The first ever successful transplant for SCID was performed in 1968.
Gene therapy offers a cure for two specific forms of SCID and, although other SCID forms may become amenable to this form of treatment in the future, it is likely that HSCT will continue to be the mainstay of treatment of the majority of SCID patients. The severity of the clinical and immunologic phenotype requires prompt intervention, and for most patients, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT). 1 The genetic defects in approximately 90% of the different forms of SCID have now been identified and, despite genetic heterogeneity, all patients are characterized by abnormalities of thymopoiesis and T-cell maturation and function. Affected infants present in the first few months of life with severe, recurrent, and opportunistic infections, and without definitive treatment, the condition is invariably fatal. Severe combined immunodeficiencies (SCIDs) are a genetically heterogeneous group of inherited defects characterized by severe abnormalities of immune system development and function. These developments together with the advent of universal newborn screening for SCID should allow for a highly favorable outcome for this otherwise lethal condition. The development of autologous hematopoietic stem cell gene therapy provides another treatment of the X-linked and adenosine deaminase–deficient forms of SCID, and we discuss how we have integrated gene therapy into our treatment strategy. We aim to use matched related and unrelated donors (including cord blood) whenever possible and have limited the use of mismatched haploidentical donors. Wherever possible, we attempt to transplant SCID patients without the use of cytoreductive conditioning, but it is clear that this is only successful for specific SCID forms and, although survival is good, in specific patients there are ongoing humoral defects. Advances in understanding the genetic basis of disease also mean that we increasingly tailor transplant protocols to the specific SCID form. Numerous multicenter studies have identified the factors determining successful outcome, and survival for SCID has shown great improvement. Allogeneic hematopoietic stem cell transplantation is an extremely effective way of restoring immunity in these individuals. Severe combined immunodeficiency (SCID) arises from different genetic defects associated with lymphocyte development and function and presents with severe infections.
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