of the disease just as a matched bone marrow transplantation does. Partial 
corrections may also occur if only a limited number of immune cells are 
converted to normal. Some manifestations, such as compromised lung capacity 
due to repeated pulmonary infections prior to gene therapy, may not be 
reversibl e. 
4. What alternative therapies exist? In what groups of patients are 
these therapies effective? What are their relative advantages and 
dlsadvanages as compared with the proposed gene therapy? 
The development of effective therapy for SCID has been a major area of 
challenge for clinical medicine and an area of significant Innovation. Bone 
marrow transplantation (BMT) from an HLA-compatibl e donor was Introduced 
clinically In 1968. initially as a treatment for SCID. In 1975 the first 
successful treatment of an ADA-deflciency SCID patient by BMT was reported. 
The International experience with HLA-identlcal BMT for SCID has shown an 
overall success rate of approximately 75%. Reconstitution of patients with 
ADA(-)SCID by HLA-identlcal BMT has been excellent overall, but these patients 
more frequently require repeated transplantation for stable reconstitution than 
do children with ADA(+) SCID . HLA-identical sibling donor BMT is the treatment 
of choice for ADA deficiency, and gene therapy would not be considered if this 
option were available. 
Unfortunately, only 25-30% of patients with ADA deficiency have an 
HLA-identical sibling donor. Unmodified BMT from HLA-unmatched donors has 
regularly resulted in lethal graft-versus-host disease (GVHD) and has been 
abandoned. Attempts at transplanting fetal lympho-hematopoietic cells such as 
liver or thymus to treat SCID rarely have been successful and also have been 
abandoned as treatment options. In 1983 methods for depleting T cells from 
Recombinant DNA Research, Volume 12 
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