Understanding Bone Marrow and Stem Cell Transplantation
Watch the Cancer.Net Video: Bone Marrow and Stem Cell Transplantation: An Introduction, with Sonali Smith, MD [1], adapted from this content.
This is the first article in a two-part series on bone marrow and stem cell transplantation. It provides an overview and explains the differences between autologous and allogeneic transplants. Part II [2] describes side effects of the treatment. ASCO member Edward Agura, MD, Director of the Program in Blood and Marrow Transplant at Baylor University Medical Center in Dallas, Texas, contributed to these articles.
Blood and marrow transplantation is a medical procedure in which diseased marrow (a spongy, fatty tissue found inside larger bones) is destroyed and then replaced with healthy bone marrow from the patient or from a volunteer donor. It is a treatment used most often for leukemia, lymphoma, and multiple myeloma. It may also be used for some genetic diseases that involve the blood.
The purpose of bone marrow and hematopoietic (blood-forming) stem cells
Bone marrow produces more than 20 billion new blood cells every day throughout a person's life. The driving force behind this growth is the hematopoietic stem cell. Hematopoietic stem cells are found in both the blood stream and bone marrow. This specialized cell has the ability to reproduce itself and create the different cell types that make up our blood. These include red blood cells (cells that carry oxygen to all parts of the body), white blood cells (cells that help the body fight infections and diseases), and platelets (cells that help blood clot and help control bleeding). Signals passing from the body to the bone marrow tell the stem cells what cell types are needed most. The essential functions of red blood cells, white blood cells, and platelets are disrupted in patients with bone marrow diseases and certain types of cancer.
Today, a bone marrow transplant is more commonly called a stem cell transplant because it is the blood stem cells that are typically being transplanted, not the actual bone marrow tissue.
Types of stem cell transplantation
There are two main types of transplantation: autologous transplantation (also known as an AUTO) and allogeneic transplantation (also known as an ALLO). A patient undergoing an AUTO transplant receives his or her own stem cells. On the other hand, a patient undergoing an ALLO transplant receives cells from another person. Regardless of the source of the stem cells, a transplant is performed by infusing, or transfusing, the collected stem cells into the patient's vein. The stem cells then remain in the bloodstream for about 24 hours until they find their way to the marrow space, where they grow and multiply, beginning the healing process.
In the AUTO transplant process, the patient's stem cells are collected and then stored in a specialized freezer that can preserve them for decades. Typically, the patient is treated the following week with powerful doses of chemotherapy and/or radiation therapy, after which the frozen stem cells are thawed and transfused back into the patient.
Meanwhile, the first step for an ALLO transplant is to find a donor match. Specific proteins, called human leukocyte antigens (HLA), are found on the surface of white blood cells and throughout the body; the combination of these proteins make each person's tissue unique. HLA typing is a special blood test that identifies these proteins. A successful bone marrow transplant requires the donation of near-perfect, HLA-matched bone marrow. HLA-matched bone marrow/blood stem cells given to a person during transplantation are less likely to result in graft-versus-host disease [2] (GVHD, a complication in which the immune cells in the transplanted bone marrow recognize the recipient's body as foreign and attacks it).
The patient's siblings usually have the best chance of being a complete match. Occasionally, other family members can be a match. Or, an unrelated volunteer donor may be the best match. Learn more about donating bone marrow [3].
During an ALLO transplant, the patient first undergoes treatment similar to that given during an AUTO transplant. However, the stem cell donation is coordinated so that it occurs at the same time as the end of the chemotherapy and/or radiation therapy. The donor stem cells are collected on or near the transplant day, and the patient receives them fresh and unfrozen through an injection into a vein. ALLO transplantation is mainly used for patients with cancerous or badly diseased marrow because AUTO cannot be used for these patients.
Other, investigational types of transplants have been developed to meet the needs of patients who cannot receive ALLO or AUTO transplants and are listed below. These situations include patients who cannot find a perfectly matched sibling or unrelated donor or patients who cannot undergo the rigors of powerful chemotherapy and radiotherapy.
Umbilical cord blood transplantation. For people who cannot find a matched donor, umbilical cord blood transplantation may be an option. Although still a relatively new source of stem cells, cord blood units are used at cancer centers around the world. The results in children have been excellent. In adults, the technology is still underdeveloped, and patients may face additional risks that should be discussed with the doctor. Learn more about donating umbilical cord blood [4].
Mini-transplantation (nonablative or reduced-intensity transplantation). For a mini-transplant, the treatment before transplantation of donor cells is milder, resulting in fewer side effects. For example, there may be no hair loss, fewer blood transfusions, and less time spent in the hospital. Large transplant centers offer this approach for patients who meet specific criteria, such as older patients with slow-growing cancers. However, it may not be as effective for patients with a fast-growing cancer.
Parent/child and haplotype mismatched stem cell transplantation. This rare type of transplantation is not performed by most centers in the United States because of the high complication rate. However, when no matched donors can be easily found, it may be the only option. For this type of transplant, the donor is a family member who is only a 50% match, rather than the desired nearly 100% match. Parents, children, or siblings may be donors. Because of the incomplete match, complicationsâsuch as GVHD, infections, and failure of donor cells to growâhappen much more often than with matched-donor transplantation.
Comparing AUTO and ALLO transplants
ALLO transplants have two advantages over AUTO transplants. First, with an ALLO transplant, the patient receives cancer-free stem cells because they come from a healthy donor. With an AUTO transplant, there is always the risk that the frozen stem cell product will contain some remaining cancer cells.
In addition, with AUTO transplants, the cancer-killing effect ends when the chemotherapy and/or radiation therapy ends. The remainder of the treatment helps patients recover from side effects. In contrast, the ALLO transplant recreates the immune system, which continues to attack any remaining cancer cells after the completion of chemotherapy and/or radiation therapy. This effect (called the graft-versus-tumor effect) is especially strong with some cancers.
However, a patient receiving an ALLO transplant faces tissue rejection risks that an AUTO transplant patient does not.
Choosing between AUTO and ALLO transplants
The choice of transplant depends on many factors, including the type of disease being treated, the health of the patient's own marrow, the extent of bone marrow injury caused by previous chemotherapy, and the age and overall health of the patient.
The decision is complex; it cannot be made without the input of a doctor who specializes in transplant medicine and performs an in-person evaluation of the patient and the potential donor. This means the patient may need to travel to a center [5] that performs many transplantation procedures to talk with a specialist. A patient should consider other nonmedical factors, such as his or her support system, the ability to take time away from work or family, insurance coverage, and access to transportation.
Transplantation timeline
The timing of bone marrow transplantation is often misunderstood. Many patients are surprised to learn that it is a process that takes weeks and months from beginning to end.
The following timelines lay out the major steps for AUTO and ALLO transplants. One phase usually leads directly to the next, but some phases (such as stem cell collection) may be done in advance. Talk with your doctor to learn the specific timeline for your treatment.
AUTO transplant timeline
Phase I: Patient bone marrow/blood stem cell collection
- This involves surgical placement of a transplant catheter (a thin tube temporarily put into a large vein to make injections easier); injections of white blood cell growth factor (medication to increase white blood cell levels, which helps the body fight infections); bone marrow harvest surgery or blood collections through apheresis (the process of giving only select blood components: platelets, plasma, red cells, granulocytes, or a combination of these).
- Overall time: One to two weeks
- Treatment setting: Outpatient (does not require hospital admission; it can take place at a hospital building, a clinic, or a doctor's office)
Phase II: Transplant treatment
- This involves chemotherapy and/or radiation therapy.
- Overall time: Five to seven days
- Treatment setting: Outpatient or inpatient (requires admission to a hospital)
Phase III: Stem cell transfusion/infusion
- This involves transfusion of stem cells by intravenous (IV) injection, which takes about one hour.
- Overall time: One day
- Treatment setting: Outpatient or inpatient
Phase IV: Recovery
- This involves antibiotics, growth factors, blood transfusions, and managing any side effects from the procedure.
- Overall time: Two weeks
- Treatment setting: Outpatient or inpatient
ALLO transplant timeline
Phase I: Donor bone marrow/blood stem cell collection
- This involves injections of white blood cell growth factor and bone marrow harvest surgery or blood collections through apheresis.
- Overall time: One week
- Treatment setting: Outpatient
Phase II: Transplant treatment
- This involves chemotherapy and/or radiation therapy.
- Overall time: Five to seven days
- Treatment setting: Outpatient or inpatient
Phase III: Stem cell transfusion/infusion
- This involves transfusion of stem cells by intravenous (IV) injection, which takes about one hour.
- Overall time: One day
- Treatment setting: Outpatient or inpatient
Phase IV: Recovery
- This involves medicationsâincluding medications that suppress the immune system, antibiotics, and growth factorsâand blood transfusions and fluids for symptom management [2].
- Overall time: Eight to 12 weeks
- Treatment setting: Mostly outpatient, some inpatient
Milestones of successful transplantation
"Success" means different things to different people. The following are common milestones by which success is measured by patients, their families, and doctors.
Milestone 1: Recovery of blood counts to safe levels
Most types of transplantation cause blood counts to fall from normal levels to near zero for a period of one to two weeks. During this time, there is danger of infection from low white blood cell levels, danger of bleeding from low platelet levels, and danger of fatigue from low red blood cell levels. The risks are reduced by using transfusions and antibiotics during this time. The true measure of recovery is the return of blood counts to normal levels through the multiplying of stem cells.
Milestone 2: Cure of the disease
The intent of stem cell transplantation is to cure the disease. For some types of cancer, prolonged remission (time spent without any signs of cancer) is the best result, but for many serious cancers of the marrow, such as acute leukemia and lymphoma, a permanent cure is possible. However, there is no way to know for sure that the cancer is permanently gone, so patients are encouraged to have regular follow-up care and testing to watch for signs that the cancer has come back.
Questions to ask the doctor
Talking often with the doctor [6] is important to make informed decisions about your health care. These suggested questions are a starting point to help you learn more about your cancer care and treatment. You are also encouraged to ask additional questions that are important to you.
- Which type of bone marrow or stem cell transplantation would you recommend? Why?
- Who will be part of my treatment team, and what does each member do?
- Will I receive chemotherapy and/or radiation therapy before the transplantation?
- Can you explain the timeline for treatment?
- How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
- What short-term and long-term side effects may be associated with my cancer treatment?
- Will this treatment affect my ability to become pregnant or have children?
- If I'm worried about managing the costs related to my cancer care, who can help me with these concerns?
- Where can I find emotional support for me and my family?
- Whom do I call for questions or problems?
More Information
Side Effects of Bone Marrow and Stem Cell Transplantation [2]
Finding a Treatment Facility [7]
Additional Resources
National Marrow Donor Program [9]
Blood and Marrow Transplant Information Network [10]
National Bone Marrow Transplant Link [12]
Last Updated: September 11, 2011