Cord Blood Transplants

SGH scores another first in stem cell transplants

Singapore General Hospital, in collaboration with the National University Hospital, has chalked up another world-class achievement in stem cell therapy. Doctors in the team treating a 5 year old boy with Thalassaemia Major have successfully performed the first case of cord blood transplant from an unrelated donor.

This is the first known case in the world of such a transplant conducted successfully for a patient with Thalassaemia Major. It marks yet another significant milestone in the development of leading edge stem cell therapy conducted at SGH. In 1995, SGH successfully performed the world's first recorded case of peripheral blood stem cell transplant from an unrelated donor for a patient with Thalassaemia Major. In that case, the stem cells were extracted through the blood instead of the conventional method of extraction from the bone marrow, making the ground breaking transplant the first of its kind in the world. Today, the patient is a healthy 10 year old boy attending primary school.

A lifeline for child with Thalassaemia Major
This current medical breakthrough involves a 5 year old Malaysian Chinese boy, born with Thalassaemia Major, a hereditary blood disorder where the body is unable to produce enough haemoglobin leaving the patient persistently and severely anaemic, requiring frequent and regular blood transfusions. Frequent blood transfusions often leave sufferers of Thalassaemia Major at risk of infections like hepatitis and possible iron overloading resulting in multiple organ failure. There is also a general immune suppressive effect. The majority of patients die of heart failure and do not have a life expectancy beyond 15 to 20 years. In this particular case, there were no matched sibling donors for either a bone marrow transplant or a cord blood transplant. When the boy was first referred to Associate Professor Patrick Tan, Head of the SGH Department of Haematology, a search with the Singapore Bone Marrow Donor Programme found no matched donor then. A/Prof Tan reviewed the case again this year, for consideration for a cord blood transplant and a new search was activated. Fortunately, a good cord blood sample was found and the cord blood transplant took place on 3 July 2001, at the National University Hospital, where the patient is being co-managed by the Department of Paediatrics.

Success factor - good sample of cord blood
One of the success factors attributed to the transplant was the availablity of a good sample of cord blood. The cord blood was collected from a Chinese baby delivered in SGH in 1998. The exceedingly high cell dose in the sample and the fact that it fully matched in the direction of rejection ensures a high chance of engraftment - a critical issue in all transplants for Thalassaemia Major. The cord blood sample contains 60-million cell dose per kilogram. Cell dose refers to the number of cells per kilogram of the patient's body weight and is a critical factor in predicting the patient's survival. The success of the cord blood transplant depends directly on the dose of stem cells received in the transplant - the larger the cell dose, the better the outcome. In this case, the cell dose contained in the sample is four times higher than the international recommended cell dose of 15-million cell dose per kilogram for cord blood transplant, which means that it has excellent potential for a successful transplant.


All signs pointing to complete recovery
Since the transplantation, the patient has not required any red cell transfusions. Preliminary blood studies show that he no longer has Thalassaemia Major and the
stem cells are functioning properly within his marrow by producing various kinds of blood cells. He is now producing normal red cell corpuscles unlike those seen in Thalassaemia Major, which are small and pale. The patient was discharged on 8 August, 36 days after the transplant. However he will still require to be monitored at the specialist clinic twice a week for 100 days.

Cord blood transplantation is a viable option
With the results indicating that the patient has been cured of Thalassaemia Major, cord blood transplantation from an unrelated donor has now been proven to be a valid alternative to bone marrow transplant from a sibling. This breakthrough achievement not only sets a milestone in the medical history of Singapore, it also highlights the successful outcome that arose from the close collaboration and teamwork between the SingHealth and the National Healthcare Group, the two healthcare clusters to which SGH and NUH belong to.

Double Cord Blood Transplant

Bone Marrow Transplant v/s Cord Blood Transplant

Article reproduced from Singapore General Hospital website

Bone Marrow Transplants v/s Cord Blood Transplants

what are the differences and what are the advantages of each ?

BONE MARROW TRANSPLANTATION
Bone marrow transplant is curative for Thalassaemia Major patients. When successful, it is an absolute cure.

Bone marrow allograft from matched siblings have been carried out extensively for Thalassaemia Major patients. Allograft refers to transplantation of tissue from another person, be it a sibling or an unrelated donor. There have been approximately 2,000 cases world-wide. In a good risk patient, the success rate is 90% . However, bone marrow allograft from matched unrelated donors for Thalassaemia Major patients is uncommon.

In general, there is a one-in-four chance of receiving a bone marrow transplant from a matched sibling. However, with decreasing family size, many patients are unable to find a matched sibling for bone marrow transplant.


CORD BLOOD TRANSPLANTATION
The umbilical cord provides a lifeline between mother and child during pregnancy. Like bone marrow, the umbilical cord is rich in haemopoietic stem cells, the same cells found in bone marrow which are the primitive cells from which all types of blood cells evolve.

Cord blood an opportunity for an alternative transplant source, besides bone marrow and peripheral blood stem cells, which will give new life to patients suffering from leukaemia, and other fatal blood disorders (Thalassaemia Major included).


Advantages of Cord Blood Transplants
Cord blood transplants offer some potential advantages over unrelated bone marrow transplants :

Lower risk of rejection - Patients transplanted with cord blood have a lower risk of severe graft-versus-host disease than those of unrelated bone marrow transplants, as the umbilical cord blood has not been exposed to outside antigens so the chance of graft-versus-host disease is reduced. Graft-versus-host disease is caused by the incompatibility between transplanted cells and their new host where the grafted cells reject their new host, causing a number of complications, including death.

Greater match tolerance - Cord blood transplant allows a mismatch, as the degree of histoincompatibility that can be tolerated is greater with cord blood than with bone marrow. In unrelated bone marrow transplants, a full tissue match is crucial. Unfortunately, most tissue typing has racial significance. It is very difficult to find any unrelated donor for an Indian patient for example, from the registries in Asia which are predominantly Chinese, or the USA, which are predominantly Caucasian. In cord blood transplants, two or even three mismatched antigens are acceptable. Significantly, cord blood transplant allows racial disparity.

Rapid availability - the preparation time for cord blood transplants is faster as the cord blood has been immunologically typed and is frozen, ready and available. Once a match is found, the cord blood only needs to be thawed and it can be used immediately, compared with the two to three months of preparation required for a normal marrow transplant.

Ease - harvesting cord blood is a painless, non-invasive procedure with no risk to the newborn of the mother.
No donor risk - in addition, there is no donor attrition and no donor risk as no donor is involved. For ordinary transplants, the selected matched donor may refuse donation or be unavailable. There is also a small risk to the donor, eg. from the general anaesthesia required during the marrow harvest. In constrast, when cord blood donation is required, the blood is simply taken out from the cord bank, processed in the laboratory and given to the donor.

Collecting cord blood
After the baby has been delivered, the umbilical cord is clamped, cut and separated from the baby. While waiting for the placenta to be delivered, the physician will collect the cord blood by inserting a needle into the umbilical vein after cleansing the cord. The entire process is non-invasive, painless and does not interfere with the birthing process.

Success factor - good sample of cord blood
A critical issue in all transplants for Thalassaemia Major is the availability of a good sample of cord blood. The exceedingly high cell dose in the sample collected for this transplant and the fact that it fully matched in the direction of rejection ensured a high chance of engraftment.

The cell dose in the cord blood is important to the success of the transplant because the larger the cell dose, the better the coutcome. In this case, the cell dose contained in the sample was 60-million cell dose per kilogram, four times higher than the international recommended cell dose of 15-million cell dose per kilogram.


Our local Cord Blood Registry - the first in Asia
Singapore is the first country in Asia to set up a functional cord blood bank. The SGH Department of Haematology, in collaboration with Singapore's Bone Marrow Donor Programme, started the cord blood collection programme in August 1997.

The Obstetrics and Gynaecology departments of SGH, NUH and a few private hospitals have been actively supporting the programme. There are now about 1,000 cord blood units stored at the cord blood bank.

As placentas and cords do not contain a set volume of blood, the stem cells contained most cord blood collection are usually sufficient for a small child. As a result, cord blood transplants are for now limited for paediatric patients.

© Singapore General Hospital 15 August 2001

Article reproduced from Singapore General Hospital website

L1 - Journey through the years

Deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one) alias L1, Kelfer, Ferriprox

Professor George J. Kontoghiorghes
Postgraduate Research Institute Science, Technology, Environment and Medicine
Ammochostou 3, CY 3021 Limassol, Cyprus. Tel: ++3575734615, e mail: pri_gjk@cylink.com.cy

Deferiprone is the first oral iron chelator used clinically, mainly in thalassaemia patients, where the annual birth rate worldwide is estimated to be 100000. Deferiprone belongs to the family of the alpha - ketohydroxpyridines, a relatively new class of chelating agents, some of which are naturally occurring. These have high affinity for binding iron and are able to remove it from proteins that are transporting and storing it in the body, largely sparing other biologically important metals. These chelators are stable in conditions that exist in the human digestive system and are readily absorbed.

Deferiprone has undergone extensive trials in hundreds of patients all over the world and has proved to be orally effective in removing excess iron from the body. Studies show that deferiprone is rapidly absorbed from the stomach. It appears in the blood minutes after the capsules are swallowed. In each patient, removal and excretion of iron depends on the dose and frequency of administration of the drug and the amount of iron overload. The major adverse effects, which have been observed in overall about 10% of the patients during worldwide clinical trials over a period of ten years, have been transient musculoskeletal and joint pains, neutropenia and agranulocytosis , gastric intolerance and zinc deficiency. Of these, perhaps the most disturbing is agranulocytosis, affecting less than 0.6% of the patients. In patients with agranulocytosis a substantial reduction or total absence of a group of white cells called granulocytes is observed, which amounts to rendering the body's immune system fatally weak.

This is the reason the focus of the mandatory monitoring procedure is primarily on levels of white blood cells and platelets. The monitoring not only helps to safeguard the well being of the patient but yields valuable data that can contribute to the development of a diagnostic method for agranulocytosis, its prevention and general improvement of the therapy with Deferiprone.

The Journey across the years:

1981.Discovery, design, synthesis and physicochemical characterization.

1981-82. Iron binding, protein and cell studies in-vitro. Animal studies.
1982. Naming of L1 and other alpha - ketohydroxpyridines.
1983. Patented in the UK. Later patented in the USA, EEC and some other countries.
1982-86. Intensive chemical, biochemical, cell and animal studies.
1986. DHSS grants permission for clinical trials in UK.
1987. Simple, cheap synthesis of L1. First ever clinical trials in London.
1988. Multicenter clinical trials begin worldwide.
1989. First publications on joint/musculoskeletal toxicity and agranulocytosis ( London ).
1990. Pharmacokinetic and metabolic properties characterisation of L1 in patients.
1992. Approved BAN and INN name for L1: Deferiprone.
1994. Registration of L1 in India, where now more patients are using L1 than desferal.
1995. Clinical use and multicentre clinical studies continue.
1998. Over 5000 patients in 35 countries have been using L1, some daily for over 10 years.
1999. Registration of L1 in European, South American and Asian countries.
2000. 10th International Conference in Oral Chelators for the treatment of Thalassaemia and other Diseases. 22nd-26th March, 2000. Limassol , Cyprus.

For more information contact Professor George J. Kontoghiorghes at the above address.

Reproduced from : UKTS Website

PS: The above does not mention 1987 : 400 Thals in India put on the largest trial for L1 the in the world.

Deferiprone Provides Significantly Greater Cardiac Protection

New Hope For Patients Afflicted with Rare Genetic Blood Disease: Study Finds Deferiprone Provides Significantly Greater Cardiac Protection

TORONTO, May 7 /CNW/ - Iron-induced heart disease is the major cause of death in patients with the genetic blood disorder, thalassemia. Now, a new published study in the journal Haematologica, reveals that long-term therapy with deferiprone (Ferriprox(TM)) provides greater protection of the heart from iron overload than standard therapy. The article, Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis, is the first study to examine the frequency of heart complications and survival in patients treated with Ferriprox in comparison with those treated with the standard therapy, deferoxamine (Desferal(TM)). The data revealed that Ferriprox had a major advantage in preventing iron-induced heart disease. The probability of worsening heart function over 5 years was five times more likely in the patients treated with deferoxamine than in those treated with Ferriprox.

The study coordinated by Dr. Antonio Piga of the Department of Pediatric Hematology, University of Turin, followed 129 patients with thalassemia major:
54 patients treated with Ferriprox and 75 patients treated with deferoxamine for an average of 6 years. At the initiation of the study, there was no significant difference in the percentage of patients with heart disease between the two treatment groups. At the end of the study, heart dysfunction, expressed as a worsening of pre-existing cardiac abnormality or development of new cardiac disease, was diagnosed in 2 (4%) of the Ferriprox-treated patients and in 15 (20%) of the deferoxamine-treated patients. None of the patients treated with Ferriprox died, while 3 of the patients treated with deferoxamine died because of irreversible worsening of their cardiac condition during the study period.

"Removal of iron from the body is important for transfusion-dependent patients, but the real benefit of an iron chelator is whether or not that effect translates into less morbidity and mortality. We have followed, very closely, hundreds of patients in our thalassemia center for decades. A few years after deferiprone was introduced, we began to suspect patients on this treatment were experiencing an advantage to the heart. On this basis, we conducted this retrospective examination of all of our patients who had been on continuous therapy with either chelator. The results are very encouraging for the patients.", stated Dr. Antonio Piga, lead author of the study.

Thalassemia major is a rare inherited anemia and affected children require blood transfusions every 2-4 weeks to survive. While the repeated transfusions extend survival to the 2nd or 3rd decade of life, iron in the transfused blood leads to a build up of toxic levels in the body, causing organ damage and premature death, primarily due to heart disease. Prior to the development of deferiprone, treatment for patients with iron overload was limited to deferoxamine, a drug that requires daily injections for 8-12 hours. Despite 30 years of use of deferoxamine, cardiac disease remains responsible for 70% of deaths in thalassemia patients. To provide an alternative medicine, Apotex initiated clinical trials of Ferriprox, an orally active iron chelator, in 1993. Presently, Ferriprox is approved as a life-saving alternative for patients in 25 countries including those of the European Union.

"There has been accumulating evidence from both animal and human studies
over the past decade that there might possibly be a cardioprotective effect with Ferriprox, but Dr. Piga's study is the first to demonstrate that Ferriprox reduces the toxicity of iron in the heart of patients with thalassemia and can extend survival", stated Dr. Fernando Tricta, Medical Director Apotex Inc. and a coauthor of the publication. "We look forward to further data that will add to these findings from a prospective and randomized study that is currently underway", concluded Tricta.

The really good news is for the patients. "We are excited about the hope the study provides to our patients. This is the fifth new study in the last year revealing important positive findings about deferiprone, and this one, about its benefits on the heart, is the most important. We anxiously await the availability of deferiprone as an option for treating our patients with thalassemia in the US.", stated Frank Somma, National President of the organization.

Ferriprox(TM) is the trademark of Apotex Inc. for deferiprone, an orally
active iron chelator.
Desferal(TM) is the trademark of Novartis AG for deferoxamine, an
injectable iron chelator.

RE: The Status of Ferriprox at the Time of this Press Release:
Ferriprox is on the market in 25 countries where the medicine is approved as a second line indication in transfusion-dependent thalassemia. Agranulocytosis (a decline in white blood cells that fight infection, down to a level that may not protect against invading microorganisms) is a reversible, but serious adverse reaction to Ferriprox that has been reported in about 1% of patients on chronic treatment. Country-specific prescribing information is available from Apotex. Applications for approval of Ferriprox in the US, Canada and several other countries are expected to be filed in 2003 and 2004.

RE: The Claims Referred to in this Press Release:
While the scientific statements about the cardiac benefits of deferiprone described in this Press Release are based upon the studies that have been conducted, Apotex advocates the use of Ferriprox according to the specific indications in each of the respective countries in which it is sold.

Prescribing information is available from Apotex.

Article reproduced from Newswire Canada

Kelfer/L1

Kelfer

Deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one) alias L1

The world's first oral iron chelator

What is Kelfer ?
Kelfer (deferiprone) is a iron chelator administered in the form of capsules to patients of thalassaemia major. It is being sold in India since March 1995 commercially.

How does Kelfer act ?
Kelfer acts by combining with the excess iron in the body to form a complex which is excreted in the urine. This over a period of time leads to reduction in the iron overload in the body.

What is the usual dose of Kelfer ?
Studies have found that the optimum dose of Kelfer is 75 mg/kg/day in 2-4 divided doses taken with or without food. In some patients doses upto 100 mg/kg/day may be administered while in others lower doses of 50 mg/kg/day may be sufficient.

What are the side effects of Kelfer ?
In about 20% of patients, joint pains involve knees, hips, elbows or other joints. The pain may be accompanied by swelling in a few cases. This effect is completely reversible on discontinuation of the drug.

In about 12%, Kelfer can reduce white cell counts. This can be dangerous and may predispose the patients to infections. In such situations, the patient may develop fever sore throat etc. The drug should be immediately stopped, the treating physician consulted and appropriate therapy instituted. In some cases, hospitalization may be required till the counts come back to normal.

What are the precautions to be observed while taking Kelfer?
Patients taking Kelfer should be regularly monitored for their blood counts and joint pains. If the total white blood cells falls below 3000/cc of blood or absolute neutrophil counts to below 1500/cc, Kelfer should be immediately discontinued. If the patient develops fever or sore throat, the drug should be discontinued, a blood should be immediately done and if the counts are low (as mentioned above), the physician should be seen immediately.

How is Kelfer available to patients ?
Kelfer is manufactured by Cipla Ltd and is available to patients through Cipla sales offices all over India under certain guidelines. Physicians have to fil up special prescription and patient consent forms prior to initiating therapy with Kelfer. The drug is supplied for a period of 13 months. Subsequently, everytime Kelfer is purchased, a fresh prescription order form has to be filled.

What is the cost of Kelfer therapy ?
For the patients in India the monthly cost of Kelfer therapy works out to Rs.2,000/- on an average with one 250 mg capsule costing Rs.9.75 and one 500 mg capsule costing Rs.16.00

How has Kelfer helped patients of thalassaemia in India ?
The introduction of Kelfer has led to more number of patients taking chelation therapy due to its excellent compliance and low cost. More than 1000 patients have taken Kelfer with good results. Overall, this has led to a better quality of life for thalassaemic patients.

Journey through the years

Study finds Deferiprone (Kelfer/L1/Ferriprox) provides significantly greater cardiac protection

My story

Introduction
I am the only son of my parents.

I was born with a genetic blood disorder known as Thalassaemia Major (TM). A person suffering from TM does not make enough haemoglobin or Red Blood Corpuscles (RBC’s). I have this because both my parents have half a defective gene for Thalassaemia, i.e. they are both Thalassaemia Minor. That does not mean they are sick or have an illness, except that they are slightly anaemic.

I was diagnosed as TM when I was 8 months old. In those days, no one knew anything about Thalassaemia. Even doctors knew very little, therefore it was very tough on my parents to face the facts of my condition and learn to cope with it. As it is with all Indians, my parents accepted it as their fate and perhaps it is a suffering caused by their own karma or a curse carried on from a previous life.

Treatment
My early childhood was just like that of every other child. Only my parents were somewhat overprotective. I grew up with TM without really knowing that I was seriously sick. As treatment for my illness, I was being given a blood transfusion once every six weeks.

Over the years, because I have grown and my body volume has increased, the transfusion regimen has reached a weekly frequency. This frequency is necessary because in our country we encounter many problems, such as non-availability of donor blood, quality and haemoglobin level of the blood, the restricted hours of the transfusion centre, etc. In the Government and NGO facilities, even a weekly frequency is often stretched to 12-13 days due to shortage of blood and other administrative hassles. I have no choice but to put up with all this because the expenses involved are affordable at about Rs. 150/- (US$ 3.5) per transfusion.

If I were to avail of the services offered by private blood banks or nursing homes, I would not only have to bring my own donor for blood, but also spend about Rs. 1500/- (US$ 35) per transfusion. This appears to be quite cheap compared to the expenses for similar services in the UK or USA. However, one must not lose sight of the fact that my father earns about Rs. 8000/- (US$ 225per month). If I receive four transfusions a month, the expenses would take away a large part of my dad’s earnings. My family can be included in the upper middle class income group. Consider what would be the plight of people belonging to middle and lower income groups.

Respectively taking all this blood transfusions leads to another problem i.e. from overload.

Due to biological reasons excess iron starts accumulating in the body and interferes with the functioning of the various organs in the body. To remove this excess iron, I started taking Desferal as early as 1977. Perhaps I was the first Thalassaemia in India to do so. Of course, the drug was not available locally and had to be imported. My father’s cousins and friends, whenever they travelled to London or Rome, used to bring a couple of boxes of Desferal with them. The first time I took one vial of Deferral in 5ml of distilled water is something I remember very well. Dr. Asha veer, a Haematologist, injected the whole syringe in one go into my bum. I could not sit straight for two days. She was a good doctor. Unfortunately, she expired due to cancer some years later. She was the type of doctor who was dedicated to her work and hence I think I should her in this write up.

After some years, we came to know that for Desferal to be effective it has to be administered subcutaneously and over 8-10 hours of slow infusion with the help of an electronic pump as small as a pencil box. My parents purchased this pump in 1982 for a princely sum of Rs. 8000/- (US$225) at a time when my dad was earning approximately Rs. 1500/- (US$35) per month. In 1982, Desferal became locally available. If I were to take the doctor’s recommended dosage it would cost me Rs. 20000/- (US$ 520) per month. After taking Desferal for seven years my serum ferritin level reached a figure of 8000, a level which ultimately took a toll on my heart and liver. Then in 1989 a wonderful thing happened which was the end of Desferal for me.

A new oral iron chelating drug called Deferiprone (Kelfer) came on the scene. I started with one capsule of 500mg per day, reaching up to a peak of 12 capsules per day, the highest dose ever given to anyone on the trial. After me, two others got a similar dose later. Regardless of the side effects of the new drug, about which I have heard, the pill definitely works for me. Today my dosage is 7 capsules per day and my serum ferritin level is 1400, the lowest ever it has been in my entire life and the biggest benefit of all is the freedom from daily injections.

After the trials were over, the pill was made commercially available in 1995. Until then, I was getting the pill free of cost, but now I have to buy it. The cost is quite cheap compared to Desferal. I spend about Rs. 3500 (US$ 100) per month. According to the procedure prescribed by the FDA, I have to get my CBC done every month and a serum ferritin every six months. This way my doctor keeps a tab on signs of any side effects. I have not touched Desferal since about 8 years now and my iron overload has only improved dramatically for the better, thanks to Deferiprone.

Deferiprone in India is available through CIPLA a pharmaceutical company who carried on the tests for long years and then introduced Kelfer in the market. I hope all Thalassemic’s out there read this and be assured that we have reached a stage where the treatment is not all that cumbersome or expensive.

With the quality of my life improving I have started to look up to other aspects. I keep in touch with latest developments in and for Thalassemia through International meets and participation in local parent-patient organisation

I thank you kindly for taking your precious time out for reading this.

Update Early 2000
Things are really looking up now, I am presently employed in the IT industry, coming out of recession, have just started saving some money finally. This is really a short update, I know I will add another paragraph to this page after all the above was written in 1998, its 2000 now. Wow I made it to the minllenium.

Update May 2002
30 years old, 8 years on desferal and 12 years on Kelfer wow!!
I need to really keep a diary for everyday I live, for sure its gonna make juicy reading. I thought millenium was big now I am targeting 2005 WOW thats like the future. I dont know whats in store but its the first time I am looking to the future instead of sulking on whats past. BTW how do you like my domain!

What is thalassaemia?

Thalassemia consists of a group of inherited diseases of the blood. About 100,000 babies worldwide are born with severe forms of the disease each year. Thalassemia occurs most frequently in people of Italian, Greek, Middle Eastern, Southern Asian and African ancestry

What Are the Different Kinds of Thalassemia?
Thalassemia includes a number of different forms of anemia (red blood cell deficiency). The two main types are called alpha and beta thalassemias, depending on which part of an oxygen-carrying protein (called hemoglobin) is lacking in the red blood cells.

The most severe form of alpha thalassemia, which affects mainly individuals of Southeast Asian, Chinese and Filipino ancestry, results in fetal or newborn death. Most individuals with alpha thalassemia have milder forms of the disease, with varying degrees of anemia.

The remainder of this information sheet focuses on beta thalassemias, which range from very severe to having no effect on health.

Thalassemia major, the most severe form, is also called Cooley's anemia, named after the doctor who first described it in 1925.

Thalassemia intermedia is a mild Cooley's anemia.

Thalassemia minor (also called thalassemia trait) may cause no symptoms, but changes in the blood do occur.

How Does Thalassemia Affect a Child?
Most children with thalassemia major appear healthy at birth, but during the first year or two of life they become pale, listless and fussy, and have a poor appetite. They grow slowly and often develop jaundice (yellowing of the skin).

Without treatment, the spleen, liver, and heart soon become greatly enlarged. Bones become thin and brittle; face bones become distorted, and children with thalassemia often look alike. Heart failure and infection are the leading causes of death among children with untreated thalassemia major.

Children with thalassemia intermedia may develop some of the same complications, although in most cases, the course of the disease is mild for the first two decades of life.

What Is the Treatment?
The use of frequent blood transfusions and antibiotics has improved the outlook for children with thalassemia major. Children with thalassemia intermedia usually do not require transfusions, although they may be recommended if complications start to develop.

When children with thalassemia major are treated with frequent transfusions (generally every 3 to 4 weeks) aimed at keeping their hemoglobin level near normal, many of the complications of thalassemia can be prevented. This form of treatment, referred to as "hypertransfusion," enhances the child's growth and well-being, and usually prevents heart failure and bone deformities.

Unfortunately, repeated blood transfusions lead to a buildup of iron in the body, which can damage the heart, liver and other organs. A drug referred to as an iron chelator, an iron binding agent, can help rid the body of excess iron, preventing or delaying problems related to iron overload. The drug is usually administered daily via a mechanical pump that pumps the drug underneath the skin while the child is sleeping.

Children with thalassemia major who are treated with frequent blood transfusions and iron chelation live 20 to 30 years or longer. Since intensive chelation treatment was introduced only in the 1960s, continuing studies may show that treated individuals are living even longer.

Thalassemia has been cured using bone marrow transplants. However, this form of treatment is possible only for a small minority of patients who have a suitable bone marrow donor, and the transplant procedure is still risky and can result in death.

How Is the Disease Transmitted?
All forms of thalassemia are transmitted only through heredity. It cannot be caught from another child who has it. The disease is passed on through parents who carry the thalassemia gene in their cells. A "carrier" has one normal gene and one thalassemia gene in all body cells, a state sometimes called "thalassemia trait." Most carriers lead completely normal, healthy lives.

When two carriers become parents, there is a one-in-four chance that any child they have will inherit a thalassemia gene from each parent and have a severe form of the disease. There is a two-in-four chance that the child will inherit one of each kind of gene and become a carrier like its parents; and a one-in-four chance that the child will inherit two normal genes from its parents and be completely free of the disease or carrier state. These odds are the same for each pregnancy when both parents are carriers.

Is There a Test for Thalassemia?
Yes. Blood tests and family genetic studies can show whether an individual has thalassemia or is a carrier. In addition, prenatal testing using chorionic villus sampling (CVS) or amniocentesis can detect or rule out thalassemia in the fetus. Early diagnosis is important so that treatment can prevent as many complications as possible.

Can Thalassemia Be Prevented?
The disease can't be prevented at this time, but a program of health education, testing for the trait, genetic counseling, and prenatal diagnosis can provide families with full medical information to help them have healthy children.

People who think they may have or carry thalassemia can go to a genetic services center or clinic for the latest information and for testing. Individuals can be tested to find out if they are carriers. Genetic counselors then can help them make plans about future families.

What Research on Thalassemia Is Taking Place
Scientists are working on better ways to remove excess iron from the body in order to prevent or delay iron overload. They are developing and testing the effectiveness of oral iron-chelating drugs, which could greatly simplify treatment of this disease. March of Dimes grantees are among the many scientists seeking to develop an effective form of gene therapy that may someday offer a cure for thalassemia. Gene therapy may involve inserting a normal beta globin gene (the gene that is abnormal in this disease) into the patient's stem cells, the immature bone marrow cells that are the precursors of all other cells in the blood. Another form of gene therapy may involve using drugs or other methods to reactivate the patient's genes for fetal hemoglobin. All humans produce a fetal form of hemoglobin before birth; after birth, natural genetic switches "turn off" production of fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to activate these genetic switches so that they can make the blood cells of patients with thalassemia produce more fetal hemoglobin to compensate for their deficiency of adult hemoglobin. Initial studies of rare individuals with genetic traits that allow them to produce only fetal hemoglobin show that they are generally healthy, demonstrating that fetal hemoglobin can be a fine substitute for adult hemoglobin.

In addition, improved bone marrow transplantation methods may lead to wider use of the technique as a treatment for thalassemia. Bone marrow transplants have cured some cases of thalassemia but they are not widely used for the reasons discussed earlier.

Other Frequently Asked Questions about Thalassaemia

This article is the official text on thalassaemia taken from the
Thalassaemia International Federation Website