Which diseases can be treated by Bone Marrow Transplants ?

Bone marrow transplants are traditionally associated with leukaemia, but are now considered as treatment for a variety of diseases. These diseases include immune-deficiency illnesses, blood cell production disorders, haematological malignancies, and congenital metabolic disorders.

The success rate of bone marrow transplants is 40-60%, but this rate is improving all the time and is particularly good in children.

Under immune-deficiency illnesses BMT treatment plan could help in
Immunodeficiency syndromes affect the ability of the individual’s immune system to resist infectious disease.

Wiscott-Aldrich Syndrome (WAS)
This syndrome affected Anthony Nolan. The extremely rare disorder comprises a combination of immunodeficiency, platelet abnormalities and eczematous skin lesions. It is inherited and only affects boys.

Severe Combined Immunodeficiency (SCID)
This covers a variety of rare inherited disorders which are characterised by an incomplete, or deficient, immune system, resulting from a deficiency in white blood cells. The symptoms of immune deficiency depend on what part of the immune system is affected and can range from mild to life-threatening. SCID can be successfully treated if it's identified early. Otherwise, it's often fatal within the first year. Although advances have occurred with antibiotic and antiviral therapies, the only curative treatment is a bone marrow transplant.

Aplastic anaemia
This is a rare and extremely serious blood disease, with just 120 - 250 new cases diagnosed in the UK each year. It 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’s ability to produce 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 affects 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. In severe cases this is unlikely and a second phase of treatment is used to assist the bone marrow recovery. It is here that a bone marrow transplant may be recommended.

Diamond Blackfan Anaemia (DBA)
Diamond Blackfan Anaemia is a rare congenital disorder affecting the production of red blood cells and occurs equally in men and women. Around a third of patients have physical abnormalities, often involving malformations of the thumbs, which means that diagnosis is frequently inside the first year.

Under blood cell production disorders BMT treatment plan could help in

Myelodyplastic and Myeloproliferative Syndromes
Myelodysplastic syndromes are a group of malignant disorders characterised by "dysplastic" (ineffective) blood cell production, which progresses 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, the cells which produce collagen fibres. As a result, 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 At present, unrelated bone marrow transplant is reserved for patients with relapsed disease.

Under haematological malignancies BMT treatment plan could help in

Haemoglobinopathies
Haemoglobinopathies are pathological conditions relating to the red blood cells.

Thalassaemia Major
Thalassaemia Major results from a complete absence or severe reduction in the 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, transplant from a related donor is recommended but not from an unrelated donor.

Under congenital metabolic disorders BMT treatment plan could help in

Metabolic and genetic disorders
Bone marrow transplant has been extensively used to treat haematological disorders, but more recently it has been used to treat a group of rare and terminal metabolic disorders and other genetic diseases.

Some of these are immediately life-threatening - others are associated with progressive disability. These may result from 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.

Some examples are given below:

Hurlers / Hunters Syndrome
These are inherited enzyme deficiencies 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 sufferer’s 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.

X-linked Lymphoproliferative Syndrome
XLP, also known as Duncan's Syndrome, causes the immune system to respond abnormally to some viral infections. This can result either in an underactive or overactive immune system, causing many problems.

Why are transplants necessary?
The word transplant suggests the image of a major organ transplant, but bone marrow transplants are very different. Bone marrow and peripheral blood stem cells are both removed by needle - and received intravenously.

The objective of a transplant is to restore the bone marrow’s ability to produce healthy blood cells - to carry oxygen, prevent bleeding and fight off infection.

Some illnesses directly attack the red blood cells. In others, the chemotherapy used to destroy the proliferating cancer cells also destroys the patient’s bone marrow.

For both cases, the transplanted cells – from the bone marrow or the peripheral blood from a volunteer donor - have the potential to restore the bone marrow’s lifesaving ability.

Patient HLA Typing and Unrelated Donor Matching Guidelines

Patient HLA Typing
HLA typing of the patient must be undertaken in a laboratory accredited by the European Federation for Immunogenetics (EFI) or by an Agency with similar standards and accreditation process.

HLA typing of the patient must be undertaken on two occasions using samples drawn at different times, so that the typing and identity is confirmed.

HLA typing of the patient must be by DNA methods, and include at a minimum HLA-A, -B -C and DRB1. This may be supplemented by serology to ascertain protein expression. HLA-DRB3, DRB4, DRB5 and DQB1 typing are considered desirable, and DPB1 optional. The resolution of typing should ideally be high resolution for HLA-A, B and DRB1, resolving polymorphisms within exons 2 and 3 for HLA-A and B and polymorphisms within exon 2 for HLA-DRB1, at a minimum. All serologically defined antigens should be discriminated.

It should be noted that the matching algorithm in operation at the suggested BMT Center in India and Israel  works optimally when patient HLA class I (-A & -B) and class II (-DRB1) alleles are defined to a level of resolution with 4 digits. Low resolution (2 digit) patient typing does not allow the most informative donor listing to be produced. Additionally, low resolution typing can increase the time and cost of the search as this will be conducted using incomplete information.

Patient / Donor Matching

Our board certified BMT Consultant recommends that, when possible, patients and unrelated donors should be matched on high resolution (as described above) HLA-A, -B, -C and -DRB1 types. When such a match is not available, partially matched donors can be released, but all levels of mismatch would be subject to review. The transplant centre may be required to justify their choice of mismatched donor and provide additional information relating to the transplant protocol. Where it is necessary to select a mismatch donor for transplant, the patient and donor typing would be expected to be at high resolution so that the degree of mismatch throughout may be ascertained.

It is expected that the search will be extended internationally, when appropriate, so that the best matching donor can be identified. On the request of the Recipient family or their representatives upon application to Mediescapes India may approach Reports from `Bone Marrow Donors Worldwide’ (BMDW) which are issued for Asian registry at applicable protocol cost estimates .

It should be noted that registries in different countries have their own policies on donor release that may differ from that of The Anthony Nolan Trust.

Final Donor Selection

For final selection of an unrelated donor, HLA typing of both donor and recipient must be repeated using a new typing sample from each such that each individual's typing and identity is confirmed. The final typing of each must be performed in the same laboratory (i.e. the transplant centre laboratory), using the same techniques, and tested within a reasonable timeframe of one another.

Advice on selecting donors for patients can be provided by our associated Hospital. However, the final decision on donor suitability is always the responsibility of the transplant centre.