Issue: July 10, 2015
July 10, 2015
2 min read

Gene therapy superior to haploidentical HSCT for SCID-X1

Issue: July 10, 2015
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Gene therapy was associated with faster T-cell reconstitution and a better long-term thymic output than partially matched hematopoietic stem cell transplantation for children with X-linked severe combined immunodeficiency, according to study results.

“Over the last decade, gene therapy has emerged as a viable alternative to a partial matched stem cell transplant for infants with SCID-X1,” Fabien Touzot, MD, PhD, of Necker Children’s Hospital in Paris, said in a press release. “To ensure that we are providing the best alternative therapy possible, we wanted to compare outcomes among infants treated with gene therapy and infants receiving partial matched transplants.”

SCID-X1 — colloquially known as “bubble boy disease” — is a genetic disorder that prevents children from developing a normally functioning immune system. Treatment options include HSCT from either a fully matched or partially matched donor, or genetic therapy that utilizes the child’s own bone marrow, according to study background.

Touzot and colleagues evaluated data from 27 children (median age, 7 months; range, 1-15 months) treated for SCID-X1 between 1999 and 2013. All patients lacked an appropriate donor for fully matched HSCT.

Fourteen of the patients did not have a partially matched donor and underwent gene therapy, which involved extracting bone marrow, altering the genetic material and transfusing the corrected marrow. The remaining patients (n = 13) with partially matched donors underwent haploidentical HSCT.

Median follow-up was 12 years for gene therapy patients and 6 years for haploidentical HSCT patients.

Researchers observed faster T-cell reconstitution in patients who underwent gene therapy. Eleven patients (78%) who received gene therapy achieved a normal T-cell count after 6 months vs. four patients (26%) who underwent haploidentical HSCT. Significantly higher CD3, CD4 and CD8 cell counts also were seen 6 and 12 months after gene therapy compared with haploidentical HSCT.

Patients who received gene therapy displayed a significantly higher thymic output of CD4+ T lymphocytes, which remained significantly higher 5 years after treatment (P = .03).

Although natural killer (NK)-cell reconstitution failed to occur in both groups, patients in the gene therapy group achieved higher NK-cell counts compared with patients who underwent haploidentical HSCT. This difference was significant at 12 months (P = .01) and 24 months (P = .009).

No patients achieved normal B-cell function. However, immunoglobulin M levels at 24 months were higher among the gene therapy group (median: 1.05 g/L; range, 0.35-4.3 g/L) than the HSCT group (median: 0.42 g/L; range, 0.06-1.89 g/L; P = .0151).

Three patients required hospitalization due to infections in the gene therapy group, whereas five patients experienced 15 infections requiring hospitalization in the HSCT group. The most common infections in the gene therapy group were bacille Calmette-Guérin infection (n = 2) and bacterial pneumonia (n = 1). Patients with infections in the HSCT group experienced fever (n = 3), viral gastroenteritis (n = 2), sepsis (n =4), bacterial pneumonia (n = 1) and bacille Calmette-Guérin infection (n = 5). Gene therapy was associated with shorter length of hospitalization (P = .001).

“Our analysis suggests that gene therapy can put these incredibly sick children on the road to defending themselves against infection faster than a half-matched transplant,” Touzot said. “These results suggest that for patients without a fully matched stem cell donor, gene therapy is the next best approach.” – by Cameron Kelsall


Touzot F, et al. Blood. 2015;doi:10.1182/blood-2014-12-616003.

Disclosure: The researchers report no relevant financial disclosures.