Treatment of SCID

TREATMENT OF SCID

Hematopoietic Stem Cell Transplantation

Untreated SCID is invariably fatal in early infancy. Once a diagnosis of SCID is confirmed, irrespective of the molecular diagnosis, HSCT from a human leucocyte antigen (HLA-) identical or haplo-identical family donor is the treatment of choice. Treatment of SCID with HSCT before 3.5 months of age results in good immune reconstitution and 95 percent survive long term. Delay in treatment, or the occurrence of infection, impairs outcome. Infection and GvHD are the main complications follow-ing HSCT. North American and European data indicate that long-term survival after transplants from HLA-matched unrelated donors was close to 60 percent. Review of European data between 1968 and 1999 indicates the progressive improvement of outcome, which is mainly because of better prevention of GvHD and the treatment of infection. Analysis of the outcome of European and U.S. bone marrow transplant programs for the treatment of SCID is ongoing and will be regularly reported.

Gene Therapy for SCID

Long-term immune reconstitution has been achieved in patients with SCID caused by the common Î³-chain deficiency or ADA deficiency, using gene therapy.

This was achieved by ex vivo gene transfer to hematopoietic stem cells isolated from the patient’s bone marrow. These gene-reconstituted stem cells were retransfused into the patient. To date, gene therapy has been restricted to patients without an HLA-matched family donor.

Several cases of leukemia have occurred among Î³-chain-deficient patients who received gene therapy. In these cases, the retroviral vector had integrated close to the LMO2 proto-oncogene in the leukemia clone, leading to aberrant transcription and expression of LMO2. Because of this setback, clinical trials of gene therapy for SCID are being carefully evaluated, and more experience is required before the definitive role of gene therapy in SCID is established.

(<1 percent) exhibit profound T lympho-penia, associated with opportunistic infec-tions and a poor outlook unless rescued with fetal thymic transplant.

The cardiac, velopharyngeal, thymic, and parathyroid abnormalities are due to the defective development of third and fourth pharyngeal arches during ontogeny.

The 22q. 11.2 region contains the TBX1 gene, which belongs to the T-BOX fam-ily of genes that incorporate proteins that regulate embryonic development. Patients with mutations in the TBX1 genes also develop the clinical features seen in 22q. 11.2 deletion syndrome, suggesting that haplo-insufficiency of the TBX1 gene may be responsible for the clinical features seen in those with a deletion of the 22q. 11.2 region