Bone marrow transplantation (BMT) is\u00a0a cure for many primary immunodeficiency (PID) conditions. In the last 20 years there have been\u00a0huge advances in\u00a0success and survival rates and in the range of conditions that can be treated by BMT.<\/p>\n
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 \u2018stem cells\u2019. 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.<\/p>\n
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 \u2018tissue type\u2019 as them and is therefore called a \u2018match\u2019. 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.\u00a0Occasionally, a less well matched (mis-matched) donor may be considered.<\/p>\n
In order to allow for these new cells to grow and develop the patient has to undergo \u2018conditioning\u2019. This involves giving several powerful medicines called chemotherapy, which work in two ways:<\/p>\n
In some forms of SCID, transplant can be undertaken without conditioning.<\/p>\n
Having a BMT involves a long stay in hospital (on average 6\u20138 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\u2019s immune system is low and a few extra precautions are necessary to protect them from infection.<\/p>\n
Over the last few years there has been slow and steady, but significant, progress in BMT techniques, and recent results for PIDs are\u00a0extremely good. Survival and cure are now equivalent with either a matched sibling or a well-matched unrelated donor and reach 85\u201390 per cent\u00a0in specialist centres designated to transplant PID patients.<\/p>\n
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.<\/p>\n
The main risks are infection and graft-versus-host disease (GvHD). In GvHD the new bone marrow from the donor may recognise the patient\u2019s cells as \u2018foreign\u2019 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\u20136 months for the new immune system to grow and function properly and during that time, prophylactic antibiotics and immunoglobulin will need to be taken.<\/p>\n
Doctors\u00a0have made some general recommendations about BMT for PIDs. <\/strong>These are:<\/p>\n You should discuss the suitability and individual risk factors for you and your family with doctors and nurses involved in your care.<\/p>\n Finally, it is important to remember that although a person\u2019s PID may be cured by BMT, the inheritance issues of passing their condition to future offspring\u00a0remain.<\/p>\n 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.<\/p>\n IL2RG (Common Gamma Chain, X-linked)<\/p>\n JAK3<\/p>\n IL7Ralpha<\/p>\n CD45<\/p>\n CD3 antigen delta subunit deficiency (CD3D)<\/p>\n CD3 antigen epsilon subunit deficiency (CD3E)<\/p>\n CD3 antigen zeta subunit deficiency (CD3 Z)<\/p>\n Coronin 1A<\/p>\n RAG1<\/p>\n RAG2<\/p>\n Artemis<\/p>\n DNAPKcs<\/p>\n ADA<\/p>\n AK2<\/p>\n Omenn syndrome<\/p>\n DNA ligase IV deficiency<\/p>\n Cernunnos deficiency<\/p>\n CD40 ligand deficiency (CD154)<\/a><\/p>\n CD3 antigen gamma subunit deficiency (CD3G)<\/p>\n CD8 antigen deficiency<\/p>\n ZAP70 deficiency<\/p>\n PNP<\/p>\n CD40<\/a><\/p>\n ORAI 1<\/p>\n STIM 1<\/p>\n RAG 1 (leaky phenotypes)<\/p>\n Artemis<\/p>\n ITK deficiency<\/p>\n Regulatory factor X ankyrin-repeat containing (RFXANK)<\/p>\n Major histocompatibility complex class II transactivator (MHC2TA)<\/p>\n Regulatory factor X-associated protein (RFXAP)<\/p>\n Regulatory factor X 5 (RFX5)<\/p>\n Other T-cell deficiency<\/strong><\/p>\n DOCK8 deficiency<\/p>\n STAT5b deficiency<\/p>\n Omenn syndrome (due to)<\/strong><\/p>\n RAG1<\/p>\n RAG2<\/p>\n Artemis<\/p>\n RMRP<\/p>\n ADA<\/p>\n Gamma C (X-linked)<\/p>\n CD45<\/p>\n IL7Ralpha<\/p>\n DNA ligase IV deficiency<\/p>\n Familial hemophagocytic lymphohistiocytosis syndrome (FHLH)<\/p>\n Perforin 1 deficiency (PRF1)<\/p>\n Munc 13.4 deficiency (UNC 13D)<\/p>\n Syntaxin 11 deficiency<\/p>\n Munc 18.2 deficiency (STXBP2)<\/p>\n Immunodeficiency with hypopigmentation<\/strong><\/p>\n Chediak\u2013Higashi syndrome<\/p>\n Griscelli syndrome<\/p>\n Hermansky\u2013Pudlak syndrome, type 2<\/p>\n X-linked lymphoproliferative syndrome<\/p>\n IPEX<\/strong><\/p>\n Foxp3 deficiency<\/p>\n CD25 deficiency<\/strong><\/p>\n Early-onset inflammatory bowel disease (IL10R deficiency)<\/strong><\/p>\n IL10R alpha<\/p>\n IL10R beta<\/p>\n Wiskott\u2013Aldrich syndrome (WAS)<\/a><\/p>\n Cartilage hair hypoplasia<\/p>\n Chronic mucocutaneous candidiasis (CMC)<\/p>\n Congenital dyskeratosis (some forms)<\/p>\n Immunodeficiency centromeric instability facial anomalies syndrome (ICF)<\/p>\n Schimke disease<\/p>\n Hyper IgE syndrome – autosomal dominant (STAT 3 deficiency)<\/a><\/p>\n\n
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Conditions that can be treated by BMT<\/h3>\n
Severe combined immunodeficiency (SCID)<\/strong><\/h3>\n
Combined immunodeficiency (CID)<\/strong><\/h3>\n
HLA class II deficiency<\/strong><\/h3>\n
Diseases of immune dysregulation<\/strong><\/h3>\n
Other well-defined PIDs<\/h3>\n