SCID Bu/Flu/ATG Study With T Cell Depletion

Inclusion Criteria:

• All patients with SCID who lack a histocompatible sibling or HLA-matched related donor will be considered as candidates for this study protocol.

• Eligible patients must have adequate physical function to tolerate the chemotherapy conditioning regimen and the HSCT, as measure by:

  1. Renal: creatinine clearance or GFR ≥50 ml/min/1.73m2, and not requiring dialysis
  2. Pulmonary: Because patients with SCID frequently present with infectious pneumonia causing ventilatory failure, patients will be considered for enrollment in the study even if respiratory failure requiring mechanical ventilatory support is present. In patients recently diagnosed with pneumonia, efforts to stabilize the respiratory status will be made prior to enrollment in the study.
  3. Infectious disease status. The presence of infection per se will not be a reason for exclusion from the study. Patients with SCID are frequently infected with both routine pathogens as well as opportunistic infections. Antibiotic, antifungal and antiviral prophylaxis and therapy will be instituted as clinically indicated. Despite the use of antimicrobial therapy, the ability to control infections will not be achieved unless HSCT is performed. Therefore, subjects may be enrolled in the study, even though infection is present, because control of infection may depend on engraftment of a donor immune system.
  4. Patients will be 0-21 years of age.

Exclusion Criteria:

• Patient with histocompatible sibling or other related donor
• End-organ failure that precludes the ability to tolerate the transplant procedure, including conditioning.
• Renal failure requiring dialysis
• Congenital heart disease resulting in congestive heart failure
• Severe CNS disease, e.g., coma or intractable seizures
• Ventilatory failure due to non-infectious etiology
• Major congenital anomalies that adversely affect survival, eg CNS malformations
• Metabolic diseases that would affect transplant survival, eg urea cycle disorders
• HIV infection

Since the only chance of survival for patients with SCID is successful transplantation, all patients with SCID will be considered to be potential subjects for the study, regardless of end-organ dysfunction.