Emerging Targets for Hematopoietic Cell Transplantation (HCT): Genetic Disorders of Hematopoiesis and Immunity

This review highlights the potential benefits and challenges of the application of Hematopoietic Cell Therapy (HCT) to the treatment of three rare genetic conditions affecting immunohematopoiesis early in life: IPEX (Immune dysregulation, Polyendocrinopathy, X-linked), ALPS (Autoimmune Lymphoproliferative s.), and Dyskeratosis Congenita (DC). Each of these conditions can result from several distinct genetic defects with somewhat distinct clinical prognoses. Severe, life-threatening, autoimmune complications are seen with IPEX and ALPS. In the DC disorders, marrow failure is a common abnormality. ALPS and DC are associated with increased risk of hematopoietic malignancy. Early experience with HCT in these disorders predict that most of the life-threatening complications of these conditions are reversible and/or preventable by HCT. In the current era, it is advised that affected patients undergo definitive genetic diagnosis, and be considered for reduced intensity HCT when young and relatively healthy.