WHO MIGHT NEED A BONE MARROW TRANSPLANT?

Bone marrow transplants are considered as treatment for a variety of diseases, including leukaemias, haematological malignancies, congenital metabolic disorders and immune-deficiency illnesses.

Leukaemia

The majority of patients brought to the attention ofThe Anthony Nolan Bone Marrow Trust are suffering from leukaemia. This disease, often defined in lay terms as ‘cancer of the blood’, results from the excessive growth of particular cells present in normal bone marrow.

Approximately 4,000 new cases of leukaemia are diagnosed in the UK each year.

As the incidence of leukaemia increases with age but bone marrow transplants are usually only performed on people under 50, not all patients will be considered suitable for this treatment.

However, as different types of leukaemia have different age distributions, patients recommended for transplant will typically be suffering from one of the following three diseases:

Acute myeloid leukaemia

There are around 2,000 new cases of acute myeloid leukaemia diagnosed in the UK each year. It is treated with combinations of chemotherapy and a patient’s blood and marrow can frequently be restored to normal, enabling them to secure a complete remission (the absence of leukaemic cells) for many years. Achieving a total cure for certain subtypes of AML by drug treatment alone is unlikely and patients in remission can relapse. In this sub-group, if a compatible donor is found, bone marrow transplantation can cure AML.

Acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia accounts for 85% of the leukaemias in children and about 650 new cases are diagnosed annually in Britain. Without treatment the disease may cause death within a few weeks or months, however over 90% of patients respond to chemotherapy. Up to 70% of children and between 30 - 50% of young adults can look forward to being cured by the continuation of this treatment and remain in remission. However, for patients considered to have a high risk of relapse (usually if they are older or have a high leukaemic cell count when they are diagnosed), or for those who do actually relapse, the doctor may recommend a bone marrow transplant if a suitable donor can be found.

Chronic myeloid leukaemia

Chronic myeloid leukaemia is the rarest of all leukaemias. It is more common in the older population. Typically chemotherapy treatment aims to control it. The only known long term cure is a bone marrow transplant, for those diagnosed at a younger age who have a suitable donor.

Myelodyplastic and myeloproliferative syndromes

Myelodyplastic syndromes are a group of malignant disorders characterised by "dysplastic" (ineffective) blood cell production progressing onto bone marrow failure. There is a quantitative and qualitative abnormality of all white blood cells, red blood cells and platelets. A significant proportion transform to acute myeloid leukaemia. The majority of cases are diagnosed in the elderly with less than 10% presenting under the age of 50. As a result, the number of patients recommended for a bone marrow transplant is small.

Included in the category of myeloproliferative disorders is myelofibrosis. This is where there is an increase in bone marrow fibroblasts (cells which produce collagen fibres). Therefore the bone marrow cavity becomes obliterated by fibrous tissue resulting in bone marrow failure and an increase in the size of the spleen as it tries to take over the blood cell production). This condition is again rare at a young age and therefore treatment by bone marrow transplant is not common.

Multiple myeloma

This is a malignant proliferation of plasma cells which are responsible for manufacturing immunoglobins as part of the function of the immune system. It is scarce in people under the age of 50 and only in rare circumstances is it treated by unrelated bone marrow transplant.

Lymphoma

Lymphomas are malignancies of the lymphoid tissue, including the lymph glands and are divided into Hodgkins and Non-Hodgkins disease. Mostly they are treated with chemotherapy and / or autologous bone marrow transplant (this means using the patients own "cleaned up" bone marrow). At present, unrelated bone marrow transplant is reserved for patients with relapsed disease.

Bone marrow failure syndromes

This is characterised by the development of falling blood counts and is caused by the failure of the bone marrow "factory" to produce blood cells. Examples of diseases in this category include Aplastic Anaemia and Diamond Blackfan Anaemia. The former may be congenital as with Fanconi’s Anaemia (AA), a condition associated with growth retardation, congenital defects of the skeleton, kidney and skin. AA may be "acquired" when there is no obvious precipitating cause. More rarely, AA may be the presenting feature of Acute Lymphoblastic or Myeloid Leukaemia and Myelodyplastic Syndrome.

Aplastic anaemia is a rare blood disease (between 120 - 250 new cases are diagnosed in the UK each year) which shares some of the clinical features of leukaemia but progresses quite differently. Its cause is not clear, but the effect of the disease is to prevent the bone marrow from producing circulating red and white blood cells. This leads to anaemia, a tendency to infection and bleeding.

The disease may develop at any time, although it is more common in people in their teenage years, twenties and old age. It develops in both men and women, although it seems to affect slightly more males than females.

Initial treatment focuses on the need to replace blood cells by blood transfusion which helps to prevent the patient acquiring infections. Although it may take several years, some patients recover as a result of this treatment alone. However in severe cases this is unlikely and a second phase of treatment is used to assist the recovery of the bone marrow. It is here that a bone marrow transplant may be recommended.

Diamond Blackfan Anaemia (DBA) is a rare congenital disorder of red blood cell production and in a third of cases may be associated with congenital physical abnormalities such as a sunken bridge of the nose.

Immunodeficiency syndromes

Severe Combined Immunodeficiency (SCID)

This covers a variety of inherited disorders which have in common a combined T and B lymphocyte (white blood cell) deficiency. Although advances have occurred with antibiotic and antivial therapies, the only curative treatment is a bone marrow transplant. In the absence of a family donor an unrelated donor is required.

Wiskott-Aldrich Syndrome (WAS)

This disorder comprises a combination of immunodeficiency, platelet abnormalities and eczematous skin lesions. It is inherited and only affects boys.

Familial Erythophagocytic Lymphohistiocytosis (FEL)

An inherited disorder that is characterised by a defective immune response.

Haemoglobinopathies

Thalassaemia Major

Resulting from a completely absent or severely reduced synthesis of haemoglobin, (the substance in red blood cells which carries oxygen), this inherited condition leads to severe anaemia and the need for regular blood transfusions. The latter can give rise to serious iron overload and subsequent liver and cardiac failure. Currently, related donor marrow transplant is recommended but unrelated donor BMT is not.

Inborn errors of metabolism and other genetic disorders

Bone marrow transplant has been extensively used to treat a wide variety of haematological disorders. More recently, it has been used to treat a group of rare and ultimately lethal metabolic disorders and other genetic diseases, some of which are immediately life-threatening and other of which are associated with progressive disability. These may result form the deficiency of a single enzyme required for a specific metabolic process. Bone marrow transplant is used to provide a source of the deficient enzyme.

Hurlers / Hunters

These are inherited enzyme deficiency which are usually diagnosed in infancy. They have typical facial appearances with progressive mental retardation, multiple bony problems and later cardiac involvement. Death occurs usually in the sufferers first or second decade of life.

Metachromatic leucodystrophy

Again, an inherited enzyme deficiency, but presenting in several clinical forms depending on the age of onset. Mental function, speech and mobility deteriorate at different rates with death a few years after onset in the late infantile form.

Adrenoleucodystrophy

The absence of the enzyme in this disease results in a protracted central nervous system deterioration. It is an inherited condition which usually presents in the first decade of life, with a peak at age seven.

Gauchers disease

This inherited disorder is divided into three clinical subtypes - adult, childhood and infantile forms. There can be cerebral involvement in addition to enlargement of the liver and spleen and the bones may also become pathologically weak, resulting in fractures. A single enzyme missing is agin the underlying cause.

Osteopetrosis

This is a disease of abnormal bone remodelling, so that normal bone marrow cavities do not develop which leads to bone marrow failure. Blindness and deafness may follow due to abnormal pressure of bones on the nerves involved. The severity can vary widely and it is congenital, however, bone marrow transplantation replaces the deficient "remodelling" cells.