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26th October 2022

Bone Marrow Transplants Advance as Procedure Hits Historical Milestone

Over several decades, blood and bone marrow transplants have become standard therapy for diseases affecting the blood, such as cancers, anaemia, and leukaemia. Several advances have been recorded in the interim between the first blood and marrow transplant in the 20th century and today, making these transplants more useful and safer. 

MAYO CLINIC CELEBRATES ITS 10,000TH BLOOD AND MARROW TRANSPLANT

In 1963, Dr Robert Kyle, a doctor at Mayo Clinic in Rochester, recommended an experimental procedure to Nancy McLain, then a young girl. In 1960, McLain had been diagnosed with a rare blood condition known as aplastic anaemia, where the bone marrow cannot produce enough red blood cells, white blood cells, and platelets. Over three years, she had received 98 pints of blood, received her last rites twice, and lost much of her energy. She consented to the procedure suggested by Dr Kyle, receiving a transplant from her twin sister’s bone marrow. In a few weeks, her body had regained the ability to produce blood cells once more, and her blood returned to normal. 

McLain’s transplant was pioneering, representing the first of many such transplants to help patients affected by blood diseases. Today, she’s a grandma and was present at the anniversary of the 10,000th blood and bone marrow transplant at Mayo Clinic in Rochester, Minnesota. Mayo Clinic now performs hundreds of bone marrow transplants on patients worldwide, giving them an opportunity for a new life. 

To celebrate the milestone at Mayo, the current team of doctors and nurses in Mayo’s blood and bone marrow transplant program received a visit from Dr Kyle, Nancy, and her twin sister, Engesmoe. Dr Kyle, now 98. A heartwarming reunion, it was an opportunity for everyone to appreciate the journey in blood therapy so far. Dr William Hogan, the current director of the Mayo blood and bone marrow program, noted just as much, thanking the pioneering trio for taking the first bold steps. 

Blood and bone marrow transplantation

A blood and bone marrow transplant, also known as a haematopoietic stem cell transplant, is a procedure where a patient receives an infusion of healthy, blood-forming stem cells to replace unhealthy bone marrow cells. Haematopoietic stem cells are bone marrow cells that develop into healthy red blood cells, white blood cells, and platelets. When they cannot do this, such cells are said to be diseased, leading to symptoms of anaemia. 

There are many reasons a person’s bone marrow cells might stop working properly, including genetic and non-genetic. For example, high-dose chemotherapy or radiation can destroy the genetic material of bone marrow cells, making them aplastic or unable to reproduce. Likewise, diseases such as aplastic anaemia, multiple myeloma, leukaemias, and lymphomas can severely compromise the body’s ability to produce healthy blood cells. 

If a patient faces these conditions, the doctor will carry out some tests to assess the general health status of that patient. Not all patients require a blood and marrow transplant, which is why these tests are important. Depending on the results of the tests, the doctor may then recommend a transplant. There are two major types of blood and marrow transplant that a patient may receive, which will depend on the nature of the person’s condition:

Autologous, or “auto” transplant 

In an autologous transplant, the stem cells for the transplant come from your own body. This procedure is also called “stem cell rescue”. Here’s how it works: before high-intensity radiation therapy or chemotherapy, the patient’s doctor extracts some of the patient’s hematopoietic stem cells and stores them in-vitro. After the therapy, the doctor returns the stem cells to the patient’s bone marrow. 

Allogeneic or “allo” transplant 

In the allogeneic procedure, the stem cells come from a different person, called a donor. Stem cells are extracted from the donor’s bone marrow and infused into the patient’s bone marrow. For an allogenic transplant to work, the donor and recipient’s blood types must closely match. Hence, typical donors are siblings, parents, or close family members. 

A blood and marrow transplant is one of the most effective procedures for treating patients with blood diseases, with a 70 percent – 90 percent survival rate for patients with non-malignant disease and up to 68 percent in patients with acute leukaemia. However, it is important to note that a few complications or side effects can arise during the procedure. These include pain, infections, graft failure, and graft-versus-host disease. Side effects will differ depending on the patient’s condition, tissue transplanted, and other factors. However, medicine is advancing rapidly to provide new solutions to make blood and marrow transplants safer and more effective. 

Modern medicine is making promising advances to improve blood and marrow transplants for patients. Here are a few of them: 

Use of mismatched donors 

One of the most dangerous complications of blood and marrow transplants from a donor is the rejection of the donor’s stem cells. This typically leads to graft failure, or graft-versus-host disease, in which the donated stem cells attack the host’s tissue. To prevent this, doctors initially had to find the closest match possible, such as an identical twin. However, new advances have made it possible to carry out transplants with imperfectly-matched donors, such as non-twin siblings and other family members. Patients can now receive bone marrow transplants from unrelated donors, provided they meet certain criteria. 

CAR-T cell therapy 

T-cells allow the body to recognize and destroy foreign cells. In a new advancement, T-cells are infused through a procedure known as chimeric antigen receptor-T cell therapy (CAR-T), which involves reengineering the donor’s T-cells to recognize antigens and returning them to the patient. This has helped treat various blood disorders, including leukaemia, lymphomas and multiple myeloma. 

Reduced-intensity conditioning 

The conditioning phase is an important step in a bone marrow transplant. During conditioning, patients receive a high dose of chemotherapy (and sometimes radiation) to prepare the body for the transplant and clear any remaining diseased cells. Many older people are not strong enough for high-intensity conditioning, which has prevented them from receiving marrow transplants in the past. Modern advances have now made it possible for older people to receive bone marrow transplants through a therapy that allows for lower-intensity conditioning. 

Memory T-cell infusion after T-depleted grafts 

For transplant recipients with depleted T-cell counts, the road to recovering full immunity is longer. Usually, the body’s cells have to encounter an antigen before producing antibodies against it. A memory T-cell infusion bridges this by providing the patient with active memory T-cells so that the body is better equipped to handle common infections. A pilot study of this new solution showed an 80 percent and 88 percent survival rate in malignant and non-malignant conditions, respectively. 

Use of bone marrow transplants to treat other conditions 

In recent years, researchers and physicians have been examining the use of bone marrow transplants to treat other conditions. Among the promising conditions are multiple sclerosis and solid tumour cancers. According to a randomized control trial in the UK, 94 percent of patients with relapsing MS didn’t see relapse for at least three years – compared to 40 percent of those on drug treatments. While the possibilities are exciting, more research needs to be done to explore new opportunities for harnessing bone marrow transplants in medicine. 

The potential for advancement in bone marrow transplants is great, promising new opportunities to help patients suffering from cancers and other diseases. To help to bring these possibilities to life, more people need to be inspired to participate, either as donors like McLain, or as researchers and clinicians in cancer immunotherapy like Dr Kyle.

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