Late effects following hematopoietic cell transplantation for severe combined immunodeficiency: critical factors and therapeutic options.

Introduction: Severe combined immunodeficiency (SCID) is an inborn error of immunity that is fatal without hematopoietic cell transplantation (HCT) or gene therapy (GT). Survival outcomes have improved, largely due to implementation of SCID newborn screening. A better understanding of the long-term outcomes and late effects to address critical aspects of monitoring immune and general health life-long is needed.

Areas covered: In a comprehensive review of PubMed indexed articles with publication dates 2008-2024 we describe the current knowledge of chronic and late effects (CLE) of HCT survivors for SCID as well as the role of GT and advances for specific SCID genotypes. We review factors affecting the development of CLE including disease related factors (genotype, trigger for diagnosis and presence of infection prior to HCT), transplant related factors (type of donor, conditioning regimen, immune reconstitution and graft versus host disease (GVHD) and describe causes and factors associated with higher risk for late mortality in this unique population. We further describe monitoring and potential therapeutic strategies for management of common CLE in this patient population.

Expert opinion: Ongoing research efforts are needed to better describe CLE in survivors, to develop prospective clinical trials aimed at mitigating these CLE, and developing genotype-based approaches for management and follow-up of these patients.