An educational leaflet by the Thalassaemia International Federation (TIF) with important information for β-thalassaemia patients on hematopoietic stem cell transplantation (HSCT), more commonly known as bone marrow transplantation (BMT).
An educational leaflet aiming to strengthen the knowledge and understanding of patients with thalassaemia and other haemoglobin disorders across the world on most aspects relevant to gene therapy.
Anemia in Chronic Kidney disease is a fascinating area of study both for the Basic scientist and Practising Nephrologist . In this talk , both areas are highlighted with emphasis on erythropoietin .
An educational leaflet aiming to strengthen the knowledge and understanding of patients with thalassaemia and other haemoglobin disorders across the world on most aspects relevant to gene therapy.
Anemia in Chronic Kidney disease is a fascinating area of study both for the Basic scientist and Practising Nephrologist . In this talk , both areas are highlighted with emphasis on erythropoietin .
Cardiovascular disease is the leading killer for both men and women among all racial and ethnic groups in the world wide. According to the Centers for Disease Control (CDC) studies among coronary heart disease (CAD) patients, 90% of patients have had prior exposure to at least one heart disease risk factor that contributed to their disease
Uctioleuco Reduction of Blood Products- A Rising Essentiality in Transfusion ...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Thalassemia Care and Research
Elliott Vichinsky, M.D.
January 18, 2014
Thalassemia Patient and Family Conference
Northern California Comprehensive Thalassemia Center
Children's Hospital Oakland
Global distribution and description of the thalassemia disorders, treatment and complications.
Cardiovascular disease is the leading killer for both men and women among all racial and ethnic groups in the world wide. According to the Centers for Disease Control (CDC) studies among coronary heart disease (CAD) patients, 90% of patients have had prior exposure to at least one heart disease risk factor that contributed to their disease
Uctioleuco Reduction of Blood Products- A Rising Essentiality in Transfusion ...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Thalassemia Care and Research
Elliott Vichinsky, M.D.
January 18, 2014
Thalassemia Patient and Family Conference
Northern California Comprehensive Thalassemia Center
Children's Hospital Oakland
Global distribution and description of the thalassemia disorders, treatment and complications.
The “Thalassaemia from A to Z” electronic glossary is a comprehensive, easy-to-use, educational tool for thalassaemia, including definitions of all important concepts on the prevention, management, treatment, organ complications, and plenty of other aspects related to the disease.
- English -
Dr. Mohamed B. Aswad is an oncologist in Deming, New Mexico and is affiliated with Mimbres Memorial Hospital. He received his medical degree from University of Aleppo Faculty of Medicine and has been in practice for more than 20 years.
Insights and Hopes in Umbilical Cord Blood Stem Cell TransplantationsAnkita-rastogi
Umbilical cord stem cell preservation makes an ideal choice for parents who are concerned for their child’s life in long run. Why take any chance if you have an opportunity to preserve the stem cells of your child, right at the time of birth which can later be used for various transplantation at the time of need. For more info: http://www.cryobanksindia.com/
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Reversal of warfarin associated coagulopathy prothrombin complex concentratesTÀI LIỆU NGÀNH MAY
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Despite the advances in diagnostic methods and techniques for surgical treatment in the last two decades, aortic diseases remain a major cause of mortality and cardiovascular morbidity, challenging physicians and molecular biologists. It is believed that about 600 million years ago, during the Cambrian period, variant forms of life appeared, among them were the oxygen-producing cyano bacteria.
HCT and Gene Therapy for Thalassemia Major
Mark Walters, M.D.
January 18, 2014
Thalassemia Patient and Family Conference
Northern California Comprehensive Thalassemia Center
Children's Hospital Oakland
Provision of ideal transfusion support – The essence of thalassemia careApollo Hospitals
Thalassemia major is a major cause of transfusion dependence among patients world over. Provision of an adequate, uninterrupted and safe blood supply for these patients is the responsibility of the blood services as well as the society as a whole. Thalassemia management has evolved over a period of time and so have transfusion services. Various technological advancements have been introduced in the last few decades in order to enhance blood safety. Adoption of these newer technologies coupled with increasing awareness about voluntary blood donation in the general population can go a long way in improving the life expectancy as well the quality of life in these children.
Similar to Bone Marrow Transplantation (BMS) in β-Thalassaemia (2018) (20)
By providing a short pocket guide describing the best possible practices in the treatment and management of transfusion-dependent thalassaemia (TDT), TIF seeks to support physicians worldwide in making good clinical decisions that can benefit individual patients with the disorder and enable them to advocate for more and better resources for thalassaemia care at the level of national health authorities.
The 4th edition of the original full-length Guidelines, published in June 2022, includes a full review of the evidence supporting almost each recommendation for physicians to know all the facts that form the basis of their clinical decisions in the form of a long textbook, difficult to use on a daily basis.
The ‘Basic Recommendations in Brief for Treating Physicians’, based on and complementing the ‘Guidelines for the Management of Transfusion Dependent Thalassaemia (4th Edition – 2021)’, is an easy-to-understand, user-friendly resource for thalassaemia-treating clinicians, especially for those who are not fully experienced and well-knowledgeable of the management of patients with this serious chronic disorder, or those operating in Urgent and Emergency Care (UEC) settings admitting haemoglobinopathy patients.
These key recommendations offer valuable guidance on a variety of thematics pertaining to thalassaemia management, ranging from blood transfusion and iron overload and chelation to the assessment of cardiovascular and liver disease, pregnancy management, and much more.
Here's exactly where we're at with vaccines and #reatments for COVID-19!
In this newly published issue of TIF's ''COVID-19 Vaccinations & Therapeutic Drugs'' Guide, you can find out the latest on the current status of COVID-19 vaccinations across the world, the new vaccines and promising treatments, such as molnupiravir, and much more.
TIF, its Board of Directors, and its International Scientific Advisory Board proudly present the 4th Edition of the Federation’s most prestigious and renowned publication, the TIF Guidelines For The Management of Transfusion-Dependent Thalassaemia (TDT).
Since 1999, when the very first edition was originally released as part of the Federation’s Educational Programme, the TIF Guidelines have been adopted and used extensively by academics, researchers and healthcare professionals all over the world as the only evidence-based reference text concerning the treatment of patients with TDT.
The newly launched edition includes brand new chapters on the recently approved modalities of patient treatment, the value of patient engagement at the decision-making level, the Reference Centres’ contribution to patient care, and much more.
Nurses play a critical role in any team of healthcare professionals involved in the care of patients with chronic diseases, including Hb disorders such as thalassaemia
and sickle dell disease. These are extremely challenging diseases that are fatal if left untreated.
However, by sharing expert knowledge on their prevention and treatment, these conditions can be effectively managed.
TIF places great importance on nursing as a valued part of patient care well beyond the medical component. We hope that this Guide will help and motivate more nurses across
the world to become involved in the care of patients with this group of diseases.
The Global Thalassaemia Review 2021 (GTR) constitutes perhaps the most comprehensive work of the last decade on thalassaemia.
Comprising of almost 500 pages, the real face of thalassaemia will be revealed to the reader demonstrating the immense disease burden that falls on the shoulders of thousands of thalassaemia patients and their families in their struggle to access quality healthcare services that will enable their survival.
In these updated guidelines, we feature the most prominent pathophysiologic mechanisms and clinical morbidities commonly encountered in NTDT patients, and provide
practical recommendations for combating these morbidities.
Our recommendations stem from the most recent evidence delivered through published observational studies or clinical trials.
In areas where evidence is unavailable or insufficient, the editors provide, through consensus, management recommendations using their clinical expertise in treating NTDT patients.
This booklet on the prevention and diagnosis of the haemoglobinopathies is intended to be a reference
booklet serving as a short guide directed towards health professionals and laboratory scientists undertaking haematological screening and molecular diagnosis of the thalassaemias and other haemoglobin disorders.
By providing a short pocket guide describing
the best possible practices in the treatment and management
of Transfusion Dependent Thalassaemia (TDT), TIF seeks to support physicians worldwide in making
good clinical decisions that can benefit individual patients and
enable them to advocate for more and better resources for
thalassaemia care at the level of national health authorities.
This effort is also supported in TIF’s educational programme,
aiming to ensure that physicians and other healthcare
professionals have all the necessary knowledge to support
their patients.
More from Thalassaemia International Federation (9)
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
2. THALASSAEMIA
INTERNATIONAL
FEDERATION
- 2- - 3-
This leaflet contains important information for β-thalassaemia patients on
hematopoietic stem cell transplantation (HSCT), more commonly known as bone
marrow transplantation (BMT), a term to be used throughout this leaflet. Patients
and families can use this leaflet as a guide for further relevant discussions with
their treating physicians.
The content of this educational leaflet (Number 1 in the series), has been
adapted from the electronic educational platform of TIF
, - TIF’s Thal e-Course1
for patients and parents - with the support of members of TIF’s advisory medical
and scientific panel. It has been reviewed and edited by thalassaemia patients
from TIF’s expert patient advisory panel and Professor Pietro Sodani2, who has
provided the data included herein.
Disease definition
β-thalassaemia or thalassaemia major is a genetic disorder of the blood caused
by the inheritance3
of a defective (or mutated) β-globin gene As a result the
body can only produce little or no normal adult haemoglobin (Hb), the substance
inside the red blood cells (RBCs) that, on account of the iron that it contains, is
responsible for carrying oxygen throughout the body to support normal bodily
function and maintain human life.
The Pathophysiology of β-Thalassaemia
β-thalassaemia is caused by reduced or absent synthesis of the beta-globin
chains of the adult haemoglobin (HbA) tetramer, which is made up of two
alpha- and two beta-globin chains (α2β2). When beta-globin chains (β) are
absent, alpha-globin chains (α) and their degradation or break down products
precipitate (deposited in an insoluble form), causing ineffective erythropoiesis4
and haemolysis, which lead to severe anaemia. In turn, anaemia stimulates
erythropoietin synthesis, resulting in intense proliferation5
of the bone marrow,
skeletal deformities, and a variety of growth and metabolic abnormalities.
The patient can only survive through extensive multidisciplinary support
including mainly lifelong blood transfusions of donated Red Blood Cells (RBCs),
containing healthy Hb. Furthermore, as transfused RBCs complete their lifecycle
in the blood and break down (a normal biological process of the body), they
release Hb and the iron contained in it. Thus, these patients need lifelong iron
chelation therapy to treat (remove) this excess and toxic iron which causes, if left
unaddressed, severe damage to vital organs of the body.
Bone Marrow Transplantation in β-thalassaemia
An educational leaflet for the patient
1
The Thal e-Course is offered and created by the Thalassaemia International Federation (TIF) free of
charge, following registration at http://academy.thalassaemia.org.cy/.
2
Dr Pietro Sodani, Cure Thalassaemia co-founder & Scientific coordinator.
3
When both parents are carriers of the thalassaemia trait, they have 25% chance in every pregnancy of
having a child with thalassaemia, an inheritance mode referred to in science as autosomal recessive
Mendelian inheritance. To avoid having an affected child, couples can get tested or screened to
investigate whether they are carriers of thalassaemia trait before they decide to have a family.
4
Erythropoies is production of red blood cells; ineffective erythropoiesis indicates that despite active
erythropoiesis there is a lack of effective production of mature red cells.
5
Bone marrow cells divide repeatedly, producing large numbers of red cell precursors.
Bone Marrow & Stem Cells
3. THALASSAEMIA
INTERNATIONAL
FEDERATION
- 4- - 5-
Thalassaemia major is described as a multi-organ disease (i.e. one in which
many organs of the body may be affected) with many and complex national,
public health and social repercussions and, as such, addressing effectively
its management requires well structured, multidisciplinary approaches in the
context of national programmes within the healthcare systems.
The patient as described previously suffers from severe anaemia and can only
survive through lifelong blood transfusions of donated RBCs, containing healthy
normal haemoglobin (Hb). As transfused RBCs finish their lifecycle in the blood,
they break down releasing their Hb and the iron which is contained in it. Iron is
the element that is responsible for binding oxygen and transferring it from the
lungs through the blood across the body. Thus, in addition to blood transfusions,
thalassaemia patients essentially need another treatment intervention referred
to as iron chelation therapy in order to treat (remove) this excess iron which is
very toxic. The iron, if left in the body, will cause serious damage to vital organs
such as the heart, liver and endocrine systems leading to many and serious
medical complications and early death.
In low- and middle-income countries sadly, a big number of children with
β-thalassemia die each year due to the lack of adequate and/or safe blood
transfusion treatment and suboptimal or no chelation therapy. Furthermore,
the aging of this population leads to increasing development of new chronic
complications, such as heart disease, liver disease, and endocrine disorders,
leading to additional morbidity and premature mortality
To date, the only available approach that has been used for decades now to cure
β-thalassaemia is allogeneic bone marrow transplantation (BMT) or allogeneic
haematopoietic stem cell transplantation (HSCT)6
although considerable and
intensive genetic-based research has given in more recent years the global
healthcare professional and the patient communities immense optimism and
hope of having in the near or very near future another totally curative approach.
For the purposes of this leaflet, references will only be made to the bone
marrow transplantation approach.
More than 30 years have passed, since the first allogeneic haemopoietic stem
cell transplantations (HSCT) were performed in patients with thalassaemia.
After pioneering experiences in the 80s and early 90s, allogeneic transplantation
remains the only widely available curative option for thalassemia major. In recent
years, the indications for HSCT have been expanded, and it is now increasingly
applied worldwide.
Survival rates for 1493 Bone Marrow transplant in Thalassemia
During the Period 2000-2014
Adapted from Baronciani D, Angelucci E, Potschger U, et al. Hematopoietic stem cell transplantation
in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation
Hemoglobinopathy Registry, 2000–2010. Bone Marrow Transplant. 2016;51(4):536-541.
HSCT is more popularly known as BMT since the BM is the main source
of stem cells of transplantation. Bone marrow transplantation (BMT) is a
medical procedure during which stem cells (a special young form of blood
cells) are transferred from a healthy individual (i.e., the donor) into the
blood-producing tissue in the bone marrow of the individual who has a
blood disease such as β-thalassaemia (i.e., the recipient).
Stem cells are starter cells which like almost all other parts of the blood, are
produced in the marrow, that is, the soft blood-forming tissue within some
large bones of the human body. Stem cells progressively develop into highly
specialised cells. Red blood cells (RBCs) are one type of such highly specialised
cell. These contain Hb, develop from the maturation of stem cells and have the
specialised ability to carry oxygen across the body organs and tissues which is
required for their growth and development.
About Thalassaemia, Treatment and Cure
6
BMT is also referred to as allogeneic HSCT because it uses stem cells from an “allo” (Greek for “other”)
donor. Gene therapy, on the other hand, a currently experimental approach to thalassaemia cure, uses
stem cells from the patient him/herself (“auto” Greek for “self”) and is thus called autologous HSCT.
Bone Marrow Transplantation … all about it.
4. THALASSAEMIA
INTERNATIONAL
FEDERATION
- 6- - 7-
Bone marrow transplantation (BMT) is to date the only well-established curative
treatment for thalassaemia and shows excellent long-term results.
Outcomes, however, depend on the patient’s pretransplant, clinical condition
and the expertise of the centre performing the BMT procedure.
Classification of risks
A risk stratification system based on (1) hepatomegaly (i.e. large liver) greater
than 2 cm, (2) liver fibrosis (liver cell damage), and (3) irregular chelation history
categorizes patients with thalassaemia into 3 risk groups:
1. Class 1, with none of these factors;
2. Class 2 including 1 or 2 of these factors; and
3. Class 3 with all the 3 above factors.
Transplantation outcome worsens with increasing risk category, with the best
outcomes achieved in risk Class 1 or 2 (as described above) and in patients
transplanted with an HLA-fully-matched sibling donor. Modified protocols
however developed in more recent years have the potential to make allogeneic
BMT accessible to all class 3 younger patients with results equal or near to
equal to those of class 1 or class 2 patients with thalassemia.
Patient-related: Iron overload limits the patient’s chances of a successful BMT
as it causes damage to vital organs of the body such as the liver. Ideally, the
patient candidate for BMT should: (1) be 16 years old or younger; (2) have a
More about Bone Marrow Transplantation
Requirements for a successful Bone Marrow Transplant
Stem cells can be taken from (1) the donor’s bone marrow (bone marrow
donation); (2) the donor’s bloodstream (peripheral donation); or (3) a
newborn baby through the umbilical cord (cord blood donation). Bone
marrow is usually the best source of red cells as it can provide a larger
quantity of stem cells than peripheral or cord blood. If successful, BMT can
offer a complete and permanent cure to β-thalassaemia patients, including
no need for blood transfusions.
Important note: BMT only treats the bone marrow and not the whole
genome of the patient (the sum of his/her genes). In other words,
transplanted patients might become free of the need to receive treatment
for thalassaemia, but they will still carry the defective thalassaemia gene
i.e., the one that causes thalassaemia and can therefore still pass it on to
their children.
In addition, cytotoxic drugs (chemotherapy), which are used as part of the
BMT procedure to suppress the activity of the patient’s own bone marrow
and make room for the donor’s stem cells, can reduce fertility, in both
males and females, or even eliminate the possibility of future pregnancy
for transplanted patients.
5. THALASSAEMIA
INTERNATIONAL
FEDERATION
- 8- - 9-
healthy liver and (3) have low body iron content (minimal excess iron). Older
patients with pre-existing conditions run more risks of developing complications
following BMT, even when having HLA fully-matched sibling donor.
The donor
Donor-related: For a successful transplantation i.e., with minimal or absent
unwanted reactions, the donor’s stem cells must have identical or nearly the
same HLA7
characteristics as the stem cells of the recipient. Only siblings
(brothers or sisters of the patient) can have exactly or almost exactly the same
HLA characteristics and therefore be fully-matched donors to the patient. BMT
can also be performed with less compatible (matched) donors, which can be
HLA-matched but unrelated (non-family) donors, or parent donors (known as
haploidentical donors). In these cases, the chances of a successful BMT are
considerably reduced and the patient is thus at increased risk of developing
complications after the transplant.
The doctor must carefully assess the risks and benefits of transplantation
according to the clinical condition of each individual patient and the expertise
of the transplantation centre. The doctor must then fully share all the risks
and benefits with the patient (or parents if the patient is very young) in order
to allow the patient (or parents) to make a fully informed choice about going
ahead with the transplant.
Donor compatibility and transplantation success rates
To check HLA compatibility, blood or, more recently, saliva is used to compare
the cells of the donor with those of the patient.
Fully matched sibling donors: Siblings, i.e., the brothers and sisters, are more
likely to share the same HLA characteristics and are therefore the best donors of
bone marrow for a patient. However, less than 30% of the patients are able to find
a fully-matched sibling stem cell donor. The chances may decrease or increase
depending on the size of the family. The chances increase also in societies with
high prevalence of customary cousin marriage (consanguinity).
7
HLA characteristics or Human Leukocyte Antigens are proteins found on the surface of almost all the
cells of the body. They are used by the immune system to recognize and thus not attack the individual’s
own cells, and to differentiate them from foreign cells such as bacteria.
Reports from experienced centres suggest that chances of overall survival from BMT
with fully-matched sibling donor are over 90% whilst disease free survival is over 80%.
Reference: Lucarelli et al. (2012)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331690/
Matched unrelated donors: It is, of course, possible for recipients to find a
suitable donor in the general population, by searching in international database
platforms of volunteer donors, such as the Matched Unrelated Donors (MUDs)
platforms. However, the difficulties of trying to find a match from unrelated (non-
family) donors are considerably greater, while, on the other hand, the existence
of even very small differences between the donor and the recipient can cause
unwanted reactions, thus increasing the risks for the patient. More recent data
strongly suggest that improvements in donor selection and transplantation
preparation have improved the safety of unrelated donor BMT for thalassemia
treatment. This appears to be a viable treatment option for selected patients
when there is no suitable sibling donor.
Haploidentical donor: Haematopoietic cell transplantation (HCT) from an
HLA-matched related or unrelated donor remains the only curative therapy
for haemoglobinopathies to date. However, less than 30% of patients have an
HLA-matched sibling donor, and in a recent study from the US National Marrow
Donor Program, <52% of non-Europeans found a matched unrelated donor.
Furthermore, the lack of donor registries and cost of recruiting unrelated
donors makes this approach unaffordable for developing countries, where
many patients with haemoglobinopathies reside.
A haploidentical related donor is often available and represents an alternate
source of stem cells.
More specifically, the mother or father of the patient can become stem cell
donors for their child and they are referred to as haploidentical donors
because they only have 50% HLA match with the patient child. The 50%
mismatch, however, can cause severe and dangerous complications to
patients after the transplant. Research is ongoing and already some protocols
have been developed by experts in the field aiming to reduce the severity
of these adverse reactions, and increase the chances of patients using a
parent’s stem cells with lesser or, if possible, no side effects.
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Compatibility testing
Once the initial blood tests have shown that the donor and recipient’s
HLA are compatible, the doctors perform a test in the laboratory, known
as cross-matching, to make sure that no reaction is produced when
the donor’s cells are added to the recipient’s blood. If no reaction is
produced, the transplantation procedure can proceed. In very rare
cases, the recipient’s blood might reject the blood of HLA-compatible
donors during the cross-matching test, in which case the doctor decides
not to continue the transplantation procedure.
Stem Cell Donation
Stem cells are usually harvested from the pelvic bone (iliac crest) of the
healthy donor (bone marrow donation). Nonetheless, stem cells can
also be drawn from the donor’s bloodstream directly using a needle
(peripheral donation), which is the least invasive technique currently
available. In special occasions, and if specialised staff and procedures
are available, stem cells are harvested from cord blood through the
umbilical cord of a newborn baby, in which case the quantity of stem
cells obtained may present challenges to the success of the transplant.
Myeloablation
This procedure prepares (or conditions) the patient to receive the
donor’s stem cells. Before the transplant takes place, the patient
undergoes a period of treatment that destroys the patient’s own bone
marrow cells in order to make room for and create the environment to
host the donor’s cells, a process known as myeloablation. This process
is carried out using mainly chemotherapy (drugs that destroy bone
marrow cells) or sometimes irradiation (this is no longer recommended
in non-malignant disorders such as thalassaemia).
Transplantation
The donor’s stem cells are transfused into the recipient’s bloodstream
in a similar way to a regular blood transfusion. Once in the recipient’s
blood, the donor’s stem cells travel to find their way to the bone marrow,
which is located in the large bones of the body, and start producing
normal, healthy blood cells, including red cells. This process takes
about 2-3 weeks.
Cure
If the transplantation is successful, the healthy donor’s stem cells, with
a normal β-globin gene, take over the recipient’s bone marrow activity
and continue to produce healthy red cells for the rest of patient’s life.
This means that the patient is cured of β-thalassaemia.
Bone Marrow Transplantation procedure
8
The ideal patient is: (1) 16 years old or younger; (2) has a healthy liver; (3) has no or little iron overload.
Overall Survival and Thalassaemia-Free Survival Rates Are
Highest in Thalassaemia Patients With a Matched Sibling Donor
Donor Type Overall Thalassaemia-Free
Survival Rate(%)* Survival Rate(%)*
(2 years post-ΒΜΤ) (2 years post-ΒΜΤ)
Matched Sibling Donor (n=1061) 91 ± 0.01 83 ± 0.01
Matched Related Donor (n=127) 88 ± 0.04 78 ± 0.05
Mismatched (n=57) 68 ± 0.11 68 ± 0.11
Unrelated Donor (n=210) 77 ± 0.03 77 ± 0.03
NB: The success rate and outcomes of BMT always depend on the experience of the centres,
the condition8
of the patient before the transplant, as well as other factors.
Therefore, the results are not the same for every centre even within the same country.
The above percentages indicating the success rate of BMT procedures used to treat
β-thalassaemia are taken from research performed, mainly in Europe in well experienced
centres, albeit through the years a number of expert centres with very successful outcomes
published in the literature have developed in other regions of the world.
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• Infections and bleeding: They are caused during the process of
myeloablation, because of the toxic effects of chemotherapy or irradiation.
Considerable research is ongoing to use “milder” chemotherapy treatment
to reduce to the maximum possible level the myeloablation treatment-
related side effects.
• Graft versus Host Disease (GvHD): The donated stem cells attack the
patient’s own cells because they consider them as foreign. GvHD can be
acute (which is often lethal) or chronic, and severely affects the patient’s
quality of life.
• Graft rejection: The patient’s body rejects and attacks the donated cells.
The chances of GvHD or graft rejection are increased when the donors are
not fully HLA-matched sibling donors. To prevent GvHD and graft rejection,
patients need to take medication (immunosuppression) for a long time
after the transplantation to keep suppressing their immune system and
prevent their body from reacting to or completely rejecting the donated
cells. However, immunosuppression is not always successful in doing so,
and transplanted patients may also in addition develop other unwanted
effects (due to immunosuppression) e.g., infections.
• Inadequate dose of stem cells from the donor (usually when stem cells
are harvested through the umbilical cord): This may lead to either failure
of the transplant or the production of a mixed population of red cells, some
from the donor and some red cells that are still thalassaemic (this is called
a chimera).
• Reduced fertility: Occurs as a result of the myeloablation process that
takes place before the transplantation, during which chemotherapy is
used to completely or partially destroy the patient’s bone marrow. The
chemotherapy medications are very toxic and can damage the function
of the gonads i.e., the testes in males and the ovaries in females. Male
sperm and female ova (eggs) may be destroyed either temporarily or
permanently. Factors that affect fertility are also: (1) the age of the patient at
the time of the transplantation (children below the age of 12 have a greater
chance of infertility), and (2) the conditioning regimen (i.e. the drugs used
in myeloablation).
FERTILITY... more information
According to existing data, approximately 40% of transplanted patients (males
and females) may enter or pass through puberty9
normally, despite the fact
that most of them may present clinical evidence of gonadal dysfunction10
; that
is, low levels of testosterone in males and oestrogen in females. This means
that both transplanted males and females may show signs of normal puberty,
including the development of secondary sexual characteristics such as adult
breasts, testicles, facial hair; and female menstruation. In some patients with
thalassaemia, the insufficient levels of gonadotropin11
which is responsible for
the absence of pubertal development is probably caused by the iron overload
that patients suffered before they had bone marrow transplantation - particularly
seen in older patients. This is added to the effect of chemotherapy on gonadal
development.
Most affected group: Females who have passed through puberty, experiencing
menstruation (post-menarcheal females), seem to be an extremely sensitive
group to the harmful effects of the transplantation process since nearly 100% of
themarereportedtoexhibitsecondaryamenorrhea(i.e.absenceofmenstruation)
and elevated gonadotropin levels after BMT. For those transplanted below the
age of 12, pregnancies are rare.
Overall, there are limited data available in the literature about the late effects
of BMT on the pubertal development and future fertility, which calls for more
research into this field.
However, fertility constitutes one of the very important issues that need to
be thoroughly discussed between the treating doctors and the patients very
early in time and before any decisions are made or channeled.
Risks and adverse events associated
with Bone Marrow Transplantation
9
Puberty is the period during which adolescents reach sexual maturity and become capable of
reproduction. Girls experience puberty between the ages of 8 and 13, while boys experience puberty
between the ages of 10 and 15. Some individuals may go through puberty earlier or later. During this
time, the body undergoes various changes (e.g., development of secondary sexual characteristics such
as adult breasts, testicles, facial hair and female menstruation).
10
Gonadal dysfunction is the damage to the function of the gonads; that is, the testes in males and ovaries
in females. The gonads are responsible for producing the hormones that assist in the development of
the reproductive organs of the individual and the promotion of secondary sexual characteristics.
11
Gonadotropin is the hormone that is produced by the pituitary gland and which stimulates the ovaries
or the testes.
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After the BMT, the transplanted patient needs to:
• Have careful and expert follow up by haematologists (and according
to international protocols) since GvHD may appear after the patient is
discharged from the hospital (which is a major cause of death in patients
particularly living in developing countries).
• Continue iron chelation treatment to dispose of the toxic iron that was
accumulated in their body before the transplant. Iron chelation can be done
by removing blood through phlebotomy (venipuncture) or through iron
chelation regimens, depending on the level of ferritin in the patient’s blood.
The treating physician assesses the patient and decides which option is
best for him or her.
• Continue to have comprehensive and reliable organ monitoring (according
to international guidelines) to prevent disease complications. For example,
heart or endocrine disease that developed before BMT should still be
treated adequately after the transplantation.
In any case, the patient should continue to be very carefully monitored
throughout his/her lifetime.
Post-BMT Treatment
Recommendations
1. Transplanted patients planning a pregnancy should remember that their
genes remain affected by β-thalassaemia, and therefore, the disease can
still be passed on to their children.
2. Patients are advised to discuss all options and concerns they have about
fertility and the potential negative effects of BMT with their treating physician
before the initiation of the procedure.
3. Patients at puberty and older patients, as well as their families, should
know about the fertility risks involved in BMT well before the transplant
in order to make an informed decision whether to go ahead with the
transplant or not.
4. Patients at puberty and older patients (as well as their families) should be
fully informed by their treating physicians about currently available fertility
preservation options prior to the initiation of BMT therapy.
Fertility preservation options may include saving sperm or ova in deep
freeze before the transplant for later use. There are also other fertility
preservation options for both female and male patients prior to or at
puberty. These options are still considered experimental but patients
should nevertheless discuss them with their treating physicians.
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5 FAQs written by Dr. Pietro Sodani, Cure Thalassemia co-founder & Scientific
coordinator Bone Marrow Transplantation (BMT) for Thalassemia (Sodani, 2019))
http://www.curethalassemia.org/faq
General questions
Is there a cure for thalassaemia major?
Yes, to date and until new curative methods (which are on the way)
are fully and officially licensed (authorized) by the European Medicines
Agency (EMA) and the Food and Drug Administration (FDA), bone
marrow transplantation (BMT) is the only method of definitive cure for
thalassaemia, which when successful can result in no more need of
blood transfusions (thalassaemia free).
My child has beta thalassaemia major, can he be cured?
Your child may be cured (no more transfusions) with bone marrow
transplant (BMT). The best potential donors for a BMT are brothers and
sisters and the BMT experts need to know their age and review, with the
involvement of treating specialists, their clinical status before initiation of
discussions and any planning.
My baby doesn’t have a matching sibling. What can we do to use BMT
and cure him/her from thalassaemia?
These are other options that you have:
a) you can find a donor in a bone marrow donor bank. It usually takes time
(3-6 months) and has a cost. There are centres and experts that can help
you to seek for the donor
b) sometimes the mother is a compatible donor
c) even if the mother is not fully compatible, she can be used as donor
For options b) and c), we suggest for both parents (sometimes the father
can be used as donor) take a simple blood test called HLA typing to see
how it matches the patient’s HLA.
I’ve given you all the information about my son, who has thalassaemia
major. Do you suggest doing the BMT?
From an ethical point of view we can’t tell you what to do. The decision
is yours (parents) and in cases of adults, of the patient himself/herself,
after receiving and understanding all relevant information regarding
the whole process from a RELIABLE SOURCE. The role of the medical
community is to provide you (or your parents) with all the facts and the
risks, as documented in international published literature, but the final
decision must be taken by you (or your parents) taking into consideration
all parameters including the country you (or the parents) live in, the health
care system, the cost, the experience of the Centre and the risk/ benefit,
based on your (or your child’s) age, clinical state and the quality of care
you (or your child) has been receiving throughout your life.
Why should I choose BMT to cure my thalassaemia?
BMT medical experts say that there are many good reasons. Read
them on relevant websites such as http://www.curethalassemia.org/faq/
which includes 115 FAQ written by Dr. Pietro Sodani, Cure Thalassemia
co-founder & scientific coordinator.
At the same time, you should keep being updated on all new information
on any medical/drug advancement and progress in the area of treatment
and cure of thalassaemia that may indeed be appropriate for your case.
You may need all this information before taking any decisions. Please
consult with your treating doctor or the medical advisors of Thalassaemia
International Federation (TIF) for the best and most suitable option for you
or your child.
TIF’s website is regularly updated and constitutes a most reliable source
of information.
Frequently Asked Questions
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Useful sites:
Thalassaemia International Federation. Publications.
Available at https://thalassaemia.org.cy/
Karaiskakio Foundation/ Bone Marrow Donor Registry.
Available at https://karaiskakio.org.cy/bone-marrow-donor-registry-
main/?lang=en
EUROCORD Registry.
Available at http://www.eurocord.org/eurocord-registry.php
World Marrow Donor Association.
Available at https://www.wmda.info/
National Bone Marrow Donor Program’s Be the Match.
Available at https://bethematch.org/
Asia-Pacific Blood and Marrow Transplantation Group.
Available at https://www.apbmt.org/about
The South African Bone Marrow Registry.
Available at https://www.westerncape.gov.za/general-publication/south-
african-bone-marrow-register
EuroBloodNet
https://www.eurobloodnet.eu/
For any questions and/or feedback please contact us
Tel: +357 22 319 129 • Fax: +357 22 314 552
E-mail: thalassaemia@cytanet.com.cy
Website: http://thalassaemia.org.cy
Your Opinion Matters to Us!!
Educational leaflets
Other educational leaflets available:
Educational Leaflet 2:
Gene Therapy in β-thalassaemia
Educational Leaflet 3:
Clinical trials in β-thalassaemia
Educational Leaflet 4:
Iron chelation and monitoring or iron load in β-thalassaemia
Educational Leaflet 5:
Liver Disease in β-thalassaemia
Educational Leaflet 6:
MRI testing in β-thalassaemia
Educational Leaflet 7:
Effective Organ Monitoring in β-thalassaemia
Educational Leaflet 8:
Blood safety in thalassaemia and other haemoglobin disorders
Educational Leaflet 9:
Prevention of Thalassaemia and other haemoglobin disorders
Educational Leaflet 10:
New drugs and their impact on the pathophysiology and management of
thalassaemia
International Thalassaemia Day 2014 Photo Contest, 1st
Place
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TIF’s Educational Programme (in brief)
TheThalassaemiaInternationalFederation(TIF)hasdevelopedaninternationally-
recognised educational programme, with the objective of providing lifelong
education opportunities for healthcare professionals, patients and their families,
and raise awareness amongst policy makers and the community at at large.
These include:
1 Conferences and Workshops (national, regional, international)
2 Fellowships and Preceptorships
i. Renzo Galanello Fellowship Programme
ii.
TIF Preceptorships
3 Electronic and Mobile Learning
i. TIF e-Academy
- Thal e-course for patients/parents
- e-courses for health care professionals
ii.
ThaliMe app
iii. TIF Digital Library
TIF’s Publications
HOW TO ORDER https://thalassaemia.org.cy/publications/tif-publications/
Prepared by:
Farmakis, D.
Angastiniotis, M.
Eleftheriou, A.
Based on Cappellini, MD., Cohen, A., Porter, J., Taher, A., Viprakasit,
V. (2014). eds., Guidelines for the Management of Transfusion
Dependent Thalassaemia. 3rd
edition Thalassaemia International
Federation: TIF Publication No. 20.
Reviewer:
Cappellini, MD
TIF Publication No. 23
ISBN 978-9963-717-12-5
A Short Guide for
the Management of
Transfusion Dependent
Thalassaemia (TDT)
TIF Publication No. 23
ISBN 978-9963-717-12-5
A
SHORT
GUIDE
FOR
THE
MANAGEMENT
OF
TRANSFUSION
DEPENDENT
THALASSAEMIA
(TDT)
Prepared by:
Farmakis, D.
Angastiniotis, M.
Eleftheriou, A.
Based on Cappellini, MD., Cohen, A., Porter, J., Taher, A., Viprakasit, V.
(2014). eds., Guidelines for the Management of Transfusion Dependent
Thalassaemia. 3rd
edition. Thalassaemia International Federation:
TIF Publication No. 20.
Reviewer:
Cappellini, MD
This publication “A Short Guide for the Management of Transfusion
Dependent Thalassaemia (TDT)” received funding under an operating
grant from the European Union’s Health Programme (2014-2020).
Co-funded by
the Health Programme
of the European Union
HOW TO PARTICIPATE: https://thalassaemia.org.cy/education/
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A few words about Thalassaemia International Federation (TIF):
TIF Thalassaemia International Federation is an NGO founded in 1986
by a small number of patients and families representing National
Thalassaemia Associations in Cyprus, Greece, UK, USA, and Italy,
countries in which these diseases have been recognised as an
important matter for public health and where the first programmes
for prevention and management have been implemented.
MISSION To improve the survival and quality of life of patients with
thalassaemia through the promotion and support of: education,
advocacy and capacity building of patients’ and their families’
awareness and education programmes for the community
collaboration with national, regional and international health
authorities aiming to (a) prioritise thalassaemia on national,
regional and International health agendas; (b) develop and
implement national disease specific programmes for its effective
control, prevention and holistic care, and research programmes
and studies focused on the final, total cure (c) establish equal
access of every patient with thalassaemia to high quality health
and social care services provided through truly patient-centred
healthcare systems.
VISION Establishment of equal access of every patient with thalassaemia
to high quality health and social care services provided through
truly patient-centred healthcare systems.
The content of this Educational Leaflet for the Patient entitled ‘Bone Marrow Transplantation
(BMT) in β-thalassaemia represents the views of the author only and is his/her sole
responsibility; it cannot be considered to reflect the views of the European Commission and/
or the Consumers, Health, Agriculture and Food Executive Agency or any other body of the
European Union. The European Commission and the Agency do not accept any responsibility
for use that may be made of the information it contains.
Bone Marrow & Stem Cells