Finding the Best Donors for Bone Marrow Transplantation

Bone marrow is the highly cellular soft area in the hollow of bones where all the blood cells are produced before circulating in to the blood stream. Whenever primary cells of the bone marrow (that are also called stem cells which can grow and mature in to different cell types) become cancerous they lead to different types of blood cancers. These stem cells need to be replaced with healthy stem cells from a genetically matching donor so that the marrow starts producing healthy blood cells and the cancer can be cured. This procedure is called bone marrow transplant (BMT) or stem cell transplant.

 

Why is bone marrow important?

Bone marrow is a soft, spongy tissue inside the bones. Bone marrow contains hematopoietic stem cells, which are immature cells that can develop into these blood cells: 

• Red blood cells (RBC) that carry oxygen throughout the body
• White blood cells (WBC) that boost our immune system and fights infections
• Platelets that are essential for blood clotting

Bone marrow also plays an important role in the body’s immune system. As a result, the diseased bone marrow will not be able to produce necessary cells that can eventually affect the overall immunity of the patients leading to life threatening infections.

Indications for bone marrow transplantation

• Blood cancers, such as leukemia, lymphoma, myelodysplasia, Hodgkin’s disease, multiple myeloma
• Diseases that affect the production of bone marrow cells, such as aplastic anemia, congenital neutropenia, sickle cell anemia, POEMS syndrome, neuroblastoma

Transplantation criteria and requirements

Bone marrow transplantation is a rigorous medical procedure and is not recommended for everyone.   The healthcare team would evaluate the patient by conducting various medical tests, a complete physical examination and psychosocial evaluations to decide whether that patient is a suitable candidate for bone marrow transplantation.

 Eligibility criteria

You could be a healthy donor for a bone marrow transplantation if you meet the following criteria:

1. Age: Healthy individuals between the ages of 18 to 60 years could be ideal candidates for a bone marrow transplantation.
2. Weight:  In order to register as a potential blood stem cell donor, the maximum Body-Mass-Index (BMI) limit is 40 kg/m2. Additionally, if a person’s weight is  below 50kg then he/she is not eligible for donating their blood stem.
3. Health conditions: People with the following conditions are not eligible for donating their stem cells:

• Conditions that affect the central nervous system or any mental illness
• Autoimmune diseases
• Chronic conditions, such as diabetes or rheumatism
• Chronic heart diseases
• Chronic lung diseases
• Infectious diseases, such as HIV, hepatitis B or hepatitis C, and syphilis
• Blood disorders 

Pregnancy:  Pregnant women are eligible to register as blood stem cell donors.  But, they cannot donate until they fully recover after the delivery.

Types of transplantation

There are mainly two types of transplantation based on who donates the stem cells:

1. Autologous: In this transplant, the stem cells are collected from the same person who will get the transplant i.e., the patient is their own donor.
2. Allogeneic: In this transplant, the stem cells are collected from another person referred to as donor. A donor can be anyone among the patient’s family, friend or can even be a matched unrelated person.

In addition to the above types, another type of bone marrow transplantation is Umbilical cord transplant. In this type the stem cells are taken from the umbilical cord of an infant immediately after delivery. These stem cells are tested, typed, counted and frozen until they are required for transplantation. This procedure is still under research evaluation and some encouraging results have been noted but still it is not standard practice.

Why are donors needed for bone marrow transplantations?

If you are undergoing an allogeneic transplantation, you will need to search for a stem cell donor. In most cases, your transplant team will work with you to find a suitable donor. There are various steps to ensure that the donor is the best match for the patient and that the donor is medically fit to donate stem cells.  

Types of bone marrow transplantation donors

1. Optimal donors: These donors have an identical HLA tissue typing, and are mostly a relative of the recipient, usually a sibling or, in rare cases, a parent or grandparent.
2. Partially matched donors: These donors have a 50% HLA tissue match (always half matched, or haplo compatible) with the recipient. Biologic parents are always partially matched donors for the recipient.
3. Alternative donors: These donors are unrelated to the recipient. They are healthy individuals with matching HLA tissue typing with the patient and are willing to donate bone marrow stem cells.
4. Autologous donors:  In this type, the recipients themselves are the donors. Here the stem cells that circulate in the bloodstream are collected and are frozen or stored for later use. The recipient can donate only when his or her body produces enough healthy bone marrow cells. 

How can you be a donor for bone marrow transplantation?

If you are planning to donate stem cells, you have to register in the National Marrow Donor Program (NMDP) which is a USA based registry of potential donors with database of worldwide bone marrow donors. You will be asked to update your health information and to participate in additional testing to make sure that donation is safe for both you and the patient. 

To find out whether you are the best match for the patient, a blood test known as human leukocyte antigen (HLA) typing, is carried out to check the compatibility of your stem cells with that of the recipient. You can’t donate stem cells if you’re not a match. 

In such cases, your name will be entered in the register as a potential donor. This helps doctors find donors for their patients as quickly as possible from anywhere in the world. This directory is not comprehensively subscribed in India as yet.

 

Selecting the best donor for a patient

The doctors will choose the potential donors who appear to match the patient at a basic level. Basic level evaluation includes: physical examination, blood tests and review of medical history. Special blood studies on the patient and donors may be needed:

• Human Leukocyte Antigen (HLA) Test 

It is also referred to as tissue typing or histocompatibility typing. This special blood test analyzes specific proteins (HLAs) on the surface of white blood cells and other cells that act as markers and will recognize which cells belong to the body. The donor’s blood stem cells must have similar genetic markers as that of the patient. Hence, a close HLA match between donor and patient is the most important matching factor.

HLA test is performed as follows:

• Blood samples drawn from the vein  or through a swab cell from the inside of the cheek of the donor is collected.
• The sample is then sent to a special DNA testing laboratory.
• The samples are then analysed to find out if the person is an HLA-match to be a donor.

 

• High resolution DNA typing

This test analyses how much the donor and recipient cells will recognize one another as same or different. The differences in the value indicates the chance of stem cell rejection or graft vs. host disease. It means that the immune cells of the transplanted tissue would recognize the recipient’s cells as “foreign” and will attack it.

If the recipient sample matches with the donor, then the healthcare team will initiate the donation procedure.

Collection of stem cells 

Once the donor is selected for bone marrow transplantation, the healthcare team will brief the donor about the procedure, recovery process, the risks and associated side effects. If the donor agrees to undergo the procedure, then he or she will have to sign a consent form.

The collection of stem cells from the donor is known as harvesting. The donor stem cells can be collected in two ways. The methods are as follows:

 

• Bone marrow harvest 

This is a minor surgical procedure performed under general anaesthesia; it is often performed in a hospital operating room. The site of collection will be the rear pelvic bone where a large quantity of bone marrow is located. A syringe is used to extract the bone marrow, the amount would depend on the weight of the receiver. A sterile bandage will be applied to the site after the procedure.

 

• Apheresis 

It is a medical procedure that involves the collection of stem cells from the bloodstream. It involves the removal of whole blood from a donor and is centrifuged to obtain individual components. 

Before apheresis is performed, the numbers of stem cells must be increased, which is done by administering certain growth factor medications like filgrastim or plerixifor over a four to five-day period.

Once the required count is reached, the blood is drawn from a vein of the donor. The stem cells are then separated from the whole blood using a centrifuge. The extracted stem cells are normally kept in a freezer until transplantation. 

There aren’t many risks for donors and serious complications are rare. Rare complications may include anesthesia reactions, infection, muscle damage, fatigue, etc. Once the donation procedure is complete, you may be advised to take calcium supplements for a few months.

The stem cell harvesting in autologous stem cell transplantation involves the following steps:

 

• Stem cell mobilisation:

Before harvesting, the patient gets treated with certain medications like filgrastim or plerixafor for four to five days. These medicines increase the number of stem cells and also enhance the movement of stem cells from the bone marrow to bloodstream.

 

• Apheresis:

The stem cells are collected from the patient’s peripheral bloodstream. For stem cell collection, blood is withdrawn from the vein of a patient’s arm. Now, the stem cells are separated from blood by using an apheresis machine. This process may take a few hours and is repeated until the appropriate amount of stem cells are collected. 

 

• Processing:

After harvesting, a preservative is added to the stem cells and are cryopreserved (frozen) for later use. The rest of the blood is returned to the patient’s body.

Once the stem cells are collected, the doctor will administer high doses of chemotherapy and radiation therapy to destroy the cancer cells. This is known as conditioning. The transplant is typically done two to three days after these therapies are completed. 

According to various studies, there is a one in four chance of patients’ stem cells matching with their own siblings. Only about 30% of people who need a transplant can find an HLA-matched donor in their immediate family. For the remaining 70% of patients, HLA-matched bone marrow from other donors is recommended.