Bone marrow transplantation (BMT) is a cure for many primary immunodeficiency (PID) conditions. In the last 20 years there have been huge advances in success and survival rates and in the range of conditions that can be treated by BMT.
What is bone marrow?
Bone marrow is the soft, spongy tissue found in the centre of bones. It is responsible for producing the three main types of blood cells: red blood cells, white blood cells (cells of the immune system) and platelets. All of these start off as immature cells called ‘stem cells’. These cells mature in the bone marrow and are then slowly released into the bloodstream. A bone marrow or stem cell transplant involves collecting healthy cells from a matched donor and introducing them into the person with a PID. These new healthy stem cells then start to make fully functional white blood cells that are capable of fighting infection.
What is involved?
The person with a PID receives bone marrow (or sometimes stem cells collected from the umbilical cord blood of babies are used) from a donor who shares the same ‘tissue type’ as them and is therefore called a ‘match’. Two types of match are normally considered: a perfectly matched related donor (this is usually a brother or a sister) or a well-matched unrelated donor. Occasionally, a less well matched (mis-matched) donor may be considered.
In order to allow for these new cells to grow and develop the patient has to undergo ‘conditioning’. This involves giving several powerful medicines called chemotherapy, which work in two ways:
- to make space for the new stem cells
- to suppress the immune system in order to encourage acceptance of the new cells.
In some forms of SCID, transplant can be undertaken without conditioning.
How long does it take?
Having a BMT involves a long stay in hospital (on average 6–8 weeks, although it may be longer), during which time the patient is looked after in an isolation room on a transplant ward. This ward will have more restrictions on visiting, diet and hygiene than a general ward. This is because during a transplant the patient’s immune system is low and a few extra precautions are necessary to protect them from infection.
Over the last few years there has been slow and steady, but significant, progress in BMT techniques, and recent results for PIDs are extremely good. Survival and cure are now equivalent with either a matched sibling or a well-matched unrelated donor and reach 85–90 per cent in specialist centres designated to transplant PID patients.
Whilst transplantation is generally best tolerated in childhood, successful outcomes are now possible in young people and adults using new transplantation techniques. However, BMT is not without risk.
What are the risks?
The main risks are infection and graft-versus-host disease (GvHD). In GvHD the new bone marrow from the donor may recognise the patient’s cells as ‘foreign’ to it and react against them. GvHD can cause problems with the skin, liver and bowels. Also, immediately after the BMT, the patient remains very immunodeficient and susceptible to infection. It may take 4–6 months for the new immune system to grow and function properly and during that time, prophylactic antibiotics and immunoglobulin will need to be taken.
Doctors have made some general recommendations about BMT for PIDs. These are:
- BMT should start to be considered soon after a diagnosis of a PID. This is because better outcomes are usually achieved if those affected do not have a history of serious infections or inflammatory problems. This means that doctors will want to test siblings to see if they are a tissue match. If siblings are not a tissue match, then doctors can start to find a well-matched unrelated donor. The doctors are also then able to give appropriate counselling over a period of time to help people make this important decision once a suitable donor is found.
- BMT should be done in a specialist centre that has experience of transplanting people with a PID. This is because the doctors will know about the specific PID and be able to give good-quality up-to-date advice about risks and benefits.
You should discuss the suitability and individual risk factors for you and your family with doctors and nurses involved in your care.
Finally, it is important to remember that although a person’s PID may be cured by BMT, the inheritance issues of passing their condition to future offspring remain.
Conditions that can be treated by BMT
Here is a list of type of PID that could be treated by BMT. The list includes the most common indications but is by no means exhaustive and other specific PIDs may be suitable for transplantation.
Severe combined immunodeficiency (SCID)
- IL2RG (Common Gamma Chain, X-linked)
- CD3 antigen delta subunit deficiency (CD3D)
- CD3 antigen epsilon subunit deficiency (CD3E)
- CD3 antigen zeta subunit deficiency (CD3 Z)
- Coronin 1A
Combined immunodeficiency (CID)
- Omenn syndrome
- DNA ligase IV deficiency
- Cernunnos deficiency
- CD40 ligand deficiency (CD154)
- CD3 antigen gamma subunit deficiency (CD3G)
- CD8 antigen deficiency
- ZAP70 deficiency
- ORAI 1
- STIM 1
- RAG 1 (leaky phenotypes)
- ITK deficiency
HLA class II deficiency
- Regulatory factor X ankyrin-repeat containing (RFXANK)
- Major histocompatibility complex class II transactivator (MHC2TA)
- Regulatory factor X-associated protein (RFXAP)
- Regulatory factor X 5 (RFX5)
Other T-cell deficiency
- DOCK8 deficiency
- STAT5b deficiency
Omenn syndrome (due to)
- Gamma C (X-linked)
- DNA ligase IV deficiency
Diseases of immune dysregulation
- Familial hemophagocytic lymphohistiocytosis syndrome (FHLH)
- Perforin 1 deficiency (PRF1)
- Munc 13.4 deficiency (UNC 13D)
- Syntaxin 11 deficiency
- Munc 18.2 deficiency (STXBP2)
Immunodeficiency with hypopigmentation
- Chediak–Higashi syndrome
- Griscelli syndrome
- Hermansky–Pudlak syndrome, type 2
- X-linked lymphoproliferative syndrome
Early-onset inflammatory bowel disease (IL10R deficiency)
Other well-defined PIDs
Wiskott–Aldrich syndrome (WAS)
- Cartilage hair hypoplasia
- Chronic mucocutaneous candidiasis (CMC)
- Congenital dyskeratosis (some forms)
- Immunodeficiency centromeric instability facial anomalies syndrome (ICF)
- Schimke disease
Hyper IgE syndrome – autosomal dominant (STAT 3 deficiency)
Hyper IgE syndrome – autosomal recessive
- Severe congenital neutropenia
- Leukocyte adhesion deficiency (LAD)
- Shwachman–Diamond syndrome
- Chronic granulomatous disease (CGD)
Frequently asked questions