What is Sickle Cell Anaemia?

The disorder affects the red blood cells which contain a special protein called haemoglobin (Hb for short). The function of haemoglobin is to carry oxygen from the lungs to all parts of the body.
People with Sickle Cell Anaemia have Sickle haemoglobin (HbS) which is different from the normal haemoglobin (HbA). When sickle haemoglobin gives up its oxygen to the tissues, it sticks together to form long rods inside the red blood cells making these cells rigid and sickle-shaped. Normal red blood cells can bend and flex easily.

Because of their shape, sickled red blood cells can't squeeze through small blood vessels as easily as the almost donut-shaped normal cells. This can lead to these small blood vessels getting blocked which then stops the oxygen from getting through to where it is needed. This in turn can lead to severe pain and damage to organs.

Everyone has two copies of the gene for haemoglobin; one from their mother and one from their father. If one of these genes carries the instructions to make sickle haemoglobin (HbS) and the other carries the instructions to make normal haemoglobin (HbA) then the person has Sickle Cell Trait and is a carrier of the sickle haemoglobin gene. This means that this person has enough normal haemoglobin in their red blood cells to keep the cells flexible and they don't have the symptoms of the sickle cell disorders. They do however have to be careful when doing things where there is less oxygen than normal such as scuba diving, activities at high altitude and under general anaesthetics.

If both copies of the haemoglobin gene carry instructions to make sickle haemoglobin then this will be the only type of haemoglobin they can make and sickled cells can occur. These people have Sickle Cell Anaemia and can suffer from anaemia and severe pain. These severe attacks are known as Crises. Over time Sickle Cell sufferers can experience damage to organs such as liver, kidney, lungs, heart and spleen. Death can be a result.

Another problem is that red blood cells containing sickle haemoglobin do not live as long as the normal 120 days and this results in a chronic state of anaemia. In spite of this, a person with sickle cell disorder can attend school, college and work. People with sickle cell disorder need regular medical attention particularly before and after operations, dental extraction and during pregnancy. Many hospitals arrange follow-up appointments and it is advisable to discuss with the doctors questions concerning schooling, strenuous exercise, family planning, suitable types of employment and air travel. When a person is found to have a sickle cell disorder it is important that all members of the family be tested. They will not necessarily have sickle cell disorder but may be healthy carriers of a sickle cell trait.

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Questions and Answers on Bone Marrow and Cord Blood Stem Cell Transplants

Question:  What is the cost and the steps to consider for bone marrow transplant?

Answer:  Evaluation for Bone Marrow Transplantation is a long journey, because the risks and expenses are large. Here is an outline of what would need to be done to evaluate a child for possible bone marrow transplantation:

1) SICKLE CELL ELIGIBILITY -- determine whether your son has had severe enough sickle cell disease to make the risks of bone marrow transplant worthwhile. A summary of his medical history would be very helpful, focusing on whether he has had stroke and chronic transfusion, or very frequent hospital stays for pain or for lung problems, or other major sickle cell problems.

2) OTHER MEDICAL ISSUES --- You should make your doctor aware that your family is considering the bone marrow transplant (BMT) option. Ask the doctor to let us know whether there are any hidden medical problems that would influence the decision, such as chronic viral or other infections, problems with transfusion reactions, other medical problems unrelated to sickle cell, or anything else unusual. This does not have to be a lengthy or formal statement from the doctor at this point, more like a safety check to make sure that we are not missing any huge medical issues. A more complete medical record would be required later.

3) HLA-TYPING BLOOD TESTS --- Do immunologic typing (HLA typing) of your child and the relative with the highest probability of matching him - only brothers or sisters from the same parents are really potential donors, parents and half-siblings are very unlikely to match unless there was an unusual family tree. The HLA typing will cost several thousand dollars.  If the sibling is not a full HLA match, then it is very unlikely that BMT can be done.

4) PRE-BMT EVALUATION -- after all of the above steps, then a formal evaluation by the BMT team can begin. This will include a very detailed look at his medical history and current medical condition from head to toe, plus your family's ability to cope with the BMT process. Parents will need to plan to stay in the Atlanta with the patient for a minimum of 8 months for the pre-transplant evaluation, transplant stay, and post-transplant follow-up. A financial arrangement will need to be made, with an estimated cost for the BMT process of $150,000 to $250,000. An outside expert panel will review the case on ethical grounds.

5) BMT & early follow-up period - This is a risky process, and the statistics are that there is a 5% to 8% chance of death. Death can be caused by infection, bleeding, toxic effects of the treatment, or the new bone marrow engrafting and then attacking the rest of the body. There is also a 10% to 12% chance that the child could go through the BMT process but reject the new bone marrow, ending up still having sickle cell disease. Therefore, the overall success rate of BMT for sickle cell disease is approximately 80% to 85%, of being cured of sickle cell. These require close medical followup, often in and out of the hospital and office daily, and many medications daily. 

Question: How is the Cord Blood Stem Cell transplant like Bone Marrow transplant?

Answer: The preparation considerations are similar. the Cord Blood Stem Cell donor is unrelated and is an alternative for patient with out a brother or sister match. The cost , time, and follow-up are similar.

Question: I have a daughter that have sickle cell. If she would have a step sibling. Could she receive a bone narrow transplant if they match? What risk would it be if they do match an her body rejects the transplant?

Answer: The main concerns with sickle cell bone marrow transplantation are (1) the immunologic match between donor and recipient (HLA types) and (2) the health status of your daughter.

1) A full HLA match between brothers or sisters will have the very best chances for successful bone marrow transplant (BMT). Lesser degrees of match means greater chances of two bad outcomes:
1a) Graft Rejection (your child goes through the BMT process but at the end her own bone marrow grows back and she still has sickle cell disease) or 1b) Graft Versus Host Disease (GVHD - the transplanted marrow attacks the rest of your child's body as foreign tissue and can cause great damage.
1c) very seldom will a person have a full HLA match with half-siblings or parents, unless the family tree is very inbred (for example, everyone is from the same isolated village or clan and all are related to each other's cousins. Therefore, your child's step-sister would not have a high chance of being an HLA-matched donor for BMT.

2) In addition to the chances of the two types of problems listed above (Graft Rejection and GVHD), there is a third set of bad problems that are side effects of the harsh BMT treatment process. Death may occur due to overwhelming infection,uncontrollable bleeding, and failure of organs such as liver or kidney or lungs. The chances that these bad side effects will occur are probably greater if your child is in worse health going into transplant. Therefore, the general feeling among sickle cell doctors in North and South America is that the only patients with severe sickle cell complications should be offered BMT (because only then are the high risks worthwhile), but that they be in relatively good physical condition. Your child may or may not meet these eligibility criteria.

HLA Matching for Bone Marrow Transplant

Question: What does HLA matched mean?

Answer:The short answer is: HLA match = immunologic match.

The HLA markers on the surface of cells are what allows the body to recognize that these cells are its own ("self") or somebody else ("non-self"). Usually physicians will test for HLA in three classes: HLA-A, HLA-B, and HLA-DR, but there are additional surface markers which are not tested for. Each person has two possible inherited types in each of these classes, which are designated by numbers such as HLA-A4, A8 HLA-B27, B19 HLA- DR 1, 11. When all 6 of these are identical between a pair of siblings, they probably inherited all the same immunologic markers from their parents, and their cells cannot be distiguished as different by the immune system. This is the ideal set-up for a bone marrow donor and host: HLA-matched siblings.

Any mismatch in the HLA types of two siblings means that they inherited different types from their parents, and that would not be a good set-up for bone marrow transplant.

Finally, HLA-matching of unrelated people can be done, drawing from computerized registries of tens of thousands of people willing to be bone marrow donors (e.g. US National Marrow Donor Program, others in other countries). However, these unrelated people may match at all 6 of the markers for HLA-A, HLA-B,and HLA-DR but not match at some of the other surface markers because they are not from the same parents. The donor cells would have a fairly high chance of being recognized as foreign.

In each case of a mismatch, greater mismatch in HLA type means higher chances of two bad outcomes: (1) that donor cells would be attacked by the host immune system (graft rejection), or (2) the immune system that grows from the donor cells would attack the host (graft vs. host disease).  Also, children have less risk of graft vs host disease than adults with BMT.

For this reason, essentially all of the sickle cell BMT have been from HLA-matched sibling donors, for a child as the transplant recipient. The graft vs host disease rate has been relatively low for sickle cell children, but the graft rejection rate is higher (10-12%) than that for BMT as cancer treatment. Why the graft rejection rate is high for sickle cell BMT is not understood. Matched unrelated donors from the National Marrow Registry have not been used for sickle cell BMT, although one matched unrelated cord blood stem cell from the New York Cord Blood Registry has been used (Atlanta, Dr. Andrew Yeager)

You might find additional information about bone marrow transplant in broad terms from the National Marrow Registry website. Info about HLA typing may be available from organ donation and organ transplant centers, since the same HLA matching is done for transplants of heart, lungs, liver, kidney, etc. to prevent rejection of the transplanted organ.

Question: How can I get a consultation about bone marrow transplant

Answer: Write: aplatt@emory.edu or call the Comprehensive Sickle Cell Center at 404-616-3572 

 
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