A Bone Marrow Transplant is the most effective and in some case the only curative treatment for many blood disorders such as Aplastic Anemia, Sickle Cell Disorder, Leukemia and Thalasemmia and multiple sclerosis.

 

What is Bone Marrow:

Bone Marrow is something you must have heard a lot in recent years. Let us try to understand what it is in layman terms.

The soft blood-forming tissue that fills the cavities of bones and contains fat and immature and mature blood cells, including white blood cells, red blood cells, and platelets. Bone marrow may be found within the spongy or cancellous portions of bones. Diseases or drugs that affect the bone marrow can affect the total counts of these cells. 

There are two types of bone marrow: 

  • RED BONE MARROW, known as myeloid tissue. It is mainly responsible for the production of blood cells.
  • YELLOW BONE MARROW, which is basically the fatty tissue.

Both types of bone marrow are enriched with blood vessels and capillaries.  Most blood cells in the body develop from cells in the bone marrow.

Anatomy of the bone: The bone is made up of compact bone, spongy bone, and bone marrow. Compact bone makes up the outer layer of the bone. Spongy bone is found mostly at the ends of bones and contains red marrow. Bone marrow is found in the centre of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow marrow is made mostly of fat.

In human beings, bone marrow is the primary site of new blood cell production or haematopoiesis. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. On average, bone marrow constitutes 4% of the total body mass of humans.

Human marrow produces approximately 500 billion blood cells per day, which join the circulation. All types of blood forming cells, including both myeloid and lymphoid lineages, are created in bone marrow. The lymphoid cells must then migrate to other lymphoid organs (e.g. thymus) in order to complete maturation.

 

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.

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 haematopoiesis.

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 a precursor or blast cells, before becoming formed, or mature, blood cells. Stem cells rapidly multiply to make millions of blood cells each day.

Blood cells have a limited lifespan. This is around 100-120 days for red blood cells. They are constantly being replaced. The production of healthy stem cells is vital.

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.

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.

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)
  • Osteoclasts
  • Adipocytes (adipose tissue)
  • Myocytes (muscle)
  • Macrophages
  • Endothelial cells
  • Fibroblasts.

 

What is Bone Marrow Transplant?

Now that we know what actually bone marrow is, we can now focus on the main topic of the article. A bone marrow transplant can be used for various reasons.

  • It can replace diseased, non-functioning bone marrow with healthy functioning bone marrow. This is used for conditions such as leukaemia, aplastic anaemia, and sickle cell anaemia.
  • It can regenerate a new immune system that will fight existing or residual leukaemia 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 birth

Stem cells for transplantation are obtained from any of these except the foetus.

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.

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.

Bone marrow transplant is the leading treatment for conditions that threaten bone marrow's ability to function, such as leukaemia.

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. Autologous transplant requires the extraction (apheresis) of haematopoietic stem cells from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population. The patient's own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the patient's normal blood cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment since the recovery of immune function is rapid. Also, the incidence of patients experiencing rejection (and graft-versus-host disease is impossible) is very rare due to the donor and recipient being the same individual. These advantages have established autologous transplant as one of the standard second-line treatments for such diseases as lymphoma.
  • Syngeneic transplant: Patients receive stem cells from their identical twin. A monozygotic or 'identical' twin of the patient, having the same DNA, turn out to be a perfect match in most of the cases.
  • Allogeneic transplant: Patients receive matching stem cells from their sibling, parent or an unrelated donor. Allogeneic Transplant involves two people: the (healthy) donor and the (patient) recipient. Allogeneic Transplant donors must have a tissue type that matches the recipient. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA matched sibling), syngeneic or unrelated (a donor who is not related and found to have a very close degree of HLA matching).
  • 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 new-born 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 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.

 

Pre-transplant Tests:

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
  • 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 anaesthesia.

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 anaesthesia, 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 new-born, stem cells may be retrieved from the umbilical cord.

 

Diseases in which BMT is Indicated:

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.

Leukaemia, 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 leukaemia.

  • leukaemia
  • multiple myeloma
  • Gaucher disease
  • unusual cases of anaemia
  • other haematological diseases.

2.) A growing number of diseases can be treated with hematopoietic stem cell transfer.

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.

3.) Autologous HSCT is currently used to treat:

  • multiple myeloma
  • non-Hodgkin lymphoma
  • Hodgkin lymphoma
  • acute myeloid leukaemia
  • autoimmune disorders, such as systemic lupus erythematosus and systemic sclerosis
  • amyloidosis
  • Allogeneic HSCT is used to treat:
  • acute myeloid leukaemia
  • acute lymphoblastic leukaemia
  • chronic myeloid leukaemia
  • chronic lymphocytic leukaemia
  • myeloproliferative disorders
  • myelodysplastic syndromes
  • multiple myeloma
  • non-Hodgkin lymphoma
  • Hodgkin lymphoma
  • aplastic anaemia
  • pure red cell aplasia
  • paroxysmal nocturnal haemoglobinuria
  • fanconi anaemia
  • thalassemia major
  • sickle cell anaemia
  • genetic disorders relating to metabolism, such as mucopolysaccharidosis
  • severe congenital neutropenia

HSCT may also help treat:

  • 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.

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.

 

Risk Involved:

Stem cell or bone marrow transplants are complex treatments that carry a significant risk of serious complications. Generally, younger people who don't have any other serious conditions or those who receive transplants from a closely matched sibling are less likely to experience serious problems. People receiving transplants of their own stem cells (autologous transplants) are also less likely to experience serious side effects. The main risks of a blood and marrow stem cell transplant are infections, graft-versus-host disease (GVHD), and graft failure.

 

Graft-Versus-Host Disease (GVHD):

In some cases, the transplanted cells recognize the recipient's cells as "foreign" and attack them. This is known as graft versus host disease (GVHD). At times these cells can recognize their own tissues as being foreign and attack them. This can be an advantage as they may also attack any cancer cells that are left after the treatment.  It can occur within a few months of the transplant or develop several months or occasionally a year or two later. The condition is usually mild but can sometimes be life-threatening.

 

Symptoms of GVHD Includes:
  • an itchy rash
  • diarrhoea
  • feeling and being sick
  • a sensitive and dry mouth 
  • dry eyes
  • dry, flaky skin
  • shortness of breath
  • Joint pain
  • yellowing of the skin and whites of the eyes.

If a patient develops GVHD after the transplant, doctor will prescribe drugs to damp down the immune reaction. These drugs are called immunosuppressive.
 

Infections:

Patients can easily catch infections after the transplant because of the weak immune system. The risk of infections decreases as the immune system recovers.

Following steps can be taken to prevent infections:

  • Room must be thoroughly cleaned on daily basis.
  • Bathing or showering daily
  • Carefully cleaning the teeth and gums
  • Cleaning the area where the central line enters the body
  • Avoiding foods that may have harmful bacteria, such as raw fruits and vegetables
  • Avoid having lightly cooked or raw eggs.

Transplant recipients sometimes are given vaccines to prevent viruses and infections, such as the flu and pneumonia. If a patient develops an infection, the treating doctor will prescribe medicines to treat.

Graft failure occurs if the immune system rejects the new stem cells. It also can occur if

  • Not enough stem cells are used,
  • The new stem cells are damaged during storage,
  • Bone marrow is damaged after the transplant.
  • People who get stem cells from poorly matched donors also are more likely to have graft failure.
  • It is also more likely to occur in people who receive less preparation for their transplants.

Prognosis: After you get the transplantation, the future of transplantation depends on:

  • The type of bone marrow transplant done
  • How well the donor's cells match the patients cell
  • What type of cancer or illness the patient is suffering
  • Patients age and overall health
  • The type and dosage of chemotherapy or radiation therapy the patient had undergone before the transplant.
  • Any complications the patient may have

A bone marrow transplant may completely or partially cure the illness. If the transplant is a success, the patient can go back to most of the normal activities as soon as the patient feel well enough. Usually it takes up to 1 year to recover fully, depending on what complications occur. Complications or failure of the bone marrow transplant can lead to death.

If you are being advised a bone marrow transplant for any condition, contact us for details and our team will assist you with in-depth information on cost , survival chances, success rate and eligibility to get a bone marrow transplant. Our empanelled doctors have a combined 400+ successful bone marrow transplant surgery experience. 

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