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Efficacy of gene therapy for X-linked severe combined immunodeficiency.
N Engl J Med. 2010 Jul 22; 363(4):355-64.NEJM

Abstract

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 gamma chain.

METHODS

The nine patients, who lacked an HLA-identical donor, underwent ex vivo retrovirus-mediated transfer of gamma 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.)

Authors+Show Affiliations

Department of Biotherapy, Necker-Enfants Malades Hospital, Paris, France. salima.hacein-bey@nck.ap-hop-paris.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20660403

Citation

Hacein-Bey-Abina, Salima, et al. "Efficacy of Gene Therapy for X-linked Severe Combined Immunodeficiency." The New England Journal of Medicine, vol. 363, no. 4, 2010, pp. 355-64.
Hacein-Bey-Abina S, Hauer J, Lim A, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010;363(4):355-64.
Hacein-Bey-Abina, S., Hauer, J., Lim, A., Picard, C., Wang, G. P., Berry, C. C., Martinache, C., Rieux-Laucat, F., Latour, S., Belohradsky, B. H., Leiva, L., Sorensen, R., Debré, M., Casanova, J. L., Blanche, S., Durandy, A., Bushman, F. D., Fischer, A., & Cavazzana-Calvo, M. (2010). Efficacy of gene therapy for X-linked severe combined immunodeficiency. The New England Journal of Medicine, 363(4), 355-64. https://doi.org/10.1056/NEJMoa1000164
Hacein-Bey-Abina S, et al. Efficacy of Gene Therapy for X-linked Severe Combined Immunodeficiency. N Engl J Med. 2010 Jul 22;363(4):355-64. PubMed PMID: 20660403.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of gene therapy for X-linked severe combined immunodeficiency. AU - Hacein-Bey-Abina,Salima, AU - Hauer,Julia, AU - Lim,Annick, AU - Picard,Capucine, AU - Wang,Gary P, AU - Berry,Charles C, AU - Martinache,Chantal, AU - Rieux-Laucat,Frédéric, AU - Latour,Sylvain, AU - Belohradsky,Bernd H, AU - Leiva,Lily, AU - Sorensen,Ricardo, AU - Debré,Marianne, AU - Casanova,Jean Laurent, AU - Blanche,Stephane, AU - Durandy,Anne, AU - Bushman,Frederic D, AU - Fischer,Alain, AU - Cavazzana-Calvo,Marina, PY - 2010/7/28/entrez PY - 2010/7/28/pubmed PY - 2010/8/6/medline SP - 355 EP - 64 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 363 IS - 4 N2 - 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 gamma chain. METHODS: The nine patients, who lacked an HLA-identical donor, underwent ex vivo retrovirus-mediated transfer of gamma 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.) SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/20660403/Efficacy_of_gene_therapy_for_X_linked_severe_combined_immunodeficiency_ L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa1000164?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -