Treating inherited bone marrow failure syndromes and primary immunodeficiency diseases

Inherited bone marrow failure syndromes (IBMFS) are caused by genetic mutations at loci associated with DNA repair, telomere maintenance, and ribosome function. Hematopoietic stem cell transplantation (HSCT) can result in a permanent cure in transfusion-dependent patients if reduced-intensity conditioning and long-term screening for relapse can be successfully implemented. Primary immunodeficiency diseases (PIDs) arise from inborn errors of the host immune system and affected patients must protect themselves against intractable infections and immune system dysregulation. HSCT is curative in many pediatric patients; however, specific immunomodulatory therapies are now available for controlling autoimmune and/or autoinflammatory diseases. Advanced clinical sequencing technologies have continued to identify novel monogenic diseases that share the phenotype of hematological and immunological abnormalities, along with adult cases of IBMFS and/or PIDs. Importantly, genetic counseling is required for carrier detection while selecting sibling donors for HSCT. Here, we describe treatment strategies for IBMFS and/or PIDs and associated pitfalls.