Healthy bone marrow and blood cells are needed in order to live. When disease affects bone marrow so that it can no longer function effectively, a marrow or cord blood transplant could be the best treatment option; for some patients it is the only potential cure.
Here are some key points about bone marrow. More detail is in the main article.
- Bone marrow produces 200 billion new red blood cells every day, along with white blood cells and platelets.
- Bone marrow contains mesenchymal and hematopoietic stem cells.
- Around 10,000 people in the US are diagnosed each year with diseases that require bone marrow transplants.
- Several diseases pose a threat to bone marrow and prevent bone marrow from turning stem cells into essential cells.
What is bone marrow?
Bone marrow is soft, gelatinous tissue that fills the medullary cavities, the centers of bones. The two types of bone marrow are red bone marrow, known as myeloid tissue, and yellow bone marrow, or fatty tissue.1
Long bone cross-section showing both red and yellow bone marrow.
Both types of bone marrow are enriched with blood vessels and capillaries.2
Bone marrow makes more than 200 billion new blood cells every day.8 Most blood cells in the body develop from cells in the bone marrow.5
Bone marrow stem cells
The bone marrow contains two types of stem cells, mesenchymal and hematopoietic.
Red bone marrow consists of a delicate, highly vascular fibrous tissue containing hematopoietic stem cells. These are blood-forming stem cells.
Yellow bone marrow contains mesenchymal stem cells, also known as marrow stromal cells. These produce fat, cartilage, and bone.4
Stem cells are immature cells that can turn into a number of different types of cell.
Hematopoietic stem cells in the bone marrow give rise to two main types of cells: myeloid and lymphoid lineages. These include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes or platelets, as well as T cells, B cells, and natural killer cells.
The different types of hematopoietic stem cells vary in their regenerative capacity and potency.
Some are multipotent, oligopotent or unipotent as determined by how many types of cell they can create.
Pluripotent hematopoietic stem cells have the following properties:
- Renewal: They can reproduce another cell identical to themselves.
- Differentiation: They can generate one or more subsets of more mature cells.
The process of development of different blood cells from these pluripotent stem cells is known as hematopoiesis.11
It is these stem cells that are needed in bone marrow transplant.
Stem cells constantly divide and produce new cells. Some new cells remain as stem cells and others go through a series of maturing stages, as precursor or blast cells, before becoming formed, or mature, blood cells. Stem cells rapidly multiply to make millions of blood cells each day.10
Blood cells have a limited life span. This is around 100-120 days for red blood cells. They are constantly being replaced. The production of healthy stem cells is vital.12
The blood vessels act as a barrier to prevent immature blood cells from leaving the bone marrow.
Only mature blood cells contain the membrane proteins required to attach to and pass through the blood vessel endothelium. Hematopoietic stem cells can cross the bone marrow barrier, however. These may be harvested from peripheral, or circulating, blood.15
The blood-forming stem cells in red bone marrow can multiply and mature into three significant types of blood cells, each with their own job:
- Red blood cells (erythrocytes) transport oxygen around the body
- White blood cells (leukocytes) help fight infection and disease. White blood cells include lymphocytes - the cornerstone of the immune system - and myeloid cells which include granulocytes: neutrophils, monocytes, eosinophils, and basophils
- Platelets (thrombocytes) help with clotting after injury. Platelets are fragments of the cytoplasm of megakaryocytes, another bone marrow cell.
Once mature, these blood cells move from the marrow into the bloodstream, where they perform important functions required to keep the body alive and healthy.7
Mesenchymal stem cells are found in the bone marrow cavity. They differentiate into a number of stromal lineages, such as:
- chondrocytes (cartilage generation)
- osteoblasts (bone formation)
- adipocytes (adipose tissue)
- myocytes (muscle)
- endothelial cells
Red bone marrow
Red bone marrow produces all red blood cells and platelets in human adults and around 60 to 70 percent of lymphocytes. Other lymphocytes begin life in the red bone marrow and become fully formed in the lymphatic tissues, including the thymus, spleen, and lymph nodes.1
Together with the liver and spleen, red bone marrow also plays a role in getting rid of old red blood cells.
Yellow bone marrow
Yellow bone marrow mainly acts as a store for fats. It helps to provide sustenance and maintain the correct environment for the bone to function. However, under particular conditions, such as severe blood loss or fever, the yellow marrow may revert to red marrow.1
Yellow marrow tends to be located in the central cavities of long bones, and is generally surrounded by a layer of red marrow with long trabeculae (beam-like structures) within a sponge-like reticular framework.6
Bone marrow timeline
Before birth, bone marrow first develops in the clavicle toward the end of fetal development. It becomes active about 3 weeks later. Bone marrow takes over from the liver as the major hematopoietic organ at 32 to 36 weeks' gestation.
Bone marrow remains red until around the age of 7 years, as the need for new continuous blood formation is high. As the body ages, the red marrow is gradually replaced by yellow fat tissue. Adults have an average of about 2.6 kg (5.7 lbs) of bone marrow, about half of which is red.3
In adults, the highest concentration of red marrow is in the bones of the vertebrae, hips (ilium), breastbone (sternum), ribs, skull and at the metaphyseal and epiphyseal ends of the long bones of the arm (humerus) and leg (femur and tibia). All other cancellous, or spongy, bones and central cavities of the long bones are filled with yellow marrow.
Most red blood cells, platelets, and most of the white blood cells are formed in the red marrow. Yellow bone marrow produces fat, cartilage, and bone.
Blood cell formation from differentiation of hematopoietic stem cells in red bone marrow.
White blood cells survive from a few hours to a few days, platelets for about 10 days, and red blood cells for about 120 days. These cells must be constantly replaced by the bone marrow, as each blood cell has a set life expectancy.
Certain conditions may trigger additional production of blood cells. This may happen when the oxygen content of body tissues is low, if there is loss of blood or anemia, or if the number of red blood cells decreases. If these happen, the kidneys produce and release erythropoietin, a hormone that stimulates the bone marrow to produce more red blood cells.
The bone marrow also produces and releases more white blood cells in response to infections, and more platelets in response to bleeding. If a person experiences serious blood loss, yellow bone marrow can be activated and transformed into red bone marrow.
Healthy bone marrow is important for a range of systems and activities.
The circulatory system touches every organ and system in the body. It involves a number of different cells with a variety of functions. Red blood cells transport oxygen to cells and tissues, platelets are carried in the blood to help blood clot after injury, and white blood cells are transported to sites of infection or injury.
Hemoglobin is the protein in red blood cells that gives them their color. Hemoglobin collects oxygen in the lungs, transports it in the red blood cells, and releases oxygen to tissues such as the heart, muscles, and brain. Carbon dioxide (CO2), a waste product of respiration, is also removed by hemoglobin and sent back to the lungs to be exhaled.
Iron is an important nutrient for human physiology. It combines with protein to make the hemoglobin in red blood cells and is essential in the production of red blood cells (erythropoiesis). The body stores iron in the liver, spleen, and bone marrow. Most of the iron needed each day for making hemoglobin comes from the recycling of old red blood cells.
Red blood cells
The production of red blood cells is called erythropoiesis. It takes about 7 days for a committed stem cell to mature into a fully functional red blood cell. As red blood cells age, they become less active and more fragile.
Aging red cells are removed or eaten up by a type of white blood cell, or macrophage, in a process known as phagocytosis. The contents of these cells are released into the blood. The iron released in this process is carried to either the bone marrow for production of new red blood cells or to the liver or other tissues for storage.
Normally, around 1 percent of the body's total red blood cells are replaced every day. In a healthy person, around 200 billion red blood cells are produced each day.
White blood cells
The bone marrow produces many types of white blood cells. These are necessary for a healthy immune system. They prevent and fight infections.
The main types of white blood cell, or leukocyte, are:
Lymphocytes are produced in bone marrow. They make natural antibodies to fight infection caused by viruses that enter the body through the nose, mouth or other mucous membrane, or through cuts and grazes. Specific cells recognize the presence of foreign invaders (antigens) that enter the body and send a signal to other cells to attack the antigens.
The number of lymphocytes increases in response to these invasions. There are two major types of lymphocyte: B- and T-lymphocytes.
Monocytes are produced in the bone marrow. Mature monocytes have a life expectancy in the blood of only 3 to 8 hours, but when they move into the tissues, they mature into larger cells called macrophages. Macrophages can survive in the tissues for long periods of time where they engulf and destroy bacteria, some fungi, dead cells, and other material foreign to the body.
Granulocyte is the family or collective name given to three types of white blood cells: neutrophils, eosinophils and basophils. The development of a granulocyte may take two weeks, but this time is shortened when there is an increased threat, such as a bacterial infection.
Bone marrow stores a large reserve of mature granulocytes. For every granulocyte circulating within the blood, there may be 50 to 100 cells waiting in the marrow to be released into the blood stream. As a result, half the granulocytes in the blood stream can be available to actively fight an infection in the body within 7 hours of detecting an infection.
Once a granulocyte has left the blood, it does not normally return. A granulocyte may survive in the tissues for up to 4 to 5 days, depending on the conditions, but it only survives for a few hours in the circulation.
Neutrophils are the most common granulocyte. They can attack and destroy bacteria and viruses.
Eosinophils are involved in the fight against many types of parasitic infections and against the larvae of parasitic worms and other organisms. They are also involved in some allergic reactions.
Basophils are the least common of the white blood cells and respond to various allergens that cause the release of histamines, heparin, and other substances.
Heparin is an anticoagulant. It prevents blood from clotting. Histamines are vasodilators that cause irritation and inflammation. Releasing these substances makes a pathogen more permeable, and allows for white blood cells and proteins to enter tissues to engage the pathogen.
Bone marrow produces platelets in a process known as thrombopoiesis. Platelets are needed for blood to coagulate and for clots to form, to stop bleeding.
Sudden blood loss triggers platelet activity at the site of an injury or wound. Here, the platelets clump together and combine with other substances to form fibrin. Fibrin has a thread-like structure and forms an external scab or clot.
Platelet deficiency causes the body to bruise and bleed more easily. Blood may not clot well at an open wound, and there may be a greater risk for internal bleeding if the platelet count is very low.
The lymphatic system consists of lymphatic organs such as bone marrow, the tonsils, the thymus, the spleen and lymph nodes.
All lymphocytes develop in the bone marrow from immature cells called stem cells. Lymphocytes that mature in the thymus gland (behind the breastbone) are called T-cells. Those that mature in the bone marrow or lymphatic organs are called B-cells.14
The immune system protects the body from disease. It kills unwanted micro-organisms such as bacteria and viruses that may invade the body.
How does the immune system fight against infection?
Small glands called lymph nodes are scattered throughout the body. Once lymphocytes are made in the marrow, they travel to the lymph nodes. The lymphocytes can then travel between each node through lymphatic channels that meet at large drainage ducts that empty into a blood vessel. Lymphocytes enter the blood through these ducts.
Three major types of lymphocytes play an important part of the immune system:
These cells originate from hematopoietic stem cells in the bone marrow in mammals.
There are three types lymphocytes. T-lymphocytes, B-lymphocytes, and natural killer cells.
B-cells express B-cell receptors (BCRs) on the surface of the cells. These allow the cell to attach to an antigen on the surface of an invading microbe or other antigenic agent.
For this reason, B-cells are known as antigen-presenting cells as they alert other cells of the immune system to an invading microbe.
B-cells also secrete antibodies which attach to the surface of infection-causing microbes. These antibodies are Y-shaped, and each one is akin to a specialized "lock" into which a matching antigen "key" fits. As such, each Y-shaped antibody reacts to a different microbe, triggering a larger immune system response with the aim of fighting infection.
In some circumstances, B-cells erroneously identify the normal cells of the human body as being antigens that require an immune system response. This is the mechanism that lies behind the development of autoimmune diseases such as multiple sclerosis, scleroderma, and type 1 diabetes.
These cells are so-called because they mature in the thymus, a small organ in the upper chest, just behind the sternum (some T-cells mature in the tonsils). There are many different types of T-cells, and they perform a range of functions as part of adaptive cell-mediated immunity. T-cells help B-cells make antibodies against invading bacteria, viruses, or other microbes.
Unlike B-cells, some T-cells engulf and destroy pathogens directly, after binding to the antigen on the surface of the microbe.
Natural killer T-cells, not to be confused with natural killer cells of the innate immune system, bridge the adaptive and innate immune systems. NKT cells recognize antigens presented in a different way to many other antigens, and can perform the functions of T-helper cells and cytotoxic T-cells. They can also recognize and eliminate some tumor cells.
Natural killer (NK) cells
These are a type of lymphocyte that directly attacks cells which have been infected by a virus.
A bone marrow transplant can be used for various reasons.
- It can replace diseased, nonfunctioning bone marrow with healthy functioning bone marrow. This is used for conditions such as leukemia, aplastic anemia, and sickle cell anemia.
- It can regenerate a new immune system that will fight existing or residual leukemia or other cancers not killed by chemotherapy or radiation.
- It can replace bone marrow and restore its normal function after high doses of chemotherapy or radiation are given to treat a malignancy.
- It can replace bone marrow with genetically healthy, functioning bone marrow to prevent further damage from a genetic disease process, such as Hurler's syndrome and adrenoleukodystrophy.
Stem cells are primarily located in four places:
- an embryo
- bone marrow
- peripheral blood, found in blood vessels throughout the body
- cord blood, found in the umbilical cord and collected after birth9
Stem cells for transplantation are obtained from any of these except the fetus.
Stem cells can be obtained from bone marrow, peripheral blood, and cord blood.
Hematopoietic stem cell transplantation involves the intravenous infusion of stem cells collected from bone marrow, peripheral blood, or umbilical cord blood.
This is used to re-establish hematopoietic function in patients whose bone marrow or immune system is damaged or defective.17
More than 50,000 first hematopoietic stem cell transplantation procedures, 28,000 autologous transplantation procedures, and 21,000 allogeneic transplantation procedures are performed every year worldwide, according to the first report of the Worldwide Network for Blood and Marrow Transplantation.
This number continues to increase by 10 to 20 percent annually. Reductions in organ damage, infection, and severe, acute graft versus host disease (GVHD) seem to be contributing to improved outcomes.
In a study of 854 patients who had survived at least 2 years after autologous hematopoietic stem cell transplantation (HSCT) for hematologic malignancy, 68.8 percent were still alive 10 years after transplantation.17
Bone marrow transplant is the leading treatment for conditions that threaten bone marrow's ability to function, such as leukemia.
A transplant can help rebuild the body's capacity to produce blood cells and bring their numbers to normal levels. Illnesses that may be treated with a bone marrow transplant include both cancerous and noncancerous diseases.
Cancerous diseases may or may not specifically involve blood cells, but cancer treatment can destroy the body's ability to manufacture new blood cells.
A person with cancer will normally undergo chemotherapy before transplantation. This will eliminate the compromised marrow.
A matching donor, in most cases a close family member, then has their bone marrow harvested and readied for transplant
Types of bone marrow transplant
Types of bone marrow transplant include:
- Autologous transplant: patients receive their own stem cells taken from their peripheral or cord blood to replenish bone marrow
- Syngeneic transplant: patients receive stem cells from their identical twin
- Allogeneic transplant: patients receive matching stem cells from their sibling, parent or an unrelated donor
- Haploidentical transplantation: a treatment option for the approximately 70% of patients who do not have an HLA-identical matching donor
- Umbilical cord blood: a type of allogeneic transplant. Stem cells are removed from a newborn baby's umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. Umbilical cord blood cells are very immature so there is less of a need for matching, but blood counts take much longer to recover.
A person's tissue type is defined as the type of human leukocyte antigen (HLA) on the surface of most of the cells of their body. HLA is a protein or marker that the body uses to help it determine if the cell belongs to the body or not.
To check if the tissue type is compatible, doctors assess how many proteins match on the surface of the donor's and recipient's blood cells. There are millions of different tissue types but some are more common than others.
Tissue type is inherited, and types are passed on from each parent. This means a relative will be more likely to have a matching tissue type.
However, if a suitable bone marrow donor cannot be found from family members, doctors will try to find someone with a compatible tissue type on the bone marrow donor register.
Several tests are performed before the bone marrow transplant, to identify any potential problems.
- tissue typing and a variety of blood tests
- chest X-ray
- pulmonary function tests
- CT or CAT scans
- heart function tests including an electrocardiogram and echocardiogram (ECG)
- bone marrow biopsy
- skeletal survey
In addition, a complete dental exam is needed before a bone marrow transplant, to reduce the risk of infection. Other precautions will also be taken before the transplant to reduce the patient's risk of infection.
Harvesting bone marrow
Bone marrow can be obtained for examination by bone marrow biopsy and bone marrow aspiration.
The concentration of red marrow is highest in the bones of the hips (ilium). The doctor will insert a needle into the bone and withdraw some of the bone marrow, which is then stored and frozen.
Bone marrow harvesting has become a relatively routine procedure. It is generally aspirated from the posterior iliac crests while the donor is under either regional or general anesthesia.17
It can also be taken from the sternum, and from the upper tibia in children, because it still contains a substantial amount of red bone marrow.
The doctor will insert a needle into the bone, usually in the hip, and withdraw some of the bone marrow. It is then stored and frozen.
Guidelines established by the National Marrow Donor Program (NMDP) limit the volume of bone marrow removed to 15 mL/kg of donor weight. A dose of 1 X 103 and 2 X 108 marrow mononuclear cells per kilogram are required to establish engraftment in autologous and allogeneic marrow transplants, respectively.
Complications related to bone marrow harvesting are rare. They involve problems related to anesthesia, infection and bleeding.
Another way to evaluate bone marrow function is to give certain drugs that stimulate the release of stem cells from the bone marrow into circulating blood. The blood sample is then obtained, and stem cells are isolated for microscopic examination. In newborns, stem cells may be retrieved from the umbilical cord.
How is bone marrow transplanted?
Before the transplant, chemotherapy, radiation, or both may be given. This may be done in two ways:
Bone marrow product is infused through a central vein through an IV tube over a period of several hours.
- Ablative (myeloablative) treatment: High-dose chemotherapy, radiation, or both are given to kill any cancer cells. This also kills all healthy bone marrow that remains, and allows new stem cells to grow in the bone marrow
- Reduced intensity treatment, or a mini transplant: Patients receive lower doses of chemotherapy and radiation before a transplant. This allows older patients and those with other health problems to have a transplant.
A stem cell transplant is usually done after chemotherapy and radiation are complete.
The infusion of either bone marrow or peripheral blood is a relatively simple process that is performed at the bedside. The bone marrow product is infused through a central vein through an IV tube over a period of several hours. Autologous products are almost always cryopreserved; they are thawed at the bedside and infused rapidly over a period of several minutes.17
After entering the bloodstream, the hematopoietic stem cells travel to the bone marrow. There, they begin to produce new white blood cells, red blood cells, and platelets in a process known as engraftment. Engraftment usually occurs 2 to 4 weeks after transplantation.4
Minimal toxicity has been observed in most cases. ABO-mismatched bone marrow infusions can sometimes lead to hemolytic reactions. Dimethyl sulfoxide (DMSO), which is used for the cryopreservation of stem cells, may give rise to facial flushing, a tickling sensation in the throat, and a strong taste in the mouth (the taste of garlic). Rarely, DMSO can cause bradycardia, abdominal pain, encephalopathy or seizures, and renal failure.
To avoid the risk of encephalopathy, which occurs with doses above 2 g/kg/day of DMSO, stem cell infusions exceeding 500 mL are infused over 2 days, and the rate of infusion is limited to 20 mL/min.
Doctors regularly check blood counts. Complete recovery of immune function can take several months for autologous transplant recipients and 1 to 2 years for patients receiving allogeneic or syngeneic transplants.
Blood tests will confirm that new blood cells are being produced and that any cancer has not returned. Bone marrow aspiration can also help doctors determine how well the new marrow is working.4
Complications associated with HSCT include both early and late effects.17
Early-onset problems include:
- hemorrhagic cystitis
- prolonged, severe pancytopenia
- GVHD (Graft versus host disease)
- graft failure
- pulmonary complications
- hepatic veno-occlusive disease
- thrombotic microangiopathy
Late-onset problems include:
- chronic GVHD
- ocular effects
- endocrine effects
- pulmonary effects
- musculoskeletal effects
- neurologic effects
- immune effects
- congestive heart failure
- subsequent malignancy
Major risks include increased susceptibility to infection, anemia, graft failure, respiratory distress, and excess fluid, which can lead to pneumonia and liver dysfunction.
A mismatch between donor and recipient tissues can lead to an immune reaction between cells of the host and cells of the graft.
When graft cells attack host cells, the result is a dangerous condition called graft-versus-host disease (GVHD), which may be acute or chronic and may manifest as a skin rash, gastrointestinal illness, or liver disease. The risk of GVHD can be minimized through careful tissue matching.
Even when a donor antigen match is identical, roughly 40 percent of recipients still develop GVHD, rising to 60 to 80 percent when only a single antigen is mismatched. Because of the danger of this complication, autologous transplants are more commonly performed.
Bone marrow transplantation was not previously recommended for patients aged over 50 years, due to a higher mortality and morbidity rate and an increased incidence of GVHD in those over the age of 30 years. However, many transplant centers have performed successful bone marrow transplantations in patients well beyond the age of 50 years.
There is little risk to those who donate, because they generate new marrow to replace that which has been removed. There is, however, a slight risk of infection and a reaction to anesthesia can occur with any surgical procedure.
As bone marrow affects many body systems, a problem can result in a wide range of diseases, including cancers that affect the blood.
A number of diseases pose a threat to bone marrow because they prevent bone marrow from turning stem cells into essential cells.
Leukemia, Hodgkin's disease, and other lymphoma cancers are known to damage the marrow's productive ability and destroy stem cells.
A bone marrow examination can help diagnose:1
Blood smear showing neutrophil, white blood cell and leukemia.
- multiple myeloma
- Gaucher disease
- unusual cases of anemia
- other hematological diseases.
A growing number of diseases can be treated with hematopoietic stem cell transfer (HSCT).
More than half of autologous transplantations are done to treat multiple myeloma and non-Hodgkin lymphoma. Most allogeneic transplants are performed for hematologic and lymphoid cancers.
Every 4 minutes in the United States, someone receives a diagnosis of blood cancer. A bone marrow transplant is often the best chance for survival.
Around 30 percent of patients can find a matching donor in their families, but 70 percent, or around 14,000 each year, rely on marrow donated by someone unrelated.
Autologous HSCT is currently used to treat:
- multiple myeloma
- non-Hodgkin lymphoma
- Hodgkin lymphoma
- acute myeloid leukemia
- germ-cell tumors
- autoimmune disorders, such as systemic lupus erythematosus and systemic sclerosis
Allogeneic HSCT is used to treat:
- acute myeloid leukemia
- acute lymphoblastic leukemia
- chronic myeloid leukemia
- chronic lymphocytic leukemia
- myeloproliferative disorders
- myelodysplastic syndromes
- multiple myeloma
- non-Hodgkin lymphoma
- Hodgkin lymphoma
- aplastic anemia
- pure red cell aplasia
- paroxysmal nocturnal hemoglobinuria
- fanconi anemia
- thalassemia major
- sickle cell anemia
- severe combined immunodeficiency (SCID)
- Wiskott-Aldrich syndrome
- hemophagocytic lymphohistiocytosis
- genetic disorders relating to metabolism, such as mucopolysaccharidosis
- Gaucher disease, metachromatic leukodystrophies, and adrenoleukodystrophies
- epidermolysis bullosa
- severe congenital neutropenia
- Shwachman-Diamond syndrome
- Diamond-Blackfan anemia
- leukocyte adhesion deficiency
HSCT may also help treat:17
- breast cancer, although this is not confirmed
- testicular cancer, in some patients at the early stage
- some genetic immunologic or hematopoietic disorders
Bone marrow transplants are sometimes needed after certain treatments, such as high-dose chemotherapy and radiation therapy, used to treat cancer. These treatments tend to damage healthy stem cells as well as destroying cancer cells.
Bone marrow tests
Bone marrow tests can help diagnose certain diseases, especially those related to blood and blood-forming organs. Testing provides information on iron stores and blood production.1
Bone marrow aspiration uses a hollow needle to remove a small sample (about 1 ml) of bone marrow for examination under a microscope.
The needle is usually inserted into the hip or sternum in adults and into the upper part of the tibia (the larger bone of the lower leg) in children and suction is used to extract the sample.
Bone marrow aspiration is typically performed when indicated by previous blood tests and is particularly useful in providing information on various stages of immature blood cells.
There are two main types of bone marrow donation.
It is blood stem cells, rather than the bone marrow itself, which are necessary for the treatment of blood cancers and other diseases.
The first involves the removal of bone marrow from the back of the pelvic bone.
The second, more common method, is called peripheral blood stem cell (PBSC) donation. This involves filtering stem cells directly from the blood. It is these blood stem cells, rather than the bone marrow itself, which are necessary for the treatment of blood cancers and other diseases.
When an individual joins a bone marrow donation registry, they are agreeing to donate using whichever method the patient's doctor deems appropriate.
In terms of costs, the expense of making a blood marrow donation is usually covered by either the NMDP or the patient's medical insurance. Donors never pay for donating, and they are never paid to donate.
The risk to a donor is minimal. Over 99 percent of donors make a full recovery after the procedure. With blood marrow donation, the major risk involves the use of anesthesia during the procedure itself.
With PBSC donation, the procedure itself, which involves filtering blood through a machine, is not considered dangerous.
The chance of finding a suitable bone marrow donor ranges from 66 to 93 percent, depending on ethnicity.
Who can donate bone marrow8
The following are some general guidelines for bone marrow donation as recommended by the National Marrow Donor Program (NMDP).
The guidelines aim to protect the health and safety of the donor and the recipient. Donors are encouraged to contact their local NMDP center for specific details and to discuss donations with their health care team.
- To be listed in the registry, potential donors must be healthy and between the ages of 18 and 60 years.
- If matched with a person needing a transplant, each donor must pass a medical examination and be infection-free before donating.
- People who used medications can normally donate bone marrow, as long as they are healthy and any medical conditions they have are under control at the time of donation.
Acceptable medications include birth control pills, thyroid medication. antihistamines, antibiotics, prescription eye drops, and topical medications, such as skin creams. Antianxiety and antidepressant drugs are allowed as long as the condition is under control.
Donate is not possible:
- during pregnancy
- by anyone using intravenous drugs that are not prescribed by a doctor
- if the person has had a positive blood test for hepatitis B or hepatitis C
- by those with specific medical conditions, such as most types of cancer or certain heart conditions
How is a bone marrow match determined?
After registering to donate, the person will undertake an HLA-typing test, which is used to match up patients with potential donors.
Their HLA type will then be added to a database of potential donors, and a doctor will search the registry to try to find a match for their patient.
The proteins in the blood cells will be compared to see if they are similar to those of the recipient. The potential donor will be contacted if there is a match.
The more similar the donor's tissue type is to the patient's, the better the chance of the patient's body accepting the transplant.
Bone Marrow Donors Worldwide (BMDW) is a collective database of 59 registries in 43 countries, and 37 cord blood registries from 21 countries; 26.35 million potential stem cell donors and 687 thousand cord blood units were available as of September 2015.19,20 Preliminary searches through the NMDP routinely also explore the BMDW.
What happens when donating bone marrow?
The following studies are routinely performed on hematopoietic stem cell donors:
Donating peripheral blood stem cells involves taking the blood using a catheter inserted in one arm, and passing the blood through a machine which filters out the stem cells.
- history and physical examination
- serum creatinine, electrolyte, and liver function studies
- serologic studies for cytomegalovirus (CMV), herpes viruses, HIV RNA, anti-HIV antibodies, hepatitis B and C viruses, human T-cell lymphotropic virus-1/2 (HTLV-I/II), and syphilis (VDRL); in autologous donations, CMV and VDRL testing are not required
- ABO blood typing
- HLA typing
- chest radiography
- Electrocardiography (ECG)
Donating peripheral blood stem cells (PBSC)
Before a person can donate PBSC, they will need to undergo daily injections of a medication called filgrastim in the five days running up to the procedure. This medication draws stem cells from the bone marrow, so the donor will have more of them circulating in their blood.
Donating PBSC involves a procedure known as apheresis. This is when blood is taken from the body using a catheter inserted in one arm and passed through a machine, filtering out the stem cells, along with platelets and white blood cells. The remaining blood (consisting mainly of plasma and red blood cells) then flows back into the body through a vein in the other arm.
The procedure is completely painless and is similar to donating plasma. PBSC donation will usually require between two and four sessions, each lasting 2 to 6 hours.
PBSC donation does not require anesthesia. The medication that is given to stimulate the mobilization (release) of stem cells from the marrow into the bloodstream may cause bone and muscle aches, headaches, fatigue, nausea, vomiting, or difficulty sleeping. These side effects usually stop within 2 to 3 days of the last dose of the medication.
Donating bone marrow
If a person is donating actual bone marrow instead of PBSC, there is no need for the filgrastim injections. Bone marrow donation is a surgical procedure, carried out in the operating room, which requires anesthesia and is, therefore, completely painless. The entire procedure takes between 1 and 2 hours.
In 96 percent of cases, a general anesthetic is used, which means the donor will be unconscious for the entire procedure. In a small number of cases a local anesthetic will be used, which simply numbs the area the bone marrow is taken from. In this situation, the person will be awake throughout the procedure.
The person lies on their stomach. The doctors will make an incision about a quarter of an inch in length on both sides of the pelvic bone. They then insert special, hollow needles into the bone, through which they draw the liquid marrow. The incisions do not normally require stitches.
After the procedure, the donor will stay in a recovery room until they regain consciousness. Once they can eat, drink and walk, they will be able to leave.
After donation, complete recovery may take a couple of days, especially if surgery was involved.
People who donate bone marrow often experience headaches, fatigue, muscle pain, back or hip pain, bruising around the incision site, and difficulty walking. This may persist for up to 2 days, or as long as several weeks.
A person who donates PBSC is unlikely to experience any side effects following the donation, other than bruising at the needle site. Recovery time is almost immediate.
After donation, bone marrow replaces itself within 4 to 6 weeks.
The outcome of bone marrow transplant depends on:
- the type of transplant
- how closely the cells match
- what type of condition the patient has
- the patient's age and overall health
- the type and dosage of chemotherapy or radiation therapy used before transplant
- any complications
A patient whose condition is stable or in remission has a better chance of a good outcome compared with someone who has a transplant in a later stage or with relapsed disease. Young age at time of transplant also improves the chances.
Transplants for nonmalignant diseases tend to have more favorable outcomes, with survival rate of 70 to 90 percent if the donor is a matched sibling, and 36 to 65 percent if the donor is unrelated.
Transplants for acute leukemia in remission at the time of transplant have survival rates of 55 to 68 percent if the donor is related, and 26 to 50 percent if the donor is unrelated.
A bone marrow transplant may completely or partially cure illness. If the transplant is successful, individuals can go back to most normal activities as soon as they feel well enough. Full recovery normally takes up to a year.