
and other screening technologies.
The workshop now represents an
identified body of expertise, which
provides direction for emerging
applications of NAT-testing and
issues related to blood safety in
general.
The programme of the Workshop
will incorporate the following
sessions:
1. Keynote Address: Is it safe? Is it
sound? Ethical Considerations in
Policies Regarding Blood Safety
2. Session One: Blood Screening:
Harmonisation or Diversity?
3. Session Two: Global Issues
(Eastern Europe, S.E. Asia, South
Africa)
4. Session Three: Hepatitis B: The
Emerging Picture, Experience
with Anti-Core Testing
5. Session Four: Additional
Markers: Cell Associated
Viruses, Vector Borne Viral
Infections
6. Session Five: Progress in Prion
Testing
7. Session Six: New Technologies
& their Application to Blood
Screening
8. Session Seven:Improved tech-
March 2006 / 29
 nologies and Screening Plat
forms
9. Session Eight: Effective Utilisa-
tion of Sample Repositories
Ample time will be allocated for
discussion and debate.
Further information regarding the
Workshop is available on the IPFA
website: www.IPFA.nl
Source: www.IPFA.nl
Paris, France
1st-5th July 2006
12th International
Symposium on
Viral Hepatitis and
Liver Disease
(ISVHLD)
F ollowing highly successful pre-
vious meetings in Houston,
Tokyo, Rome, Atlanta and Sydney,
the 12th International Symposium
on Viral Hepatitis and Liver Disease
(ISVHLD) is to be held at the Palais
des Congrès in Paris, France from
1st-5th July 2006.
Event proceedings will cover the
full range of issues, from state-of-
the-art treatment protocols to con-
troversies in the field - guarantee-
ing a full and varied programme.
A key feature of ISVHLD 2006 will
be the presentation of original
studies, in plenary sessions, sym-
posia, parallel workshops and
poster sessions. Conference organ-
isers have also allowed for the
inclusion of late-breaking data
along with satellite symposia, while
the final day will focus on
Hepatitis-HIV co-infections, in a
joint session with the French
Aids/Hepatitis research agency,
ANRS.
In addition to regular discussion
topics, including known viruses
and possible new candidates
involved in viral hepatitis at the
basic, clinical and therapeutic lev-
els, conference participants will
also hear new data on HAV and
HEV, with a focus on epidemiolo-
gy, immunology and vaccines.
A great deal of new data on HBV
30 / March 2006
and HCV will also be presented,
including on epidemiology, virolo-
gy, diagnostic tests, chronic liver
disease, hepatocellular carcinoma,
liver failure and transplantation,
actual and future therapies and
vaccines. Pathogenesis will encom-
pass animal models, cellular,
humoural and innate immunity, as
well as immunotherapeutic
approaches. Special consideration
will be given to the fast progress of
antiviral molecules and the ongoing
battle against viral resistance.
Source: www.isvhld2006.com
Cape Town, South Africa
2nd-7th September 2006
29th International
Society of Blood
Transfusion (ISBT)
International
Congress
F or the first time in its history,
the biannual International
Congress of the International
Society of Blood Transfusion (ISBT)
will this year be held in sub-
Saharan Africa. Co-organised by
the South African Blood Alliance
and the Africa Society for Blood
Transfusion in collaboration with
ISBT, Congress delegates will gath-
er at the Convention Centre in
Cape Town, South Africa on 2nd-
7th September 2006 - offering an
excellent opportunity to combine
professional development with a
unique tourist experience.
As well as covering the latest scien-
tific developments and clinical
practice in transfusion medicine,
the ISBT Congress will feature edu-
cational programmes, symposia,
plenary sessions and concurrent
sessions on a range of additional
issues, including a focus on coun-
tries with less developed blood
transfusion services.
ISBT Congresses attract interna-
tional speakers of world renown -
reflecting the high standing of ISBT
itself. Founded in 1935, ISBT is a
leading scientific society represent-
ing specialists in blood safety and
transfusion medicine from more
than 85 countries. In addition to
ISBT's International Congresses,
held every two years, professionals
in the field are also supported by
Regional Congresses, held each
alternate year.
To view a preliminary programme
for ISBT's 2006 International
Congress, visit www.isbt-
web.org/capetown/programme.
Source: www.isbt2006.com
Nicosia, Cyprus
7th-11thNovember 2006
10th
International
Course on
Thalassaemia
and other
Haemoglobin
Disorders
T he Thalassaemia International
Federation is due to host the
10th International Course on
Thalassaemia and other
Haemoglobin Disorders in
November 2006.
A six-day state-of-the-art course
covering all aspects of the preven-
tion and management of thalas-
saemias and other severe haemo-
globin disorders, this annual
course is led by internationally
acclaimed experts in the field,
offering participants access to a
truly world-class faculty.
As in previous years, candidates
may apply for TIF sponsorship to
attend the course. Every effort will
be made to accommodate suitable
candidates, however please note
that sponsorships are limited.
Application forms are available
from the TIF website at www.tha
lassaemia.org.cy.
Please note: The 11th International Conference on Thalas-saemia
Applications should be submitted and Haemoglobi-nopathies and the 13th International
as soon as possible to secure a TIF Conference for Thalassaemia Patients and Parents
place on this important course.
Course dates will be posted on the
TIF website. INVITATION TO HOST
The American Society of
Haematology (ASH)
Orlando, Florida, USA
9th-12th December 2006

48th Annual
Meeting and
Exposition
T he next meeting of the
American Society
Haematology (ASH) - an annual
of

meeting that has fast become one

of the most important events in the
field - is scheduled to take place on
9th-12th December 2006, at the
Orange County Convention Centre
in Orlando, Florida.
Every year the four-day meeting
attracts around 20,000 clinicians,
scientists and others from around
the world, gathered to discuss crit-
ical issues in haematology.
A superb educational programme
combined with cutting-edge scien-
tific sessions includes oral and
poster presentations, chosen by
F ollowing the outstanding success of the January 2006 joint
International Conference on Thalassaemia and Haemoglobi-
nopathies and the International TIF Conference for Thalassaemia
peer-review, as well as plenary Patients and Parents, the Thalassaemia International Federation
symposia and lectures on spe- invites parties interested in hosting the joint 2008 conferences to
cialised areas of haematology. A submit a proposal.
parallel state-of-the-art exposition Interested parties can download guidelines and prerequisites from
featuring exhibits by pharmaceuti- the TIF website at www.thalassaemia.org.cy.
cal companies, medical suppliers,
clinical diagnostic and research- The International Conference on Thalassaemia and Haemoglobi-
based companies, publishers and nopathies and the International TIF Conference for Thalassaemia
non-profit organisations comple- Patients and Parents are together the biggest and most important
ments a scientific programme event in the field of thalassaemia and other haemoglobin disorders.
focused on latest developments in Organised every two years, these joint conferences provide an
scientific research. essential forum for patients, parents and medical scientists to
For more details about the exchange information on latest findings and best practice.
ASH 2006 Meeting, visit
www.hematology.org.

Source: www.hematology.org

March 2006 / 31
 on thalassaemia
publica
-
tions

Prevention Book, Vol.2

Order your copy V olume II of a two-volume

series on prevention -
Please fill in the order form below
and post or fax it along with your
of TIF’s latest “Prevention of Thalassaemia and payment. Please send your order

publication now! other Haemoglobin Disorders” - is

now ready for distribution. The book
form along with payment to:

is the work of international experts in Thalassaemia International

the field, and promises to be an Federation (TIF)
invaluable guide to those working P.O.Box 28807, 2083 Nicosia
towards the prevention of thalas- 31 Ifigenias Ave., 2007 Nicosia
saemia. Cyprus
Tel: +357 22 319129
The book is available free of charge Fax: +357 22 314552
from the publishers, the Thalas-
saemia International Federation. E-mail: thalas-
Postage is charged at US$15 for one saemia@cytanet.com.cy
book and US$20 for two books,
payable by cheque made out to the Website:
Thalassaemia International Fede- http://www.thalassaemia.org.cy
ration or by Visa, Mastercard or
American Express.

Prevention Book, Vol. 2 - Order Form

Number of books required:
One book (US$15) q Two books (US$20) q

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Address:

City:

Country: Postal Code:

Medical speciality:

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Cheque q Visa q Mastercard q American Express q

Card Number: Expiry date:

Signature:

32 / March 2006

Other TIF Publications
Latest Publications:
publica
-
tions
effective prevention of thalassaemia.
As such, it represents a major step
towards a fundamental goal of the
Thalassaemia International Fede-
ration (TIF) -- that is, to establish pre-
vention programmes based on the
same high standard of best practice In
in every country of the world. English.

Distribution of Other
Educational Material
“About Thalassaemia”
Since October 2003
“Compliance to Iron
Chelation Therapy
This is an illustrated book, carefully
designed to cover the needs of
with Desferioxamine”
patients and parents. The book is
being translated into 10 languages of In English, Greek, Italian, Spanish,
affected countries.
Updating of existing Arabic, Farsi
publications:
“Guidelines for the
Clinical Management
of Thalassaemia” and
“Blood Kit” “Guidelines for Home
“Prevention of Update planned for 2005. Infusion of Desferal”
Thalassaemia and
In English, Portuguese, Italian
other Haemoglobin
Disorders”
Book Volume 1
Since July 2003
In English,
Greek,
This publication provides a thorough Spanish,
overview of all the issues involved in Arabic, Farsi
the establishment of policies for

March 2006 / 33
 world -
thalassaemia
wide
News from Around the World
Shahbaz Social
Welfare Association,
Larkana, Pakistan
By Gul Sher Mangi,
General Secretary
Blood Safety
and Prevention
of Thalassaemia
A s part of its effort to improve
awareness of thalassaemia, its
treatment and prevention, the
Shahbaz Social Welfare Association
recently organised a one-day work-
shop on Blood Safety and Prevention
of Thalassaemia, in collaboration with
Hussaini Blood Bank and the Health
Department of the Government of
Sindh province. The event was held on
16th January 2006, at the Paris Inn
Hotel, Larkana.
A central theme was the challenge of
providing a greater number of blood
banks, of international standard.
Speakers highlighted World Health
Organisation criteria for securing the
safe and sufficient supply of blood,
including an emphasis on regular, vol-
untary blood donation.
Speakers included Dr Zahid Ansari,
Programme Manager, Sindh Safe
Blood Transfusion Authority; Dr
Sarfraz H. Jafary, Project Director,
Global Fund; Dr S. A. Mujeeb, head of
the Central Laboratory (JPMC),
Karachi; Gulsher Mangi, General
Secretary, SSWAL, Larkana; Dr Syed
Mahboob Shah, Managing Secretary
(CMCH) Larkana; and Ghulam Sarwer
Chandio.
Speakers also emphasised the active
role to be played by the community in
encouraging blood screening for a
number of diseases, including thalas-
saemia.
34 / March 2006
A total of 218 applications have been
made to register blood banks, from
across the province. So far, 20 blood
banks have been approved at the local
level, with a further 12 district blood
banks to be upgraded.
Highlighting the role of thalassaemia
associations in securing adequate,
safe blood, speaker after speaker
referred to associations' role in raising
community awareness of thalas-
saemia, and to emphasise the impor-
tance of blood screening.
Rezvan Ghaderi, FARS
Thalassaemia Society,
Iran
A message of
concern
R ezvan Ghaderi is Chief Editor of
'Hope', a newsletter produced
by the FARS Thalassaemia Society. In a
recent column, she made a heartfelt
plea for a change in attitudes to tha-
lassaemia.
An essential need of all human beings
is to feel happy and healthy. An
upbeat mood directly influences peo-
ple, raising their self-confidence.
In thalassaemia patients, the effect of
mood and social activities on the
improvement of physical status is a
controversial issue, which has occa-
sionally been forgotten or neglected.
But it is obvious that mood has an
indirect impact on haemoglobin lev-
els, because when thalassaemia
patients are happy, they follow their
treatment better... and less well when
they are depressed.
Yet the government of Iran is more
concerned with delivering proper
therapy than improving public under-
standing about thalassaemia - an issue
that should be at the top of the gov-
ernment agenda.
The mass media - particularly televi-
sion - could play a significant role in
improving public awareness. Most
people in Iran have heard of thalas-
saemia, but do not know exactly what
it is. To them, thalassaemia means pal-
lor, dysmorphic features, blood trans-
fusion.
But is that all thalassaemia is about?
Why, for example, do people not think
of clever children when they hear the
word thalassaemia?
The reason is that the only appearance
thalassaemia makes in the media is on
International Thalassaemia Day, with a
downbeat television news item show-
ing a child receiving a blood transfu-
sion, looking disappointed and
depressed.
This is the public image of thalas-
saemia.
Because we do not show off and pro-
mote the abilities rather than the
weaknesses of thalassaemia patients,
they are denied their rightful place in
our society. They find it difficult, for
example, to convince employers who
are unaware of those abilities.
So whenever a drawback of thalas-
saemia is raised, five strengths of tha-
lassaemia patients must follow, eras-
ing the negative effects of that single
negative point.
Thalassaemia is a reality and, bitter-
sweet or not, it is a fact that must be
accepted.
For its part, the government should
provide opportunities to thalassaemia
patients, so that they can reach their
full potential. Our patients with thalas-
saemia can be motivated through love
and affection. But they also need to be
given the opportunity to be employed,
giving them hope for a promising
future.
It is our duty to change attitudes, and
focus on the positive aspects and abil-
ities of patients with thalassaemia.
Provided by
ViennaLab, Austria
New laboratory
technology
New Alpha-
Thalassaemia
Test-Strip Assay
I n normal adults, 97% of total
haemoglobin is a-haemoglobin
(HbA), which consists of two a-
haemoglobin chains and two b-
haemoglobin chains. The remaining
3% of total haemoglobin is HbA-2 (·-
chains combined with ‰-chains) and
HbF (foetal haemoglobin).
The human ·-globin gene cluster is
located on chromosome 16 and spans
about 30 kb, includes the following
five loci: zeta; pseudozeta; pseudoal-
pha-1; alpha-2; alpha-1. The alpha-2
(HBA2) and alpha-1 (HBA1) coding
sequences are identical.
·-thalassaemias are the result of dele-
tions and/or point mutations in each
of the ·-genes, as well as deletions of
both HBA2 and HBA1, respectively.
More than 200 mutant alleles have
been characterised, some of which
cause structural abnormalities of the
·-globin molecule, such as haemoglo-
bin Constant Spring. Others may lead
to dysfunctional synthesis of haemo-
globin, such as haemoglobin H or
haemoglobin Barts hydrops foetalis.
All these disorders are a major public
health problem, particularly among
populations of Mediterranean, Asian
and African origin.
For the large majority of affected indi-
viduals, there is only supportive man-
agement of the disease but no defini-
tive cure. As a consequence, health
authorities focus on prevention pro-
grammes based on heterozygous car-
rier screening and prenatal diagnosis.
Since only a few ·-globin alleles are
prevalent in each at-risk population,
large-scale population screening pro-
grams are feasible. However, these
require simple and automated test
procedures.
By offering easy-to-handle StripAssays
for haemoglobinopathies, ViennaLab
helps healthcare organisations and
test laboratories identify carriers and
individuals affected by the disease in
question. Indeed, the ·-Globin
StripAssay detects >95% of all HbA
mutant alleles commonly found in
Mediterranean countries and >99% of
all those reported in the Middle East
and South East Asia.
The ·-Globin StripAssay covers 21 of
the most frequent ·-globin mutations
on two teststrips- A and B. The muta-
tions include Hb Constant Spring, Hb
Adana, Hb Quong Sze, Hb Icaria, Hb
Pakse and Hb Koya Dora.
Principles of the assay
The ·-Globin StripAssay uses two test
strips - A and B. Their function is
based on the reverse-hybridisation
principle, and the assay provides all
necessary material for completion in
four easy steps:
ñ Rapid isolation of genomic DNA.
Convenient from easily obtained
body samples (blood, amniotic
fluid, buccal swab)
ñ Easy multiplex PCR-amplification of
·-globin sequences of interest.
Simultaneous biotin-labelling
ñ Precise selective hybridisation of ·-
globin sequences of interest onto
StripAssay. Mutant and wild-type
probes on StripAssay
ñ Clear identification of hybridised ·-
globin sequences of interest only.
Biotinylated sequences detected by
streptavidine-alkaline phosphatase
Principal results
For each polymorphic position, one of
three possible staining patterns may
be obtained:
1. Wild type probe only: normal
genotype
2. Wild type and mutant probe:
heterozygous genotype (carrier)
3. Mutant probe only: homozygous
mutant genotype (affected)
Note to laboratory personnel:
Some of the mutations covered by the
·-Globin StripAssay are located within
a few nucleotides on the ·-globin
gene. On the test strips these are rep-
resented by a common wild type
probe. Therefore 21 mutations are
covered by nine wild type probes
only.
Further StripAssays are available for:
ß-globin (thalassaemia), cardiovascu-
lar diseases, familial Mediterranean
fever, Gaucher disease, haemochro-
matosis, pharmacogenetics, cancer
(methylation) and sugar intolerance
(lactose, fructose).
Source: www.viennalab.com
For more information, visit the
ViennaLab website at
www.viennalab.com
By Francesca Pieragostini
It’s a boy!
M y son AJ was born at 6 lbs 8 oz,
with a full head of hair! The
moment I held him in my arms and
looked over at my husband, I knew
my world was complete.
As the first woman with thalassaemia
major to have a child at New York
Hospital, I am proud to share my
experience.
When my husband and I decided to
embark on this incredible journey, we
understood that we would face many
uncertainties. It was therefore very
important for us to be surrounded by
positive energy and enthusiasm. Our
amazing group of doctors guided us
through the entire pregnancy and
monitored my progress closely.
My first trimester was fairly unevent-
ful. I was very lucky not to experience
morning sickness, but did feel
extreme exhaustion. I continued
receiving transfusions every other
week and my haemoglobin remained
constant in the 10s. Given the amount
of research available on the effects of
Desferal on the foetus, I made the
decision to discontinue it for as long
as possible. My ferritin was 1,200
when I first became pregnant and
slowly dropped throughout the first
three months. As with any pregnancy,
a lot of stress is placed on the heart
due to the increased amount of fluids
March 2006 / 35
in the body. Therefore it was impor-
tant to monitor the effects on my
heart. Prior to the pregnancy, my ejec-
tion fraction (EF) was 68% and
dropped slightly to 58% by week 16.
Although it was still within normal
range, I had an echo done once a
month for the rest of the pregnancy.
By the second trimester, my energy
returned and I continued working full-
time. My ferritin continued to drop
and my EF remained at 58% so I still
did not restart my desferal. I truly felt
wonderful and remained positive.
Things shifted slightly in my third
trimester. My ferritin was still drop-
ping, however my EF also dropped, to
48%. At 26 weeks it had dropped to
42%. At this point, my cardiologist put
me on 'therapeutic' bed rest: that
meant staying off my feet as much as
possible and limiting my outings. I
began working from home and was
pampered by family and friends.
Fortunately, as the baby continued to
develop normally, my obstetrician
reminded me of the importance of
getting back on Desferal and assured
me that the baby would not be affect-
ed. At about 28 weeks, my haemoglo-
bin had dropped into the low 9s, so
began weekly one-unit transfusions.
My cardiologist and haematologist felt
that with the increased amount of flu-
ids, the last few weeks of pregnancy
would put even more stress on my
heart. I wanted to try natural labour
and was given the go-ahead. After
confirming with my OB that the baby
would be ok, we decided that I should
be induced at 38 weeks. After a full
day experiencing all the phases of
labour, I reached a point where I
stopped progressing. We all agreed it
was best to go with a Caesarean and
alleviate any additional stress that
hard labour would bring.
I spent the next couple of weeks recu-
perating and learning the new won-
ders of motherhood. I'm being trans-
fused every other week again and my
haemoglobin has been around 11
each time. Best of all, my baby weight
has vanished! It seems motherhood
agrees with me!
This past year has been a whirlwind
and the experience of a lifetime. I
hope all women living with thalas-
saemia will be inspired by my story
and realise that it is important to
believe in your dreams.
This article first appeared in TAG Newsletter
36 / March 2006
Prague, Czech Republic
7th-8th March 2006
International
Plasma Protein
Congress
(IPPC) 2006
T he Plasma Protein Therapeutics
Association (PPTA) held its annual
International Plasma Protein Congress
(IPPC) on 7th–8th March 2006, at the
Marriott Hotel in Prague, capital of the
Czech Republic.
The PPTA is the primary advocate for
the world’s leading producers of plas-
ma-based and recombinant biological
therapeutics. The medicines produced
by PPTA members are used in treating
life-threatening diseases and serious
medical conditions, including bleeding
disorders, immune system deficien-
cies, burns and shock.
The IPPC has rapidly established itself
as the leading international congress
in the field of plasma protein therapies.
IPPC 2006 featured internationally
renowned speakers, offering perspec-
tives on key issues affecting plasma
protein therapeutics, as well as
updates on current and future devel-
opments in the industry.
Day One
Delegates split into parallel tracks,
each comprising two sessions, allow-
ing participants to focus on areas of
particular interest. Session one
addressed issues relating to access to
and choice of plasma protein thera-
pies, while session two focused on
reimbursement policies and trends.
Sessions three and four assessed,
respectively, the regulatory environ-
ment in an enlarged European Union,
and global issues affecting the collec-
tion of plasma for fractionation.
Day Two
Participants came together to hear
presentations on the market for plas-
ma protein therapies, updates on
international regulatory systems, and
reviews of product and clinical devel-
opments.
For more on IPPC2006, visit
www.ippc2006.com
Source: Johan Prevot/PPTA Europe
By Dr Mahmoud
Hadipour Dehshal,
Chairman
News from the
Iranian Thalas-
saemia Society
T he Iranian Thalassaemia Society,
founded in 1989, is an extremely
active organisation, working to sup-
port thalassaemia patients and parents
in Iran in a range of ways.
Here is an overview of some our most
important recent achievements:
ñ Secured the introduction of a pro-
gramme of subsidies and reduced
costs for thalassaemia patients, fol-
lowing regular meetings with Iran's
Minister and Deputy Minister of
Welfare and Social Security.
ñ Collection of demographic infor-
mation and data on patients with
thalassaemia, helping to clarify the
status of the disease in the country.
When we began this programme,
estimates of the number of patients
in Iran ranged from 15,000 to
35,000. According to data collected
by the Iranian Thalassaemia
Society, there are currently 18,649
registered patients in Iran. Such
information is crucial in the design
of treatment and prevention pro-
grammes. However, further work
is needed, including establishing a
patients’ information network.
ñ The Society has also worked to
establish clear criteria regarding
payment and support given to
patients, including allocating finan-
cial support on the basis of treat-
ment cost. This, along with adjust-
ments to Society staffing, has
helped the organisation clear all
debts to become a financially viable
entity.
ñ Building strong links with govern-
mental bodies involved in the med-
ical care of thalassaemia patients is
an important part of our work. We
have forged strong links with the
Iran's main blood transfusion
organisation, as well as with insur-
ance companies. A series of joint
projects has included publicising
the need for continuous blood
donation and establishing co-ordi-
nated programmes for the distribu-
tion of medical supplies to patients.

The Society is also working with
the blood transfusion organisation
to ensure the provision of safe
blood for thalassaemia patients,
from multiple known donors. The
Society actively advocates the need
for safe, quality blood for thalas-
saemia patients in Iran.
ñ Educational workshops are a key
way of keeping patients and par-
ents informed of various aspects
relating to thalassaemia. The
Society has organised workshops
in a number of provinces across
the country - in Tabriz,
Kermanshah, Guillan and Karaj.
ñ Regular newsletters are another
way of keeping patients, parents
and medical practitioners informed
and in touch. After a period in
which Society newsletters were
published irregularly and without
reference to national laws govern-
ing the publication of internal bul-
letins, the Society has focused on
producing its newsletter regularly
and according to legal require-ments.
ñ Having access to support locally
makes a huge difference to thalas-
saemia patients. The Society has
F ighting for their rights - and work-
ing for what they need - is some-
thing thalassaemia patients are all too
familiar with.
What's the upside?
As the Thalassaemia Welfare Centre in
Chittagong, Bangladesh is determined to
show, with hard work and determina-
tion, they get what they need.
The Centre has launched an ambitious
fundraising programme, aimed at secur-
ing sufficient resources to open a hospi-
tal for the treatment of patients with tha-
lassaemia.
The campaign kicked off on 18
therefore established independent November 2005, under the slogan ‘We
branches in each of the country’s
vow to make a thalassaemia hospital
provinces, offering easier access to
ourselves’.
patients and parents. The Society
The fundraising effort has been named
has also drawn up a new constitu-
tion, giving all provincial branches
the right to vote at the Society
assembly. Votes are weighted
according to the number of
patients registered at each branch.
ñ The Society also organises recre-
ational tours and welfare pro-
grammes for patients, including
recreational camps held in
Namakabroud, Tangevashi and
Tochall.
ñ Last but certainly not least, the
Society is an active participant in a
survey aimed at identifying possi-
ble weaknesses in Iran's new
National Thalassaemia Prevention
Programme.
Chittagong, Bangladesh
18th November 2005
‘Doing it
ourselves’
By Ashis Dhar,
General Secretary
March 2006 / 37
 the Earthen Bank Project - a reference to
the creative way in which funds will be
collected.
Every member of the Thalassaemia
Welfare Centre has been given a clay
(earthen) piggy bank, which they will
endeavour to fill over the course of the
next year. One year down the line, all the
piggy banks will be returned to the
Centre... and the exciting process of tot-
ting up the total will begin. Good luck
and well done!

10th International Conference on Thalassaemia and Haemoglobinopathies &

12th International TIF Thalassaemia Conference for Patients and Parents
(contd from page 3)

40 / March 2006