bone marrow were reported which permit the use of haploldentical (l.e., 
parental) bone marrow In the transplantation of children with SCID without the 
development of lethal GVHD. Again, these new transplant methods have been very 
successful In the treatment of ADA (+) SCID patients, whereas the results of T 
cell-depleted marrow grafts in patients with ADA(-)SCID have been 
disappointing. Survival with stable engraftment and Immune reconstitution has 
been seen in 56% of patients transplanted for ADA(+) forms of SCID. but only In 
31% of ADA(-) SCID patients. A major problem encountered In these patients has 
been graft failure or rejection. A proportion have failed to engraft despite 
multiple transplants. In addition, at least three patients have developed 
chlmerlsm initially only to lose the graft several months later without ever 
reconstituting Immunity. Recently, some success in this form of 
transplantation for ADA(-)SCID has been achieved when the patients were 
prepared by aggressive pretransplant myeloablation with total body Irradiation 
or with busulfan used in conjunction with cyclophosphamide. The addition of 
this more aggressive patient preparation has the potential for significant long 
term toxicity to the lungs and GI tract as well as increased toxicity in the 
immediate peri-transplant period itself. At least one ADA(-)SCID patient has 
died of cyclophosphamide cardiomyopathy associated with this more aggressive 
regimen. 
Another approach to treatment of ADA deficiency has been enzyme 
replacement. Since the ADA substrates are in almost total equilibrium with the 
toxic phosphorylated metabolites trapped in the cell, removal of the 
extracellular substrates will lower the intracellular concentration of both the 
substrates and their metabolites. Initially, patients were treated by partial 
exchange transfusion to provide ADA-containing normal (irradiated) red blood 
cells as a source of detoxifying enzyme. Several patients had a lowering of 
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Recombinant DNA Research, Volume 12 
