How Do Bone Marrow Transplants Work?
As per the National Marrow Donor Program, thousands of people with blood cancers like leukemia, multiple myeloma cancer, lymphoma, sickle cell anemia and other life-threatening diseases, depend on a bone marrow or cord blood transplant (also called a BMT) to save their life. This treatment option is an important tool in the arsenal against cancer.
When bone marrow is damaged by disease or does not produce enough healthy blood cells, as in the case with acute myeloid leukemia, a bone marrow transplant may be an option. A bone marrow transplant is a surgical procedure that injects healthy blood producing cells into your body to replace the weak or damaged cells within the bone marrow. Bone marrow is the soft, spongy tissue in the body that is responsible for producing hematopoietic (blood-producing) stem cells.
Bone marrow transplants are often performed to treat certain types of cancers including leukemia, myeloma and lymphoma, but can also be used to treat any immune system diseases that affect the bone marrow or blood by replacing diseased cells with healthy transplanted cells.
Blood is the life-giving fluid that flows through our body’s arteries, veins and capillaries to deliver nourishment, oxygen, electrolytes, hormones, vitamins, antibodies and heat to all of our vital organs. Blood cells are produced in the bone marrow and begin as a stem cell. These stem cells are the first phase of the development of blood cells. As they evolve the 3 types of blood cells are produced. Immature blood cells are referred to as blasts. Thus, when a disease adversely affects the production of blood vessels, debilitating symptoms are the result. Blood plasma contains 3 major parts:
Red blood cells: These are responsible for carrying oxygen from the lungs to the rest of the body. Red blood cells are vital to keeping the body healthy.
White blood cells: Sometimes referred to as leukocytes, these important cells help the body to fight infections and aid the immune system.
Platelets: These cells are responsible for controlling bleeding.
What is a stem cell transplant?
Healthy marrow and blood cells are needed to live. When disease affects marrow so that it cannot function properly, a marrow or cord blood transplant could be the best treatment option, and for some patients, offers the only potential cure.
A bone marrow transplant takes a donor’s healthy blood-forming cells and puts them into the patient’s bloodstream, where they begin to grow and make healthy red blood cells, white blood cells and platelets. Patients receive high doses of chemotherapy to prepare their body for the transplant. Then on transplant day, the patient receives the donated cells in a process that is like getting blood or medicine through an intravenous (IV) catheter, or tube
The terms stem cell transplant and bone marrow transplant are often used synonymously. Typically a patient will undergo chemotherapy to kill any diseased stem cells or malfunctioning bone marrow within their body. This initial step of the bone marrow transplant process is called conditioning, in which existing bone marrow cells, including some leukemia cells, are destroyed. Conditioning allows the donor’s stem cells to take hold in the patient’s bone marrow, kill the remaining leukemia cells, and replaces unhealthy bone marrow and blood cells with healthy marrow and cells.
After the chemotherapy procedure, doctors place healthy stem cells back into your bloodstream. The stem cells slowly make their way to the bone marrow through the blood vessels. Once they enter the bone marrow, the stem cells can aid in the production of new, healthy blood cells.
What makes a Stem Cell Donor a Match?
A person’s tissue type is different from a person’s blood type. Important research in the field of bone marrow transplantation has identified a protein found on the surface of most human cells that make up a person’s tissue type. Human leukocyte antigen (HLA) is this protein that helps the immune system identify the difference in the body’s own body tissue and invading cells. Matching HLA is the key to a successful bone marrow transplant. There are 6 known major HLA antigens and a bone marrow transplant patient is considered a match to a donor when all 6 of those antigens align. For some bone marrow and peripheral blood stem cell transplants a match of 5 out of 6 antigens is sometimes used.
Types of Bone Marrow Transplants / Stem Cell Transplants
Bone marrow transfers might utilize cells from your own body (autologous transfer) or from a stem cell donor (allogeneic transfer).
Autologous Stem Cell Transplant
In an autologous stem cell transplant the patient is able to donate stem cells from their own body. Stem cells are taken from the patient, frozen, treated and then implanted back in the patient. The procedure to collect the stem cells is called apheresis. Before apheresis is performed, you will receive a growth factor that will help the body produce stem cells and move the stem cells into the bloodstream for easier collection. The procedure entails blood being drawn out of the body and circulated through a machine that separates the blood into the different parts. Stem cells are collected from these separated blood cells and frozen. The remaining blood is transplanted back into the body.
Allogeneic Bone Marrow Transplant
Allogeneic bone marrow transplants use stem cells from a donor. The donor can be related or unrelated but must share a similar genetic makeup with the patient. Patients typically undergo myeloablative therapy in which high doses of chemotherapy are used to kill unhealthy stem and bone marrow cells. The donor stem cells that were previously collected and frozen are then thawed and transplanted into the patient’s body. The donated stem cells are cancer free and some donors can even be asked to donate more stem cells or white blood cells as needed by the recipient.
Graft rejection occurs when the patient’s body sees the implanted cells from the stem cell transplant as invaders and the immune system tries to reject or destroy the cells. Graft rejection is rare when the donor and recipient are close genetic matches, which is why this is such an important step in ensuring a bone marrow transplant works.
Haploid-Identical Match Transplant
Bone marrow donors can sometimes be a parent or sibling of the patient. Stem cell transplants require that the donor and recipient have tissues that are a close genetic match. The benefit of this type of transplant is that the donor shares at least half of the genes of the patient. The chance that the 6 HLA antigens will align with a sibling is 1 in 4. Typically the search for a likely donor starts with parents and siblings. If a good match is not found in that initial investigation, then the search will continue with other relatives and then finally to the general public.
Umbilical Cord Blood Transplant
An umbilical cord connects a baby to their mother. Once the baby is born, they no longer need the umbilical cord. Stem cells from the umbilical cord can be used in this type of transplant. The benefit of this type of bone marrow transplant is that the stem cells from the umbilical cord develop and reproduce into mature, fully functioning blood cells much more quickly than those donated from another adult. Transplants that utilize cord blood stem cells can be used for both children and adults.
A matched unrelated donor (MUD) transplant is typically found through a national registry when a relative that is a close match is unavailable. Since there are thousands of different HLA combinations, these national registries make it possible to catalog and search for the exact HLA match among registered donors.
What Can You Expect with your Bone Marrow Transplantation
A bone marrow transplant is a serious surgery that can take a year or longer to recover from. Every person’s experience will be different but being prepared for the steps of the transplant will be beneficial to both patients and caregivers.
Before your Bone Marrow Transplant
A team of healthcare professionals are assembled to ensure a successful transplant. Doctors on the care team will run a variety of tests before the bone marrow transplant to assess your overall general health, blood and organ health. Basic blood tests to assess the red blood cells, white blood cells and platelet health will be used, as well as more comprehensive testing to examine the strength of your organs and gather information about your general health. Common tests include:
- An EKG or other heart evaluation to determine information about the health or your heart and how your heart pumps
- A pulmonary function test to examine your lungs
- A urine collection to check for creatine and evaluate the health of the kidneys.
- A liver evaluation
- CT scans, PET scans, skeletal surveys, or a bone marrow aspiration may be performed to check the extent of the disease and discern vital information about the recipient’s health.
- A bone marrow biopsy that examines both the liquid and spongy part of the bone marrow for disease.
These tests are designed to make sure you, the patient, are physically ready to receive the bone marrow transplant before the procedure to transplant stem cells is ever begun. Typically, all other treatment options and the risks associated with each treatment are discussed before starting the transplant process.
Several days before the bone marrow transplant, a central venous catheter is put into a vein in the recipient’s chest. This tube will be used by the team of medical professionals to take blood and give medicine. The tube stays in place until after the transplant of the stem cells is completed. Typically, the patient receives drugs to induce drowsiness before the catheter is placed. You should not feel the procedure.
For allogeneic bone marrow transplants, a matching donor must be found as part of this preparatory process. Donors can be pulled from family members that have matching HLAs, or from a bank of registered donors if a transplant match is not found within the family.
In an allogenic transplant, the bone marrow donor will get daily shots of growth factor to help increase their white blood cell count before the collection process of the stem cells begins. Growth factor shots are given subcutaneously into parts of the body that typically have a layer of fat, like the stomach, or backs of the arms or thighs.
In an autologous transplant, the patient would begin getting those growth factor shots several days or weeks before the transplant, so that the patient’s body would produce an abundance of white blood cells. The stem cells are then collected before the transplant procedure can begin. Growth factor can also help after transplantation by encouraging engraftment.
As part of the collection process, the stem cell transplants are processed in a lab to purify and concentrate the collected stem cells. The cells are then frozen for preservation in a process called cryopreservation. The stem cell transplants will be thawed as the final preparation before being introduced (or re-introduced) to the patient’s body.
Before the transplant, patients are typically given a high dose of chemotherapy over a 5-10 day window to prepare their body to receive the transplanted cells. This helps to kill off the diseased marrow cells and allow room for the transplanted cells to grow.
During your Stem Cell Transplant
The stem cell infusion takes around 30 minutes to an hour per dose. The stem cells are typically infused into the body’s bloodstream through the catheter. The stem cells will find their way into the bone marrow and begin to create new healthy cells. This is called engraftment and usually takes several weeks. This is an important milestone in the transplant journey.
The transplant process can create a sudden taste and smell in your mouth if a drug called DMSO (Dimethyl Sulfoxide) is used as part of the thawing process. Hard candy can usually take the taste sensation away. The DMSO helps the stem cells stay whole as they are thawed.
After your Bone Marrow Transplant
After the bone marrow transplant, patients typically remain in the hospital for three to four weeks as the bone marrow recovers so that they can be closely monitored. Some patients will need to stay in or near the hospital for longer. If a complication arises, a patient will stay in the hospital longer. Patients will need transfusions containing blood cells and platelets as part of the recovery process, and will undergo daily testing to monitor them.
Typically patients see their white blood cell count increase, then the red blood cell count, and finally the platelets. Blood counts begin coming back to normal 10 to 20 days post transplant. As blood count returns to normal the risk of complications begins to decrease and the antibiotics and transfusions will decrease.
For allogeneic bone marrow transplants, medications to reduce the risk of graft-versus-host-disease and to suppress the immune system are often prescribed. In addition, because it takes time for the immune system to recover from a transplant, other medications to help prevent infection are commonly prescribed.
A healthy lifestyle that incorporates a healthy-eating plan, and promotes regular physical activity to help strengthen bones will be part of the recovery process and long term care. A healthy lifestyle may help to reduce the need for other treatments and may help control other common AML symptoms like nausea.
Common Complications of a Bone Marrow Transplant
There are many complications that can arise depending on the type of bone marrow transplant being performed, the patient’s age and overall health and the variance of tissue match between the donor and recipient. Common physical complications of a bone marrow transplant include:
Infection: While bacterial infections are the most common type of infection, any type of infection can be dangerous for a recent bone marrow transplant patient. A strict regimen to monitor the central venous line is important. Mouth sores are another common source of post chemotherapy infection, and thus a strict oral care regimen must be followed.
Nausea and vomiting: The administration of drugs to help combat nausea and vomiting are important to your post transplant care.
Hair loss: Most people experience hair loss following the high dose chemotherapy used to prepare your body for the transplant.
Loss of Appetite: Altered taste sensations can often lead to a loss of appetite post transplant. A healthy diet and plenty of fluids is essential to your self-care.
Tiredness: Even simple tasks like walking or bathing, can create tiredness in many patients after chemotherapy. This gets better with time and healing.
Emotional Issues: As with any major surgery or diagnosis, a bone marrow transplant can cause emotional distress. Common emotions of both patients and their caregivers can include feeling overwhelmed, fear of the unknown, guilt over not being one’s self, depression or sadness.
Graft Versus Host Disease: GVHD is when the patient’s immune system sees the donor’s stem cells as different and begins to attack the cells instead of incorporating them into the patient’s own bone marrow. Immunosuppressant drugs are often given as a precautionary measure against GVHD. Many patients will have some symptoms of GVHD after a bone marrow transplant, and symptoms can range from mild to severe.
If you experience any of the following symptoms during your hospital stay or after leaving, you should call the doctor or make an appointment with your health care professional:
- Fever of greater than or equal to 100.5° F
- Any bleeding, even small amounts
- Central line problems or indications of infections like redness, swelling or pain.
- Shortness of breath or difficulty breathing
- Vomiting or diarrhea
- Chills or sweating
- Increase in pain
How Does Bone Marrow Transplant for AML Work?
BMT, also known as a bone marrow transplant or blood stem cell transplant, can treat patients who have AML, including older patients. The transplanted tissue replaces the unhealthy blood-forming cells (stem cells) in the marrow with healthy ones. For some people, a stem cell transplantation can cure their disease.
The most common type of bone marrow transplant for AML is an allogeneic stem cell transplant. This type of transplant uses healthy blood-forming cells donated by someone else to replace the unhealthy ones. These healthy transplant cells can come from a family member, unrelated donor or umbilical cord blood. First, you get chemotherapy (chemo), with or without radiation, to kill the unhealthy cells. Then, the healthy cells are given to you through an intravenous (IV) catheter. After the transplant, the new cells travel to the inside of your bones and begin to make healthy blood cells.
The entire stem cell transplantation process, from when you start chemo or radiation, until hospital discharge, can last weeks to months. This is followed by many months of recovery near the transplant center and at home. Your stem cell transplant team will watch you closely to prevent and treat any side effects or complications.
The SIERRA Trial and AML Bone Marrow Transplant
The SIERRA clinical trial seeks to determine the effectiveness of the investigational drug Iomab-B, which may enable more transplants in patients aged 55 and older. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, in a potentially safer and more efficacious manner than intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning.
The SIERRA clinical trial may help improve the way AML is treated in the future.
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