Bone marrow transplantation (BMT) and cancer

ALSO KNOWN AS: Peripheral blood stem cell transplantation (PBSCT)

DEFINITION: Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures used in cancer therapy to provide stem cells to a patient to replace those lost to disease, chemotherapy, and radiation. Stem cells are obtained from patients themselves, a related or unrelated donor, or umbilical cord blood taken after the birth of a baby. Autologous transplants use the patient’s stem cells. Allogeneic transplants use stem cells from a related person; the donor is most often a parent or sibling, but an unrelated but matched donor or umbilical cord blood may be used. A syngeneic transplant is done with stem cells from an identical twin.

Cancers treated: Leukemia, lymphoma, multiple myeloma, aplastic anemia, and neuroblastoma; additional cancers eligible for transplant are being evaluated in clinical trials.

Why performed: Cancer patients are often treated with high doses of chemotherapy and radiation to rid the body of cancer cells. Chemotherapy and radiation therapy target rapidly dividing cells in the body. Because cancer cells and stem cells divide quickly, the therapy may kill them both. BMT and PBSCT rescue patients after high-dose chemotherapy and radiation by replacing destroyed stem cells with healthy stem cells. Transplanted stem cells allow the bone marrow to produce the blood cells the body needs. Additionally, white blood cells from the donor will identify any remaining cancer cells in the patient’s body and attack them as foreign, thus providing additional cancer cell kill. This graft-versus-tumor (GVT) effect—in this case, stem cells versus cancer cells—is essential in some kinds of leukemia treated with allogeneic transplants and enhances the effectiveness of the transplant.

To understand bone marrow transplantation, it is important to understand the role of stem cells. Stem cells are found in the bone marrow and can develop into different types of cells in the body, such as blood cells. Blood cells initially begin as immature cells, called hematopoietic stem cells, constantly and rapidly dividing. Stem cells used in transplantation are not embryonic stem cells used in cloning experimentation. Mature stem cells are available to the body in the bone marrow, but some stem cells circulate in the bloodstream and are called peripheral blood stem cells. The role of stem cells in the body is to fight infection (stem cells that evolve into white blood cells), carry oxygen (stem cells that evolve into red blood cells), and prevent bleeding (stem cells that develop into platelets).

Patient preparation: The first step in the transplant procedure is determining the type of transplant that will be used by determining if the patient has a potential donor. Doctors try to minimize side effects by using stem cells that match the patient’s stem cells as closely as possible. Different proteins on the cell surface, called human leukocyte antigens (HLAs), are identified with a blood test. The success of the transplant depends on how close a match can be made between the donor stem cells and the patient’s stem cells. Close relatives are the most likely sources of matching stem cells, but less than one-third of patients will have a matched sibling. Finding an unrelated, matched donor is possible in about one-half of cases, and the chance of a match increases if the donor and patient are of the same ethnic and racial background. If a potential donor is identified, then blood work will be used to determine the level of the match. A donor registry may also be used to identify donors who have offered to provide stem cells for transplantation if they match a patient in need.

If no donor match can be found, the patient's stem cells may be used in an autologous transplant. Stem cells are obtained from the patient and then treated to remove cancer cells. Extra stem cells are removed from the patient, as some healthy cells may be damaged when the cancer cells are removed.

Once the type of transplant is determined, the stem cells are obtained or harvested. The bone's liquid center is the stem cell source used in BMT. The donor is given anesthesia to make the harvesting procedure pain-free. General anesthesia or regional anesthesia, which numbs the area below the waist, is used. Large needles are inserted into the hip (pelvic) bone or, rarely, the breastbone (sternum), and marrow is drawn out. The harvesting procedure takes approximately one hour. The bone marrow is then treated to remove blood and bone fragments, frozen with a preservative if not to be used immediately, and stored until it is time to administer the stem cells to the patient. Stem cells that are frozen (cryopreserved) can be stored for many years.

If the doctor determines that a peripheral blood stem cell transplant is the best choice for the patient, stem cells are harvested from the bloodstream rather than the bone marrow. Autologous transplants often use peripheral blood stem cells (PBSCs). Apheresis removes PBSCs with a machine that removes the stem cells and then returns the remainder of the blood, minus the stem cells, to the donor. Medicine that stimulates the growth of stem cells in the body may be given to the donor for several days before the harvest. Apheresis may take up to six hours. The cells are processed and frozen for future use.

Umbilical cord blood may also be a source of stem cells for transplantation. The mother requests that cells be harvested when the birth occurs. Cord blood banks may store the cells for potential use by the family later or may be given to a public cord blood bank for use by any matching patient. Blood is taken from the umbilical cord and placenta and then frozen for storage. Since only a tiny amount of blood may be available, cord blood transplants are usually most effective in children or small adults.

Steps of the procedure: The patient usually receives high-dose chemotherapy (anticancer drugs) and radiation to rid the body of as many cancer cells as possible. Depending on the hospital program, the patient may be admitted or undergo the preoperative regimen as an outpatient. Once the regimen before the transplant is complete, the patient is ready to have the procedure. The stem cells are thawed and given through an intravenous line, as in a blood transfusion. The infusion of the stem cells may take from one to five hours.

After the procedure: Once the infusion of the stem cells is complete, the wait begins for the cells to graft (or take) and produce new blood cells for the patients. During this time, the patient may be in a room with special air filters and strict infection control guidelines. Because the patient has very few stem cells until the graft occurs, the body cannot fight infection or control bleeding. The wait for engraftment ranges from two to six weeks. High fevers, chills, shortness of breath, coughing, low blood pressure, and weakness may occur. With allogeneic transplants, the most significant complication that arises is graft-versus-host disease.

Once discharge from the hospital occurs, the patient may face various problems. Fatigue, physical lingering issues after the transplant, and psychological problems may arise. Frequent visits to the physician to follow progress after the transplantation and to manage symptoms are expected. The recovery period may be a year in length.

Risks: There is minimal risk involved with donating bone marrow or undergoing apheresis. If the match between donor and patient is incomplete, graft rejection may occur in rare instances. The most significant risk with an allogeneic transplant is graft-versus-host disease. Patients may be unable to have children after a transplant, and this topic should be discussed with the physician before the transplant.

Results: Survival rates after transplantation vary by disease, type of transplant, and the patient's age. Survival rates after transplantation vary by disease, type of transplant, and the patient's age. In 2021, Medical News Today cited a study by the Canadian Cancer Society stating that 65-70% of bone marrow patients under 60 will experience complete remission. This therapy, however, will be significantly less effective for those above this age. The three-year survival rate for this group is 25-40%.

Bibliography

""Bone Marrow Transplant." Mayo Clinic, 28 Mar. 2024, www.hopkinsmedicine.org/health/treatment-tests-and-therapies/bone-marrow-transplantation. Accessed 8 July 2024.

"Bone Marrow Transplantation." Johns Hopkins Medicine, 2024, www.hopkinsmedicine.org/health/treatment-tests-and-therapies/bone-marrow-transplantation. Accessed 8 July 2024.

Eisenberg, Seth. "The Changing Face of Bone Marrow Transplant." ONS Connect, vol. 27, no. 11, 2012, pp. 10–14.

Jenks Kettmann, J. D., and E. M. Altmaier. “Social Support and Depression among Bone Marrow Transplant Patients.” Journal of Health Psychology, vol. 13, 2008, pp. 39–46.

"How Stem Cell and Bone Marrow Transplants Are Used to Treat Cancer." American Cancer Society, 20 Mar. 2020, www.cancer.org/cancer/managing-cancer/treatment-types/stem-cell-transplant/why-stem-cell-transplants-are-used.html. Accessed 8 July 2024.

Kioussi, Chrissa. Stem Cells and Tissue Repair: Methods and Protocols. New York, Humana, 2014.

Nadir, Y., and B. Brenner. “Hemorrhagic and Thrombotic Complications in Bone Marrow Transplant Recipients.” Thrombosis Research 120, vol. 2, 2007, pp. 92–98.

Reisner, Yair, and M. F. Martelli. Bone Marrow Transplantation across Major Genetic Barriers. Hackensack, World Scientific, 2010.

Rishe, Jenneh. "What to Know about Bone Marrow Transplants for AML." Medical News Today, 20 Oct. 2021, www.medicalnewstoday.com/articles/aml-bone-marrow-transplant. Accessed 8 July 2024.