SCID Bu/Flu/ATG Study With T Cell Depletion

The study is being conducted to assess the following:

- overall survival

- event-free survival (events are defined as: death,non-engraftment/2nd transplant,
immune reconstitution failure)

- acute toxicity of the conditioning regimen

- engraftment frequency immune reconstitution frequency and tempo acute and chronic
graft-versus-host disease (GVHD), frequency and severity.

The outcome from this protocol will be compared to the retrospective cohort consisting of
all patients who have undergone haplo-identical HSCT for SCID at CHLA from 1984-2006 based
on the assessment of the above-listed endpoints.

The CliniMACS device will be used for CD34+ selection in place of the Isolex 300i. The
CliniMACS CD34 Reagent System is an investigational medical device that has not yet been
approved by the FDA. This device is used in vitro to select and enrich specific cell
populations. When using the CliniMACS CD34 Reagent, the system selects CD34+ cells from
heterogenous hematological cell populations for transplantation in cases where this is
clinically indicated. Based on the gathered data, CliniMACS has not been a contributing
factor in the toxicity of patients, although, may have a potential of eliciting "antibody"
reactions in some patients, the process has been of significant life-saving benefit as
compared to the potential risks.

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.