Advances in bone marrow transplant and cellular therapy

Mayo Clinic Q&A

Mayo Clinic performed its first bone marrow transplant in 1963 and today hundreds of people receive blood and marrow transplants every year at Mayo Clinic in Arizona, Florida and Minnesota. Recently, Mayo Clinic in Rochester, Minnesota celebrated its 10,000th blood and marrow transplant.

Bone marrow transplant is used to treat blood cancers and related disorders by infusing healthy blood-forming stem cells into your body to replace unhealthy bone marrow. A bone marrow transplant is also called a stem cell transplant. Bone marrow transplants may use cells from your own body, called autologous transplant, or from a donor, known as allogeneic transplant.

Autologous stem cell transplants are typically used in people who are producing enough bone marrow but need to undergo high doses of chemotherapy and radiation to cure their disease. These treatments are likely to damage the bone marrow. Prior to treatment, healthy bone marrow cells are collected, frozen and stored for later use. After treatment, the stem cells are infused back into the patient to repopulate the bone marrow.

Allogeneic bone marrow transplant is used when there is underlying bone marrow failure syndrome or for certain types of bone cancers and blood cancers. In those cases, donor bone marrow is needed to replace the diseased bone marrow.

One common complication of allogenic transplant is developing graft versus host disease. This condition occurs when the donor stem cells see the body's tissues and organs as something foreign and attack them. Researchers have now discovered metabolic markers that can predict a person's risk for developing severe graft versus host disease, allowing for a more personalized treatment approach.

"Graft versus host disease occurs in patients that have had an allogeneic transplant from a donor," explains Dr. William Hogan, director of the Mayo Clinic Blood and Bone Marrow Transplant Program in Minnesota. "And this is where the donor immune system doesn't just recognize the leukemia that we're trying to treat — which is what we want — but it also attacks the patient's normal tissues. This can be anything from a relatively mild to a very devastating problem that can occur after transplant. And one of the challenges was that, by the time that has been fully developed, then it's harder to treat. So one of the goals of research in the last few years has been to develop markers that will tell us which patients are at risk of having the most severe graft versus host disease, and allowing us to target more effective treatment toward those patients."

Other recent advances in blood and bone marrow transplant include the use of mismatched donors and the ability to use bone marrow transplant in older, more frail patients thanks to improvements in antibiotics, antifungal drugs and other medications.

Another cellular therapy that is helping treat blood disorders and cancers is chimeric antigen receptor-T cell (CAR-T) therapy. CAR-T involves taking the T cells from a person and reengineering them to recognize and destroy cancer cells.

"CAR-T therapy is a very interesting therapy," says Dr. Hogan. "It's really come to fruition in the last five to 10 years. This is similar to bone marrow transplant, but not quite the same. It's a cellular-based therapy, so not a drug, but using cells that are modified in order to try and treat leukemias and other cancers. And basically, what it does is it takes our native immune system — and then the T cells specifically — and modifies them so that they are much more effective at recognizing targets that are on leukemia cells or other malignant cells. And that really kind of allows us to use the native immune system in a much more effective way of trying to kill leukemias."

Dr. Hogan says CAR-T therapy also is being developed for noncancerous conditions, like aplastic anemia, and research is looking at CAR-T as a treatment for a particular form of inflammatory multiple sclerosis.

"Things have really been transformed over the last five to 10 years with the advent of CAR-T therapy which has been groundbreaking," says Dr. Hogan. "The field of blood and bone marrow transplant continues to move forward, creating more effective treatments with less toxicity for many patients."

On the Mayo Clinic Q&A podcast, Dr. Hogan discusses advances in bone marrow transplant and cellular therapy, including CAR-T.