Hematopoietic stem cell transplant Treatment of<unk>  depends on the severity of the disease. WAS is primarily a disorder of the blood-forming tissues, so in cases of severe disease (WAS score 3–5) the only widely available curative treatment currently available is a hematopoietic stem cell transplant (HCT). In this procedure stem cells are harvested from umbilical cord blood, bone marrow, or peripheral blood following treatment with medications that cause stem cells to leave the bone marrow and circulate systemically. The best outcomes are with HLA-identical or similar donors (often siblings). In cases of milder disease the potential benefits of HCT (>90% probability of cure if transplant occurs before age two) must be considered in the context of non-trivial risks presented by the procedure itself and the potential need for lifelong immunosuppression to prevent graft-versus-host disease. Generally outcomes are better if HCT occurs prior to the development of autoimmune disease or malignancy, however there are risks associated with chemotherapy (needed to make room for the new stem cells) especially in young infants (risk of a second cancer, or infertility). Bleeding complications Otherwise WAS treatment is focused on managing symptoms and preventing complications. The greatest mortality risk in WAS before age 30 is from bleeding so aspirin and other nonsteroidal anti-inflammatory drugs that may interfere with already compromised platelet function should generally be avoided. Circumcision, as well as elective surgeries, should generally be deferred in males with thrombocytopenia until after HCT if possible. Protective helmets can help protect children from life-threatening intracranial hemorrhage (brain bleed) which could result from head injuries. Patients may require platelet transfusions when there is extreme bloodloss (such as during surgery) or for very low platelets splenectomy (removal of the spleen) may also be lifesaving. However, splenectomy is generally considered palliative and is not universally recommended in WAS because it can increase the risk of life-threatening infections. Post-splenectomy patients will require lifelong antibiotic prophyllaxis to prevent infections. Study of eltrombopag, a thrombopoietic agent used to increase platelets in immune thrombocytopenic purpura (ITP), in WAS concluded that although it increased platelet numbers it failed to increase platelet activation in most patients. It has since been proposed the eltrombopag may be used to bridge to HCT in patients with severe thrombocytopenia to normalize platelet numbers without transfusions and decrease bleeding events. Anemia from bleeding may require iron supplementation or blood transfusion. Regular surveillance of blood counts is recommended. Infections and autoimmune disease For patients with frequent infections, intravenous immunoglobulins (IVIG) or subcutaneous immunoglobulins can be regularly scheduled to boost the immune system. Adequacy of IVIG replacement can be assessed via periodic lab draws. WAS patients with immune system compromise may benefit from antibiotic prophylaxis, for example by taking trimethoprim-sulfamethoxazole to prevent Pneumocystis jirovecii-related pneumonia. Similarly, prophylactic antibiotic use may also be considered in patients with recurrent bacterial sinus or lung infections. When there are signs or symptoms of an infection, prompt and thorough evaluation is important including blood cultures to guide therapy (often IV antibiotics). Live vaccines (such as MMR or rotavirus) should be avoided during routine childhood vaccination. Inactivated vaccines may be given safely but may not provide protective levels of immunity. Eczema is generally treated with topical steroids, and if chronic skin infections exacerbate eczema an antibiotic may also be given. Autoimmune disease is managed with judicious use of appropriate immunosuppressants. Gene therapy For severely affected males without an HLA-matched donor, studies of correcting<unk>  with gene therapy using a lentivirus are underway. Proof-of-principle for successful hematopoietic stem cell gene therapy has been provided for patients with<unk> . In July 2013 the Italian San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) reported that three children with<unk>  showed significant improvement (improved platelet counts, immune functiona, and clinical symptoms) 20–30 months after being treated with a genetically modified lentivirus. In April 2015 results from a follow-up British and French trial six out of seven individuals showed improvement of immune function and clinical symptoms an average of 27 months after treatment with gene therapy. Importantly, neither study showed evidence of leukemic proliferation following treatment, a complication of early attempts at gene therapy using a retroviral vector. It is unknown why these gene therapies did not restore normal platelet numbers, but gene therapy treatment was still associated with transfusion-independence and a significant reduction in bleeding events. A version of this treatment, OTL-103, is being developed by Orchard Therapeutics and () is undergoing Phase I/II clinical trials.
Wiskott–Aldrich syndrome
Common variable immunodeficiency
Chronic granulomatous disease
Severe combined immunodeficiency
SAPHO syndrome
Hyper-IgM syndrome type 5
Ataxia–telangiectasia
Hyper-IgM syndrome type 2