Efficacy and safety of gene therapy in pediatric patients with Fanconi anemia: a systematic review.

INTRODUCTION

Fanconi anemia is a genetic disorder characterized by high risk of hematological and oncological disease. The aim of this review was to summarize the evidence on the safety and efficacy of gene therapy in pediatric patients with Fanconi anemia.

METHODS

Systematic review (PROSPERO registration record CRD420251152704). We searched PubMed/MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, ICTRP, and CENTRAL. The study outcomes included safety, engraftment and persistence, and hematologic outcomes. The risk of bias was assessed with the RoB 2 tool.

RESULTS

The review included seven studies, all conducted in patients with FANCA variants, that evaluated autologous hematopoietic stem cell-based gene therapy from mobilization and collection to lentiviral transduction and reinfusion without conditioning. Safety profile: favorable, with no serious adverse events attributable to the vector/cells and no evidence of lentiviral replication, clonal dominance, or genotoxicity in follow-up periods of up to 7 years. Engraftment/persistence: detectable vector copy numbers and stable polyclonal patterns, more durable engraftment with higher cell doses. Hematological outcomes: stabilization/improvement of cytopenia; transfusion independence in some patients and deferral of bone marrow transplantation. The efficacy of gene therapy was greater in younger patients and in those without advanced bone marrow failure. The overall risk of bias was high.

CONCLUSIONS

Gene therapy showed a favorable safety profile, with no serious adverse events or evidence of genotoxicity. Efficacy was greater in younger children, in those without advanced marrow failure, and with higher doses of corrected CD34+ cells. However, as the included studies were phase I/II trials, the results should be interpreted cautiously; nevertheless, gene therapy appears to be a promising and safe treatment option in the early stages of the disease.