Pediatric immune deficiencies: current treatment approaches

To summarize the currently available definitive therapies for patients with inborn errors of immunity (IEIs) with a strong focus on recent advances in allogeneic hematopoietic cell transplantation (HCT) and gene therapy, including the use of alternative donors, graft manipulation techniques, less toxic approaches for pretransplant conditioning and gene transfer using autologous hematopoietic stem cells.

In the absence of a matched sibling or a matched related donor, therapeutic alternatives for patients with IEIs include alternative donor transplantation or autologous gene therapy, which is only available for selected IEIs. In recent years, several groups have published their experience with haploidentical hematopoietic cell transplantation (HHCT) using different T-cell depletion strategies. Overall survival and event free survival results, although variable among centers, are encouraging. Preliminary results from autologous gene therapy trials with safer vectors and low-dose busulfan conditioning have shown reproducible and successful results. Both strategies have become valid therapeutic options for patients with IEIs. A new promising and less toxic conditioning regimen strategy is also discussed.

Definitive therapies for IEIs with HCT and gene therapy are in stage of evolution, not only to refine their efficacy and safety but also their reach to a larger number of patients.