Understanding Bone Marrow Transplants: Healing At A Cellular Level

02 September,2024

A healthy and functioning bone marrow is essential for survival. If a person suffers from a disease affecting the bone marrow, it is usually treated through a bone marrow transplant. The first ever successful bone marrow transplant in humans was done in 1968. Ever since then, the range of applications has grown, and it is now used to treat cancer, blood disorders, and many other congenital and acquired diseases. Individuals who wish to donate bone marrow must register as donors. The World Marrow Donor Association (WMDA) has a global database of over 42 million donors.

Over 90,000 bone marrow transplants are conducted worldwide annually. Most of these transplants use the patient's stem cells, whereas some use stem cells from a donor. Countries such as the United States of America, Germany, and India are the leaders in bone marrow transplants.

This blog explores bone marrow transplants in depth, explaining why they are needed, the procedure, and the diseases they treat.

What is a Bone Marrow?

Human bones comprise three parts: compact bone, spongy bone, and bone marrow. The outer layer is made of compact bone, whereas spongy bone is present at the ends of bones. The cavity of some bones, such as the ribs, thigh bones, pelvic bones, vertebrae, and sternum, is filled with a soft, jelly-like material known as bone marrow.

Bone marrow consists of immature cells known as stem cells, which mature and form various types of cells. It can be of two types: red or yellow. The red bone marrow contains blood vessels, fibrous tissue, and blood-forming stem cells, which mature into red blood cells (RBCs), white blood cells (WBCs), and platelets. The yellow bone marrow mainly contains fat and stem cells that form bone, fat, and cartilage.

What is a Bone Marrow Transplant?

Certain disorders, such as cancerous or non-cancerous conditions, blood disorders, or autoimmune diseases, damage the bone marrow, affecting the production of healthy, mature blood cells. In such situations, the patient must undergo a bone marrow transplant. A bone marrow transplant is a systemic procedure of replacing abnormal, damaged, or diseased stem cells with healthy ones. It is also known as a stem cell transplant or hematopoietic stem cell transplant (HSCT).

Why is a Bone Marrow Transplant Needed?

Stem cells mature to form the essential cellular components of blood. Red blood cells, or RBCs, transport oxygen to the organs. White blood cells are part of the immune system, and platelets are responsible for blood clotting. Damage to the bone marrow can affect all these vital functions. Therefore, replacing a dysfunctional bone marrow with a healthy one is essential.

There are several situations where a bone marrow transplant may be necessary, including:

• Conditions in which the bone marrow is unable to generate its own stem cells and needs to be replaced with healthy bone marrow
• After treatment of malignancies, where bone marrow is destroyed due to chemotherapy or radiation therapy and needs replacement to function correctly
• To redevelop the new immune system to destroy cancer cells left behind after chemotherapy or radiation therapy.
• To add new stem cells that will find and destroy cancer cells directly
• In genetic conditions, where the existing bone marrow needs to be replaced by a genetically healthy bone marrow to prevent further degeneration

What are the Different Types of Bone Marrow Transplant?

For a bone marrow transplant, stem cells have to be harvested from the donor and injected into the patient. Based on the type of donor, bone marrow transplant is mainly of two types:

Autologous Bone Marrow Transplant

• For an autologous transplant, stem cells are harvested from the patient's bone marrow.
• These cells are frozen and stored while the patient undergoes cancer treatment, including high chemotherapy or radiation therapy doses, which may destroy the existing bone marrow.
• Once treatment is complete, the cells are introduced back into the bloodstream to regenerate and form new cells.
• An autologous transplant is preferred when patients have healthy stem cells before treatment.
• This process is also known as a rescue transplant.
• An autologous transplant is most commonly used to treat conditions such as multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma, and plasma cell disorders.

Allogeneic Bone Marrow Transplant

• When a patient's bone marrow fails to produce viable stem cells, bone marrow is obtained from a healthy donor and introduced into the patient's blood. This process is known as allogeneic bone marrow transplant.
• For an allogeneic transplant to be successful, the donor and recipient's human leukocyte antigen (HLA) must be a close match.
• Parents, children, or siblings are usually favorable as donors.
• If a match is not found among family members or acquaintances, donors can be found in national bone marrow registries.
• Allogeneic transplants are most often used to treat cancers like acute lymphocytic leukemia, acute myeloid leukemia, and several blood disorders, including aplastic anemia, thalassemia, and chronic granulomatosis.

Other types of bone marrow transplants are: 

• Syngeneic Bone Marrow Transplant: When a patient receives healthy stem cells from their identical twin's bone marrow, it is known as a syngeneic bone marrow transplant.
• Umbilical Cord Blood Transplant: Stem cells are harvested from a newborn's umbilical cord at birth. These cells are frozen and preserved until the need for transplantation arises.
• Haploidentical Transplant: For a haploidentical transplant, the donor need not be a complete match with the patient. A partial match is considered optimal. Biological parents and children are always a half-match for each other, whereas biological siblings have a 50% chance of being a half-match.

How are Donors and Recipients Matched for a Bone Marrow Transplant?

A patient who requires an allogeneic transplant must find a suitable bone marrow donor. It can be someone related to the patient or registered as a donor from a registry.

• The key to finding a donor match lies with the human leukocyte antigen (HLA). HLAs play a crucial part in regulating the body's immune system.
• There are various types of HLAs. However, only a few major ones determine the body's immune response.
• When donor stem cells are required for transplant, the recipient's HLAs are compared with donor HLAs to find the closest match. This process is called HLA typing.
• Finding a close match is essential for the success of the transplant and the prevention of complications.

How are Stem Cells Taken from the Donor?

For an allogeneic or autologous transplant, stem cells are taken from the donor by one of two methods:

• Bone Marrow Harvesting: In this method, the donor is put under general anesthesia, and the stem cells are taken from the bone marrow of the hip bones. The procedure is equivalent to minor surgery and is performed in an operating theatre. It may last an hour or two, and the donor can be discharged on the day of the procedure or the next day.
• Apheresis: This method involves taking cells directly from the donor's bloodstream, known as peripheral blood stem cells (PBSC). A week before the procedure, the donor is injected with filgrastim, a medicine that boosts the production of stem cells and mobilizes them from the bone marrow into the bloodstream. Blood is removed from the donor's body using an intravenous line, passed through a machine to separate the stem cells, and the residual blood is returned to the body. 

What is the Process for a Bone Marrow Transplant?

A typical bone marrow transplant procedure entails pretransplant tests, conditioning, transplant, and engraftment.

Pretransplant Tests

• Before getting a bone marrow transplant, the doctor orders a series of tests and procedures to determine the patient's overall health. These include a complete blood count (CBC), electrocardiogram (ECG), CT scan, liver function test, kidney function test, and others. 
• Once the patient is deemed fit for a transplant, a tube, known as a central venous catheter, is inserted into a vein in the patient's chest, neck, or arm. This catheter is used to withdraw blood and inject medication.

Conditioning

• Conditioning is the process where the patient receives a high dose of chemotherapy, radiation, or both before the transplant. 
• The objective of conditioning is to prepare the recipient's bone marrow for the formation of new cells and to temporarily suppress the immune system so that it does not attack the new cells. In cancer patients, conditioning also helps to kill cancer cells in the body. 
• The type of conditioning required is decided based on the disease being treated, the patient's health, and the type of transplant. 
• Conditioning may cause some side effects, including nausea, vomiting, mouth sores, ulcers, hair loss, fertility problems, infection, and organ complications.

Bone Marrow Transplant

• Once conditioning is complete, stem cells are introduced into the recipient's bloodstream via the central venous catheter on the day of the transplant.
• Unlike bone marrow harvesting, a transplant is not a surgical procedure, but it resembles a simple blood transfusion. The patient is not under general anesthesia for the procedure.

Engraftment

• After the transplant, the newly injected stem cells enter the recipient's bloodstream and reach the bone marrow. 
• These cells mature and form red blood cells, white blood cells, and platelets. This process is termed engraftment.
• Engraftment usually takes place over a few weeks or longer.

What is the Recovery Process After a Bone Marrow Transplant?

After the bone marrow transplant is completed, the recipient is kept under observation at the hospital. The duration of stay will depend upon the type of transplant and severity of complications.

• The doctor will monitor the patient for complications and side effects such as nausea and diarrhea. 
• Frequent blood tests and other tests will be required to assess the situation.
• The conditioning process weakens the immune system, making the recipient more prone to infections. The doctor may prescribe antiviral, antibiotic, and antiviral drugs to prevent these.
• The patient may need frequent blood transfusions until the bone marrow can create adequate cells.
• If the patient has received an allogeneic transplant, they will require immunosuppressant drugs to prevent the body from rejecting the donor cells.
• It may take some time for the patient to resume their daily activities. The total recovery time may range from a few months to a year.
• The patient will have to take several precautions regarding their diet and lifestyle for the rest of their life to avoid late complications and ensure the success of the transplant.

What are the Diseases Treated Using a Bone Marrow Transplant?

Bone marrow transplants have wide medical applications and treat over 70 congenital and acquired disorders, including cancers and blood disorders.

• Congenital disorders treated by bone marrow transplant include sickle cell disease, thalassemia, diamond-blackfan anemia, Fanconi anemia, severe combined immunodeficiency (SCID), adrenoleukodystrophy, Hurler syndrome, Sanfilippo syndrome, mucolipidosis, Gaucher disease, and ataxia-telangiectasia.
• Acquired diseases where bone marrow transplant is used for treatment include blood cancers, solid tumors, hematologic disorders, and more. Bone marrow transplant is employed to treat blood cancers, including:
  • Acute myeloid leukemia (AML)
  • Acute lymphoblastic leukemia (ALL)
  • Chronic myelogenous leukemia (CML)
  • Chronic lymphocytic leukemia (CLL)
  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma
  • Multiple myeloma
• Solid tumors that benefit from bone marrow transplants are neuroblastoma, Ewing's sarcoma, desmoplastic small round cell tumor, and choriocarcinoma.
• Bone marrow transplants can treat hematologic disorders, including aplastic anemia, polycythemia vera, essential thrombocytosis, myelofibrosis, paroxysmal nocturnal hemoglobinuria (PNH), and myelodysplasia.
• Other diseases treated with a bone marrow transplant include amyloidosis, radiation poisoning, human T-lymphotropic virus (HTLV) infection, acquired immunodeficiency syndrome (AIDS), and multiple sclerosis.

What are the Risks Involved With a Bone Marrow Transplant?

A bone marrow transplant can cause several complications, ranging from mild to life-threatening. 

• Some common risks and complications of a bone marrow transplant are infections, painful mouth sores, gastrointestinal irritation, skin rash, diarrhea, and cataracts.
• Bone marrow transplant lowers blood cell count, leading to thrombocytopenia and anemia. A lack of platelets also affects blood clotting, resulting in bleeding in the brain, gastrointestinal tract, lungs, etc.
• Infertility, respiratory issues, muscle spasms, and organ damage are also side effects of bone marrow transplants.
• Patients of bone marrow transplants become increasingly susceptible to new cancers.
• If the body does not accept the new cells, graft failure will occur.
• Graft-vs-host disease (GVHD) is a severe complication seen primarily after allogeneic transplants. In this condition, the donor cells identify the host cells as foreign entities and attack them.

What is the Prognosis for a Bone Marrow Transplant?

The outcome of a bone marrow transplant, or BMT, depends on multiple factors, including the patient's age, overall health, presence of comorbidities, and response to the treatment. It also depends on the type and severity of the disease, the type of bone marrow transplant used, and donor matching. Infection control, post-transplant care, diet, and lifestyle modifications also significantly contribute to the success of the treatment.

As a result, the prognosis of a bone marrow transplant varies from patient to patient. However, as medical science advances rapidly and new techniques are being developed, the chances of a successful bone marrow transplant increase.

Takeaway

A bone marrow transplant is a ray of hope for patients with cancers or blood disorders. However, it is a complex procedure associated with significant risk, and therefore, it requires a high level of medical expertise to succeed. With modern technology and advanced treatment procedures, bone marrow transplants will see broader applications and higher survival rates, with minimized post-transplant complications and improved quality of life.