Supportive care with monthly blood transfusions and appropriate medical follow-up will not cure your child, but if followed precisely, may allow your 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 your 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. Your child should be followed by a thalassemia center where the doctors will be able to advise you about supportive care and the different tests needed to assure that he or she will remains as healthy as possible.
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 your child at the time of transplant. It consists of replacing your child’s faulty bone marrow stem cells, from which red cells originate, with those obtained from a healthy compatible donor.
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. 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 can provides a 80-90% cure probability, with 5% mortality rate and a 10% chance of rejection (thus leaving the child thalassemic). These results have been reproduced in Cure2Children partner health centers in developing countries in Pakistan and India. Children with Hepatitis C can also be successfully transplanted.
HLA-typing is a test that will enable you to test the compatibility between your child and potential donor. HLA-typing can be performed in most countries. Costs and reliability however are quite variable. Cure2Children may provide assistance for this initial critical step toward a cure by BMT.
The cost of transplant varies and may range from 150,000 USD in western countries. However, Cure2Children has been able to teach medical centers in developing countries to conduct the procedure for no more than 15,000 USD with similar or better results in patients with the right conditions for the procedure. Cure2Children partners with local medical centers to offer BMT at a non-profit rate of 15,000 USD or less.
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.
While bone marrow transplantation offers a cure from thalassemia, it cannot be administered without very high chances of permanent infertility. Life long supportive care and blood transfusions, on the other hand, may allow the possibility of having children. This may change with time.
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. Late rejections and transplant-related complications, however, may occur and regular check up should be carried out at least for the first years following the BMT, after which the child should resume life as normal without thalassemia.
Bone Marrow Transplantation should be done as soon as possible, while the child is still young. In the best possible situation, however, a transplant can be safely postponed to 6-8 years of age.
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 Kelfer), or desferasirox (Asunra or Exjade). However, all these drugs may have significant side effects.
Additionally, while the cost of appropriate chelation therapy is variable, it is generally more than $5,000 USD per year. In developing countries the main problem remains access to care and the cost of drugs for chelation, which are well above the average income. Without access to regular chelation therapy and medical follow ups, the majority of children with thalassemia do not reach the age of 10. Some centers may provide subsidized drugs and care.
Mother, father, and first-degree relatives could be matches, especially if the parents are related. It might be worthwhile evaluating by HLA typing.
If you are considering having more children keep in mind that the risk of having a child with thalassemia is 25%, and the chance of having a matched healthy sibling is slightly less. There is a 50% chance that your new child will be a thalassemia carrier like you, however this is not a contraindication to donating bone marrow. Prenatal diagnosis by chorionic villus sampling, which is commonly performed in most countries, can rule out thalassemia and establish if the embryo is HLA matched early during pregnancy, generally by the 12-13th week. See also preimplantation diagnosis.
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.
If no sibling is available you should provide your child with optimal care and wait for less risky alternative transplant modalities or gene therapy.
Best results and most experience is with standard Bone Marrow Transplantation. For thalassemia there is no strong evidence that cord blood is superior to bone marrow. Thus cord blood collection and storage from a healthy newborn sibling is not considered an absolute requirement. Bone marrow collection can be safely performed on the healthy matched sibling as early as 6 months of life.
Transplant from mother (called Haploidentical Transplant), currently has a success rate in the range of 50% and a 20% mortality risk, these results, however, may improve with time. The cost is around 200,000 USD in western countries and should still be considered as a non-standard procedure.
Transplantation form unrelated donors (bone marrow or cord blood) in Thalassemia generally requires extended compatibility and thus the chances of finding a suitable unrelated donor are not very high especially if the ethnic background is underrepresented in bone marrow donor registries. Unrelated transplant is more risky (and much more expensive).
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.
For related bone marrow donation (generally from a brother or a sister) there is really no age limit, a bone marrow harvest can be safely performed between 6 months and 60, years of age if the donor is in good health. It is only for unrelated (donor registries) bone marrow donation that the age limit is much narrower, generally between age 20 and 40.
It depends on what medical support you can rely on in your area, but is generally between 3 to 8 months.
Unfortunately many children in poor countries still get Hepatitis C virus (HCV) from multiple transfusions, however, bone marrow transplant outcome is not influenced by this infection. Actually BMT may be even more indicated because HCV worsen liver damage due to iron overload. If Hepatitis C, if still active two years after transplant, it should be treated and followed closely.
These answers have been prepared by:
- Dr. Lawrence Faulkner, Cure2Children medical team coordinator
- Dr. Sadaf Khalid, Cure2Children Pakistan branch coordinator