[HTML][HTML] Efficacy of gene therapy for X-linked severe combined immunodeficiency

S Hacein-Bey-Abina, J Hauer, A Lim… - … England Journal of …, 2010 - Mass Medical Soc
S Hacein-Bey-Abina, J Hauer, A Lim, C Picard, GP Wang, CC Berry, C Martinache…
New England Journal of Medicine, 2010Mass Medical Soc
Background The outcomes of gene therapy to correct congenital immunodeficiencies are
unknown. We reviewed long-term outcomes after gene therapy in nine patients with X-linked
severe combined immunodeficiency (SCID-X1), which is characterized by the absence of
the cytokine receptor common γ chain. Methods The nine patients, who lacked an HLA-
identical donor, underwent ex vivo retrovirus-mediated transfer of γ chain to autologous
CD34+ bone marrow cells between 1999 and 2002. We assessed clinical events and …
Background
The outcomes of gene therapy to correct congenital immunodeficiencies are unknown. We reviewed long-term outcomes after gene therapy in nine patients with X-linked severe combined immunodeficiency (SCID-X1), which is characterized by the absence of the cytokine receptor common γ chain.
Methods
The nine patients, who lacked an HLA-identical donor, underwent ex vivo retrovirus-mediated transfer of γ chain to autologous CD34+ bone marrow cells between 1999 and 2002. We assessed clinical events and immune function on long-term follow-up.
Results
Eight patients were alive after a median follow-up period of 9 years (range, 8 to 11). Gene therapy was initially successful at correcting immune dysfunction in eight of the nine patients. However, acute leukemia developed in four patients, and one died. Transduced T cells were detected for up to 10.7 years after gene therapy. Seven patients, including the three survivors of leukemia, had sustained immune reconstitution; three patients required immunoglobulin-replacement therapy. Sustained thymopoiesis was established by the persistent presence of naive T cells, even after chemotherapy in three patients. The T-cell−receptor repertoire was diverse in all patients. Transduced B cells were not detected. Correction of the immunodeficiency improved the patients' health.
Conclusions
After nearly 10 years of follow-up, gene therapy was shown to have corrected the immunodeficiency associated with SCID-X1. Gene therapy may be an option for patients who do not have an HLA-identical donor for hematopoietic stem-cell transplantation and for whom the risks are deemed acceptable. This treatment is associated with a risk of acute leukemia. (Funded by INSERM and others.)
The New England Journal Of Medicine