Faster T-cell development following gene therapy compared to haplo-identical hematopoietic stem cell transplantation in the treatment of SCID-X1.

Fabien Touzot, Despina Moshous, Rita Creidy, Bénédicte Neven, Pierre Frange, Guilhem Cros, Laure Caccavelli, Johanna Blondeau, Alessandra Magnani, Jean-Marc Luby, Brigitte Ternaux, Capucine Picard, Stéphane Blanche, Alain Fischer, Salima Hacein-Bey-Abina and Marina Cavazzana

Key points

  • SCID-X1 patients treated with gene therapy show a faster T cell development as compared to patients treated with haplo-identical HSCT.


During the last decade, gene therapy via ex vivo gene transfer into autologous hematopoietic stem cells has emerged as a convincing therapy for severe combined immunodeficiency caused by ILR2G mutation (SCID-X1) despite the occurrence of genotoxicity caused by the integration of first generation retroviral vectors. However, the place of gene therapy among the therapeutic armamentarium remains to be defined. We retrospectively analyze and compare clinical outcomes and immune reconstitution in 13 consecutive SCID-X1 patients having undergone haploidentical Hematopoietic Stem Cell transplantation (HSCT) and 14 SCID-X1 patients treated with gene therapy over the same period at a single center level, the Necker Children's Hospital (Paris, France). Our results show a clear advantage in terms of T cell development of gene therapy over HSCT with a mismatched donor. Patients treated with gene therapy display a faster T cell reconstitution and a better long-term thymic output. Interestingly, this advantage of gene therapy versus haploidentical HSCT seems to be independent of the existence of clinical graft versus host disease in the latter condition. If data of safety are confirmed over the long term, gene therapy for SCID-X1 appears to be an an equal, if not superior alternative to haplo-identical HSCT.

  • Submitted December 9, 2014.
  • Accepted March 1, 2015.