Bone Marrow Transplant

Institue of Bone Marrow Transplant

Bone Marrow Transplant explorehealth

Explore Institute of Bone Marrow Transplant & Research is working with various Cancer Research Group with China, India, Canada, USA and Australia. We have participated more than 12 international Health Research Programs.

What is Bone Marrow?
Bone marrow is soft, gelatinous tissue that fills the medullary cavities - the centers of bones. There are two types of bone marrow: red bone marrow (also known as myeloid tissue) and yellow bone marrow (fatty tissue). Both types of bone marrow are highly vascular and enriched with numerous blood vessels and capillaries. The bone marrow makes more than 200 billion new blood cells every day. Most blood cells in the body develop from cells in the bone marrow.

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What Does Bone Marrow Do?
Bone marrow is the spongy tissue inside some of the bones in the body, including the hip and thigh bones. Bone marrow contains immature cells, called stem cells. Numerous people with blood cancers such as leukemia and lymphoma, sickle cell anemia and other life-threatening diseases, rely on bone marrow or cord blood transplants to survive.

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.

What is a bone marrow transplant?
A bone marrow transplant can be used to: - Replace diseased, nonfunctioning bone marrow with healthy functioning bone marrow (for conditions such as leukemia, aplastic anemia, and sickle cell anemia).
- Regenerate a new immune system that will fight existing or residual leukemia or other cancers not killed by chemotherapy or radiation.
- Replace bone marrow and restore its normal function after high doses of chemotherapy or radiation are given to treat a malignancy.
- 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) and cord blood (found in the umbilical cord and collected after the baby's birth). Stem cells for transplantation are obtained from any of the latter three sources.

Hematopoietic stem cell transplantation involves the intravenous infusion of stem cells collected from bone marrow, peripheral blood, or umbilical cord blood to re-establish hematopoietic function in patients whose bone marrow or immune system is damaged or defective.

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, per the first report of the Worldwide Network for Blood and Marrow Transplantation.

This number continues to increase by 10-20% annually, and 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% were still alive 10 years after transplantation.

A number of diseases, many of which are incurable, pose a threat to bone marrow. 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.

The leading treatment for conditions that threaten bone marrow's ability to function is a bone marrow transplant. A bone marrow transplant is used to 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. This procedure typically begins with chemotherapy to 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:
- 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.

Tissue type
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 check how many proteins on the surface of the blood cells match. There are millions of different tissue types but some are more common than others. Tissue type is inherited, with these types being 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.

Reasons for bone marrow transplants
The list of diseases for which hematopoietic stem cell transfer (HSCT) is being used is increasing rapidly. More than half of autologous transplantations are performed for multiple myeloma and non-Hodgkin lymphoma, and the vast majority of allogeneic transplants are performed for hematologic and lymphoid cancers. Every 4 minutes in the US, someone is diagnosed with a blood cancer. For many patients, a bone marrow transplant is the best chance for survival. While 30% of patients can find a matching donor in their families, 70% - approximately 14,000 each year - must rely on marrow donated by someone unrelated.

Autologous HSCT is currently used to treat the following conditions:
- Multiple myeloma
- Non-Hodgkin lymphoma
- Hodgkin lymphoma
- Acute myeloid leukemia
- Neuroblastoma
- Germ cell tumors
- Autoimmune disorders (systemic lupus erythematosus, systemic sclerosis)
- Amyloidosis

Allogeneic HSCT is used to treat the following disorders:
- 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
- Inborn errors of metabolism - E.g., mucopolysaccharidosis
- Gaucher disease, metachromatic leukodystrophies and adrenoleukodystrophies
- Epidermolysis bullosa
- Severe congenital neutropenia
- Shwachman-Diamond syndrome
- Diamond-Blackfan anemia
- Leukocyte adhesion deficiency

HSCT may also be effective in the treatment of the following conditions:
- Breast cancer : HSCT in breast cancer patients is debatable
- Testicular cancer : The achievement of disease-free survival in a minority of patients with severe disease suggests much better results if performed earlier
- Thalassemia : An 80% disease-free survival rate is achieved after allogeneic HSCT
- Sickle cell anemia : Sickle cell anemia is potentially curable with allogeneic HSCT
- Genetic disorders : Many genetic immunologic or hematopoietic disorders are potentially curable with allogeneic HSCT. Bone marrow transplants are also sometimes necessary following certain treatments, such as high-dose chemotherapy and radiation therapy, which are often used to treat cancer. These treatments tend to damage healthy stem cells as well as destroying cancer cells.

Diagnosis and preparation:
Several tests are performed before the bone marrow transplant, to identify any potential problems. Tests include:

- Tissue typing and a variety of blood tests

- Chest X-ray
- Pulmonary function tests
- Computed tomography scan (CT or CAT scan)
- Heart function tests including an electrocardiogram and echocardiogram
- Bone marrow biopsy
- Skeletal survey.

In addition, a complete dental exam is needed, before 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.

How is bone marrow harvested?
Bone marrow can be obtained for examination by bone marrow biopsy and bone marrow aspiration. Bone marrow harvesting has become a relatively routine procedure and is generally aspirated from the posterior iliac crests while the donor is under either regional or general anesthesia. The sternum can also be used as an aspiration site, as can 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, which 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 and involve problems related to anesthesia, infection and bleeding. Another option for evaluating bone marrow function is to administer 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 does a bone marrow transplant occur?
Before the transplant, chemotherapy, radiation, or both may be given. This may be done in two ways:
- 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, also called a mini transplant: patients receive lower doses of chemotherapy and radiation before a transplant, which 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. After entering the bloodstream, the hematopoietic stem cells travel to the bone marrow, where 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. Minimal toxicity has been observed in most cases. ABO-mismatched bone marrow infusions can occasionally 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/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 check blood counts on a frequent basis. Complete recovery of immune function takes up to several months for autologous transplant recipients and 1 to 2 years for patients receiving allogeneic or syngeneic transplants. Doctors evaluate the results of various blood tests to confirm that new blood cells are being produced and that the cancer has not returned. Bone marrow aspiration can also help doctors determine how well the new marrow is working.

What are the risks of bone marrow transplants?
Complications associated with HSCT include both early and late effects.17 Early-onset problems include the following:
- Mucositis
- Hemorrhagic cystitis
- Prolonged, severe pancytopenia
- Infection
- GVHD (Graft versus host disease)
- Graft failure
- Pulmonary complications
- Hepatic veno-occlusive disease
- Thrombotic microangiopathy.

Late-onset problems include the following:
- Chronic GVHD
- Ocular effects
- Endocrine effects
- Pulmonary effects
- Musculoskeletal effects
- Neurologic effects
- Immune effects
- Infection
- Congestive heart failure
- Subsequent malignancy.

Major risks associated with bone marrow transplant include increased susceptibility to infection, anemia, graft failure, respiratory distress, and excess fluid, which can lead to pneumonia and liver dysfunction. In addition, 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. However, even when a donor antigen match is identical, roughly 40% of recipients still develop GVHD. This figure increases to between 60-80% 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 recommended initially for patients over the age of 50 due to a higher mortality and morbidity rate and an increased incidence of GVHD in those over the age of 30. However, many transplant centers have performed successful bone marrow transplantations in patients well beyond the age of 50. People who donate bone marrow incur little risk because they generate new marrow to replace that which has been removed. There is, however, a slight risk of infection and reaction to anesthesia with any surgical procedure.

FACTS ON BONE MARROW:

Here are some key points about bone marrow:
- A bone marrow transplant can save the lives of people battling leukemia, lymphoma and other blood cancers.
- At birth, all bone marrow is red. As humans age, red marrow increasingly begins to convert to yellow marrow.
- In adults, around half of the bone marrow is red and half is yellow. - 200 billion new red blood cells are made by the bone marrow every day, along with white blood cells and platelets.
- Around 1% of the body's red blood cells are regenerated every day.
- Healthy bone marrow manufactures between 150,000 and 450,000 platelets per microliter of blood, the amount of blood that fits on the head of a pin.
- 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.
- 7 out of 10 people who require a bone marrow transplant do not have a matching donor in their family, and rely on the registry of bone marrow donors to find a match.
- The process for matching a patient with a donor involves comparing human leukocyte antigen (HLA) types in order to find a match.
- Several diseases, many of which are incurable, pose a threat to bone marrow and prevent bone marrow from turning stem cells into essential cells.

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