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.