New to MyHealth?
Manage Your Care From Anywhere.
Access your health information from any device with MyHealth. You can message your clinic, view lab results, schedule an appointment, and pay your bill.
ALREADY HAVE AN ACCESS CODE?
DON'T HAVE AN ACCESS CODE?
NEED MORE DETAILS?
MyHealth for Mobile
Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency
Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency BLOOD Cicalese, M. P., Ferrua, F., Castagnaro, L., Pajno, R., Barzaghi, F., Giannelli, S., Dionisio, F., Brigida, I., Bonopane, M., Casiraghi, M., Tabucchi, A., Carlucci, F., Grunebaum, E., Adeli, M., Bredius, R. G., Puck, J. M., Stepensky, P., Tezcan, I., Rolfe, K., De Boever, E., Reinhardt, R. R., Appleby, J., Ciceri, F., Roncarolo, M. G., Aiuti, A. 2016; 128 (1): 45-54Abstract
Adenosine deaminase (ADA) deficiency is a rare, autosomal-recessive systemic metabolic disease characterized by severe combined immunodeficiency (SCID). The treatment of choice for ADA-deficient SCID (ADA-SCID) is hematopoietic stem cell transplant from an HLA-matched sibling donor, although <25% of patients have such a donor available. Enzyme replacement therapy (ERT) partially and temporarily relieves immunodeficiency. We investigated the medium-term outcome of gene therapy (GT) in 18 patients with ADA-SCID for whom an HLA-identical family donor was not available; most were not responding well to ERT. Patients were treated with an autologous CD34(+)-enriched cell fraction that contained CD34(+) cells transduced with a retroviral vector encoding the human ADA complementary DNA sequence (GSK2696273) as part of single-arm, open-label studies or compassionate use programs. Overall survival was 100% over 2.3 to 13.4 years (median, 6.9 years). Gene-modified cells were stably present in multiple lineages throughout follow up. GT resulted in a sustained reduction in the severe infection rate from 1.17 events per person-year to 0.17 events per person-year (n = 17, patient 1 data not available). Immune reconstitution was demonstrated by normalization of T-cell subsets (CD3(+), CD4(+), and CD8(+)), evidence of thymopoiesis, and sustained T-cell proliferative capacity. B-cell function was evidenced by immunoglobulin production, decreased intravenous immunoglobulin use, and antibody response after vaccination. All 18 patients reported infections as adverse events; infections of respiratory and gastrointestinal tracts were reported most frequently. No events indicative of leukemic transformation were reported. Trial details were registered at www.clinicaltrials.gov as #NCT00598481.
View details for DOI 10.1182/blood-2016-01-688226
View details for Web of Science ID 000379249600012
View details for PubMedID 27129325