In an enviroment full of different patients
with severely debiliating diseases, doctors also learn to control their
emotions while treating them. And when these patients are children, you must be
extremely cautious and giving to help them for a healthy, long life. As a
doctor who is in this area since more than thirty years, I always make myself
believe that I am used to the most bitter tragedies of life, but when a guy
decides to leave this world, that is the end of your experience. I never
discussed with myself why I became a doctor, pediatrician, hematology/oncology
person expert in BMT. Maybe the heroic achievements might have attracted me,
but still I am not protected against the bumpy roads of my career.
Thalassemia patients were always in my
life, taking an important part of my daily bussiness. When I first started
pediatric hematology, thalassemic patients were with severe problems, and used
to die in early ages, but they are now quite healthy persons which you can not
understand their disease in daily life. As a pediatric hematologist who is also
involved in BMT, I would like to answer some frequently asked questions about
thalassemia and BMT.
What
Is Thalassemia?
Thalassemia is a group of genetic blood
disorders that cause severe anemia. They are also known as Mediterranean anemia
or Cooley’s Anemia. People born with this disease cannot make normal hemoglobin
(anemia) which is needed to produce healthy red blood cells. And needs
replacement of healthy red blood cells at least monthly to live a healthy life.
Who
carries Thalassemia?
People of Mediterranean, Middle Eastern, Chinese,
South Asian or African origin.
What
is Thalassemia Minor?
People with a thalassemia mutation only in
one gene are known as carriers or are said to have thalassemia minor.
Thalassemia minor results in no anemia or very slight anemia. People who are
carriers do not require blood transfusion or iron therapy, unless proven to be
iron deficient. They also do not need any iron chelation therapy.
Many people, from the areas of the world
where thalassemia is common, carry the gene for it on one chromosome, they are
called thalassemia minor and can easily be diagnosed using hemoglobin
electrophoresis which can identify a carrier of thalassemia. It is important to
identify a possible carrier of thalassemia (thalassemia minor) before marriage,
as a person with thalassemia minor has a 25% chance of having a baby with thalassemia major
if his/her mate also has thalassemia minor.
What
is Thalassemia Major?
There are three types of thalassemia -
thalassemia minor/trait, thalassemia intermedia, and thalassemia major. A
person with thalassemia intermedia has a moderately severe anemia. There is a wide range in the clinical
severity of this condition. Generally speaking, patients with thalassemia
intermedia need blood transfusions to improve their quality of life, but not in
order to survive. Most intermedia
patients do become transfusion dependent in order to avoid the complications
associated with chronic anemia. Individuals
with thalassemia major have a severe anemia that requires regular blood
transfusions (every 2-4 weeks) beginning early in childhood. These extensive,
lifelong blood transfusions lead to iron-overload which must be treated with
chelation therapy to prevent organ failure.
Children born with thalassemia major usually develop the symptoms of
severe anemia within the first year of life. Lacking the ability to produce
normal adult hemoglobin, children with thalassemia major are chronically
fatigued, fail to thrive and do not grow normally.
Prolonged anemia will cause bone deformities
and eventually will lead to death within the first decade of life. The only
treatment to combat severe anemia is regular blood transfusions.
How
can Thalassemia be treated?
Regular blood transfusions allow patients
with thalassemia to grow normally and be active. Unfortunately, transfusions
result in deadly accumulation of iron in the heart and liver. Iron also
cummulates in other places like endocrine organs, skin, pancreas, etc. If the
excess iron is not removed then the patients may suffer from a premature death
due to iron overload.
Nowadays, drugs designed to remove excess
iron (iron chelators) have significantly changed the prognosis of thalassemia.
Patients can grow and develop normally, with relatively normal heart and liver
functions. Patients are living longer and having families of their own. Supportive
care with monthly blood transfusions and appropriate medical follow-up will not
cure the patient, but if followed precisely, may allow the child to live up to
40 or 50 years of age with a good quality of life. The main issue is access to
appropriate supportive care and blood transfusions. It is particularly
important to assure safe blood, preferably not from family members but from
volunteer donors. Pre-transfusion hemoglobin should be kept above 9 g/dL. After
the initial 15-20 transfusions, iron from transfused red cells starts to
accumulate and may cause harm to the child’s body, especially the heart and
liver. This iron build-up is evaluated by measuring ferritin blood levels. When
ferritin levels rise above 1,000 ng/mL its time to start iron-removing
(chelation) therapy. In general the iron accumulating from multiple
transfusions can be removed from the body quite effectively with chelation
therapy, which employs drugs like deferoxamine (Desferal), deferiprone
(Ferriprox), or desferasirox (Exjade). However, all these drugs may have
significant side effects. The child should be followed by a thalassemia center
where the doctors will be able to advise about supportive care and the
different tests needed to assure that he or she will remain as healthy as
possible.
Current treatments allow thalassemia
patients to live relatively normal lives, however, a cure remains to be found. The
only cure for thalassemia is bone marrow transplantation. The highest success rate for bone marrow
transplantation is having a sibling bone marrow donor. However, gene therapy is currently in
clinical trials and appears to be a promising cure in the horizon using each
thalassemia patient’s own stem cells. The genetic cause of thalassemia was one
of the first genes discovered in the 1970′s, yet 40 years later, gene therapy
still eludes thalassemia patients.
What
is the life expectancy of a child with Thalassemia?
The answers are unknown and largely depend
on the form of thalassemia and the medical care a patient is receiving. In past years and even presently in some
countries with inadequate medical treatment it can be childhood to early adult
years. However, in developed countries
with medical advancements, people are living in to their > 50’s. People with thalassemia minor have a normal
life expectancy and that is becoming the reality for intermedia and major
patients as well.
What
is the definitive treatment of a child with thalassemia?
Bone Marrow Transplantation (BMT) is the
only definitive cure for thalassemia, but it has its risks. These risks depend
mostly on availability of a compatible family donor, generally a sibling, and
the age and health of the child at the time of transplantation. It consists of
replacing the child’s faulty bone marrow stem cells, from which red cells
originate, with those obtained from a healthy compatible donor.
What
is the success rate for using Bone Marrow Transplantation (BMT) to cure
thalassemia?
Provided there is a compatible family donor
and that the patient is in the right conditions for the procedure, Bone Marrow
Transplantation (BMT) is generally before age five and without liver
enlargement might be recommended. However, in older children or in those with
very high ferritin levels (greater than 2.000 ng/ml), liver or spleen
enlargement, intensive treatment with chelation drugs and hydroxyurea can
improve transplant results.
BMT as a way of curing children with
thalassemia has been successfully performed for almost 30 years in a total of
more than 3,000 patients worldwide. BMT can provide a 80-90% cure probability,
with 5% mortality rate and a 10% chance of rejection (thus leaving the child
thalassemic). On average a BMT requires a hospital stay of 1.5 to 2 months. Most
children become transfusion-independent within a month of the transplant. The
early or late side effects of BMT (Rejection, GvHD, Veno-occlusive Disease
(VOD), infections, organ dysfunctions, sterility, etc.) might be seen during
the procedure. Late rejections and transplant-related complications may occur
and regular check up should be carried out at least for the first year
following the BMT, after which the child should resume life as normal without
thalassemia.
Other options like transplantation from
unrelated marrow donor registries, cord blood banks or from a partially matched
family member (generally the mother) have been performed successfully but are
currently quite expensive and risky. In the context of an effective supportive
care alternative, they should probably be considered if transfusions and/or
drugs cannot be tolerated or are not accessible.
Gene therapy, although significant progress
has been made, will not be routinely available for at least some years, maybe
another decade.
What
are the risks for donors & how bone marrow is collected from donor?
Generally there is no risk to donor even if
he/she is Thalassemia minor and bone marrow collected from him/her is replaced
by their body without any pain. Bone marrow from donor is collected under
general anesthesia from upper part of hip bone.