Bone Marrow Transplant For Immune Deficiency in Children by Dr. Sagar Bhattad

• Bone Marrow – What is it?
• What is a Bone Marrow Transplant For Children?
• How Does a Bone Marrow Transplant Help a Child With Severe Immune Deficiency ?
• Is a Bone Marrow Transplant a Surgery?
• Types of Bone Marrow Transplant
• Types of Donors For Bone Marrow Transplant
• Why Does a Child Require Bone Marrow Transplant?
• Risks Involved in Bone Marrow Transplant For Immune Deficiency in Children
• How to Help My Child Get Ready For a BMT?
• What Happens During a Bone Marrow Transplant For a Child?
• What Happens After a Bone Marrow Transplant For a Child?

Bone Marrow – What is it?

First, let’s understand what exactly a bone marrow is.

The bone marrow is responsible for making stem cells and all other blood cells in the body. The stem cells will divide or differentiate to form red blood cells, white blood cells, platelets, or more stem cells in the body. These cells are extremely crucial for the optimal functioning of the human body.

The bone marrow is present in the center of the bones and is soft and spongy. When diseases like sickle cell anemia and certain cancers occur in a child, the healthy cells are destroyed. To protect the child, the bone marrow has to produce more healthy cells at a faster rate.

What is a Bone Marrow Transplant For Children?

A Bone Marrow Transplant (BMT) for children is a specialized treatment for certain diseases, including a few types of cancers and serious immune problems. These diseases affect the child’s bone marrow and blood cells. The BMT will remove the affected bone marrow and replace it with healthy bone marrow.

Chemotherapy is a treatment given to treat cancer, to destroy the cancer cells. Unfortunately, while destroying the cancer cells, it also destroys the healthy cells in the bone marrow. With continuous treatment or intense treatments, the bone marrow itself will be destroyed and will require replacement without the bone marrow producing healthy blood cells, it is not possible for the body to continue living.

The BMT does not only replace the affected bone marrow but will also enable stronger chemotherapy and radiotherapy treatment. This, in turn, will increase the chances for a better cure for certain cancers.

How Does a Bone Marrow Transplant Help a Child With a Serious Immune Deficiency?

A Bone Marrow Transplant offers hope for those children with cancers and other diseases that do not respond to conventional treatments. A transplant helps their bodies fight from within when treatments from outside are not sufficient. A Bone Marrow Transplant is also the treatment of choice for many serious Immune Deficiency diseases, wherein the child cannot fight infections. In most immune deficiencies in children, white blood cells are either absent or dysfunctional. This lack of white blood cells can be corrected by a Bone Marrow Transplant.

Is a Bone Marrow Transplant a Surgery?

No. Unlike a liver or kidney transplant, where one needs to performs a surgery to place a new organ in the body, BMT is not a surgical procedure. The stem cells collected from the donor are given to the child via a vein (like a blood transfusion). In most cases, strong medications (like chemotherapy) are also given.

Types of Bone Marrow Transplant

Bone marrow transplants can be done in three different ways depending on how the stem cells are collected. They are:

1. Autologous Bone Marrow Transplant

In this method of BMT, the child itself is the donor. They do not depend on an external source for healthy bone marrow. This type of transplant is useful to treat a few solid cancers (eg: neuroblastoma). This is not useful in the case of genetic diseases or Immune Deficiencies, or Blood cancers.

2. Allogenic Bone Marrow Transplant

Here an external donor gives the bone marrow for your child. The donor will most likely be a relative who shares a genetic type. Each one of us has a HLA type. In BMT, donor and the child are matched for this HLA type. In most cases, the allogeneic donors will be the child’s own siblings, parents, etc. They are the optimal donors for the child.

In some cases where a donor match cannot be found within the family, external donors are searched for. These donors are found from the donor registry. They are called the Matched Unrelated Donor (MUD).

In allogenic or autologous transplant, the stem cells can be collected from the donor in one of the following ways –

a) Peripheral Blood Stem Cell (PBSCs)

The stem cells floating in your child’s blood are collected by a method called apheresis. The collected peripheral blood stem cells from the donor are given to the child.

b) Bone Marrow Harvest

This method involves a needle being placed directly into the bone marrow – the soft center of the bones. The bone marrow is collected via these needles.

3) Umbilical Cord Blood Transplant

In an umbilical cord blood transplant, the stem cells are taken from the umbilical cord right after the birth of a child. The stem cells are tested for their viability and type; they are counted and then frozen for storage until they are required.

Stem cell banking has gained a lot of importance and momentum in recent years due to this medical breakthrough. The stem cells can be the child’s own stem cells or an external donor. The match is again searched and found from the donor list. It must be noted that stem cells of the child will not be useful to treat genetic diseases in the same child, as it is likely that the stem cells have the same genetic issue.

Types of Donors For Bone Marrow Transplant

The types of donors for a bone marrow transplant are:

1. Optimal Donors

An optimal donor is mostly a sibling or a close relative who has an identical Histocompatible (HLA) type of tissue like the child. There is a one in four chance that a sibling will be HLA compatible – meaning the same two sets of HLA genes.  For a parent to be an optimal donor, the chances are much lesser as both parents mostly won’t share the same HLA type. Parents are usually half-match, however, on rare occasions, one of the parents may be a full match. 

2. Partially Matched Donors

A parent as mentioned above, will rarely be fully compatible. However, they will always be half compatible (haplocompatible) as they have given 50% of the genes to the child.

This is a more elaborate and riskier process than using an optimal donor. Here the stem cells are treated after collection. The treatment will deplete the stem cells of certain T lymphocytes to prevent a fatal complication called  graft versus host disease ( GvHD ) . The chances of these, T cells depleted bone marrow to work is lesser than optimal donors.

3. Matched Unrelated Donor

In case no matched sibling is available, doctors would suggest a search from the HLA donor registry to look for a matched unrelated donor. The chances of finding a donor in the registry is small but it’s worth a try.

Why Does a Child Require Bone Marrow Transplant?

As mentioned earlier, a bone marrow transplant will remove the diseased or affected bone marrow and replace it with healthy bone marrow. The BMT will help the child’s body produce healthy stem cells and blood cells that are important for survival.

There are so many medications and non-invasive treatments that do not have a big impact on the quality of life. When does a child cross this line and step into the list that requires something as complicated as a bone marrow transplant?

Here are some instances when a child will require a BMT:

1) When they are undergoing a high dose or prolonged chemotherapy for treatment of cancer, that has caused severe damage to their bone marrow, a BMT can replace the diseased bone marrow with a healthy bone marrow.

2) When chemotherapy has affected their immune system to a great extent and makes them prone to many infections and illnesses, a BMT can help regenerate the immune system to help it fight remaining cancer or other infected cells.

3) Cancers like kidney cancer, neuroblastoma, lymphoma, leukaemia, or brain tumours.

4) If cancer relapses.

5) Certain genetic disorders like:

• Hemoglobinopathy
• Sickle cell anemia
• Thalassemia
• Severe immunodeficiency syndromes
• Severe aplastic anemia
• Hurler syndrome

Bone marrow stem cells are the source of red blood cells, white blood cells and platelets. White blood cells and their proteins form the immune system. So, Bone Marrow Transplant would be useful in case any/all of these cell lines fail to work. Eg: White cells do not work (Immune Deficiency), Red cells are not formed properly (Sickle cell anemia, Thalassemia), Bone marrow has stopped working (Aplastic anemia) etc.

[Read : Primary Immunodeficiency in Children ]

Risks Involved in Bone Marrow Transplant For Immune Deficiency in Children

A bone marrow transplant for serious immune deficiencies in children is life saving, however it comes with it’s own risks and challenges. There are no two ways about it. However, doctors and researchers have strived hard to reduce the risks and the after effects, especially for children. The aim is to help the children recover and lead as healthy a life as possible without having to miss out on their “childhood”.

The risks vary from case to case. The various risk factors are:

• The age of the child
• The type of BMT
• The illness being treated
• Medications before and during the treatment (possible side effects, how it has affected the internal parts of the body, and the immune system itself)
• The difference in the tissue match between the donor and your child

Some of the common risks involved in a BMT for a child are:

1. Low Platelets

When the platelets are dangerously low, they can they can lead to serious bleeding.

2. Increased Infections

When the bone marrow does not function as required, the immune system becomes weak. A weakened immune system cannot fight off infections effectively, and the child gets weaker.

3. Pain

Chemotherapy and radiation can cause mouth sores and gastrointestinal irritation, which can be very painful for a child. Medications for mouth sores and pain can help alleviate the discomfort.

4. Diarrhea, Nausea, and Vomiting

Chemotherapy, and radiation can cause severe diarrhea and vomiting. For some, it can be just nausea. This, in turn, will cause a lot of weight loss and loss of appetite. Your child may not be able to eat enough to get all the nutrients required for a good recovery. The essential proteins and required calories may be given through an IV to help them.

5. Organ Damage

A BMT might cause short-term or long-term damage to the heart and liver. Your child will be under constant supervision to prevent any such damages. The chances of this complication are small.

6. Graft Failure

The stem cells transplanted to the body might not grow as expected in the bone marrow; this is known as a graft failure. Graft failure can happen due to insufficient stem cells transferred, infections or a relapse of the disease being treated. Such a failure will generally require another BMT.

7. GvHD

Graft-versus-Host-disease is when the donor’s transferred cells start attacking the host’s healthy cells instead of strengthening the immune system. Some of the common symptoms of GvHD can be diarrhea, breathing problems, stomach pain, and changes in skin, rashes, or fever. Certain medicines will be given to your child before the transplant to prevent this type of complication. GvHD can sometimes even be fatal.

[Read : Autoimmune Vs. Low Immunity]

How to Help My Child Get Ready For a BMT?

A bone marrow transplant can be hard on a child and the entire family. It can be very scary for your child. The doctors and the entire team of professionals handling your child’s BMT will guide you step by step.

Here is how you can help your child:

1. Keep Them Informed

When the medical team informs you about the procedure and the steps involved, relay the same thing to your child in the best way they can understand. Many parents may think it’s best to leave the child in the dark and not tell them details about the procedure, as it might scare them. It will definitely scare them, but it will be scarier to undergo the treatment without knowing what is being done to them.

2. Take the Tests

The team will then test your child physically. The various physical exams and tests will help them assess the situation and the child’s health. Be patient and supportive to your child. If they feel discomfort during the tests, do your best to pacify them and reduce the discomfort. Ensure one of you accompanies them for all tests. Do not let them go through it alone or with some caregiver. Emotional support is very important.

3. Prep For Transplant

They might ask your child to come to the medical center a week or 10 days before the transplant. A catheter will be placed in your child’s vein. Medicines and blood products will be given through this catheter to prepare your child for the procedure. Stay with them and help them through this difficult phase.

4. Answer Questions

Children generally are full of questions. In this case, the questions could be much more than what you could answer. Rather than silencing them and telling them that they won’t understand, try to answer them or get answers from the doctors. When they know what is happening to them, children can be more prepared and resilient.

5. Give In

Now is not the time to enforce or abide by all your parenting rules and boundaries. You need to give in and be lenient with a child who is undergoing a life-changing procedure that can have complications later. It is a very scary phase for them as well as you. If they throw tantrums, please understand it is because of fear and not “bad behavior”.

What Happens During a Bone Marrow Transplant For a Child?

It takes a long time to find a suitable donor or the perfect match for stem cells. Once the match is found, the doctors will hospitalize the child in a special room (to prevent any infection). They might give stronger chemotherapy or radiation, to kill all the defective and diseased cells in the bone marrow.

Killing defective cells will create more room for the new healthy cells to grow. This is called ablative or myeloablative therapy. It stops the bone marrow from making new cells. The bone marrow will become empty and provide enough room for the new cells to grow and to create a new system. Now, new blood cells will be made from the healthy cells that have been transferred.

Next, they will give new stem cells through the central venous catheter they fitted in your child’s chest, at the time of hospital admission. These healthy new stem cells will find their way to the empty bone marrow and start making new healthy cells.

This is a complicated procedure and will not be easy on your child. They might experience –

• Pain
• Hives
• Chills
• Fever
• Chest Pain

[Read : 10 Most Important Nutrients Needed For Strong Immune System in Kids]

What Happens After a Bone Marrow Transplant For a Child?

After the transplant, your child will be under close observation to ensure the new cells take to the body and start producing new cells. The medical team will keep checking your child for possible side effects or a graft failure or GvHD.

Your child will be at risk of infections as their bone marrow is literally emptied and replaced. They may experience the following:

• Vomiting, nausea, mouth sores, diarrhea, or weakness
• Bleeding
• Emotional distress/ post-traumatic reactions

List of Things Parents Need to be Prepared For

As a parent, you need to be prepared for the following possibilities or situations:

• Your child might have to stay for a few weeks in the hospital until their immune system is strong enough to let them step out of the sterile environment (typically 4-5 weeks).
• Your child will be given multiple antibiotics and medicines to help their body cope with the transfusion and lack of immunity.
• The doctor will prescribe medicines to prevent GvHD.
• Daily blood tests to monitor your child continuously.
• Engraftment usually takes about 15 – 25 days.
• It might take months or even years until your child’s immune system is strong enough for them to lead a regular life.
• Certain complications may develop even a few days after the BMT.
• Diet restrictions and lifestyle changes for your child.
• Regular tests and check-ups.

If all goes well, your child can eventually lead a healthy life. The experience could have changed your child emotionally and mentally too. You need to help and guide them patiently.

Conclusion

A bone marrow transplant can be tough on both the child as well as the family. It is not easy to see a child suffer that way and do nothing about it. It is a very unfortunate situation, and please remember to trust your doctor. If you are unable to, you need to change your doctor before you can go in for serious treatments or a transplant. Trust and patience are crucial in such situations. Bone marrow transplant is life-saving in many serious diseases (cancers or serious immune deficiencies), and sometimes, this is the only hope to save a sick child. Children who have successfully undergone a bone marrow transplant can lead a healthy life and go on to become productive citizens.

Read Also: Stem Cells Uses, Importance, and Potential Medical Applications