Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)

* INCLUSION CRITERIA: * A proven mutation in the common gamma chain gene as defined by direct sequencing of patient DNA * No available HLA matched sibling donor as determined before enrollment (HLA typing will be performed prior to enrollment) * Must be between 2 and 50 years of age and weigh 10 kg * If previously transplanted, must be 18 months post-HSCT * Expected survival of at least 120 days. * Participants of reproductive potential must agree to consistently use highly effective contraception throughout study participation and for at least 2 years post-treatment. Acceptable forms of contraception are: --For males: Condoms or other contraception with partner. * Documented to be negative for HIV infection by genome PCR * The patient must be judged by the primary evaluating physician to have a suitable family and social situation consistent with ability to comply with protocol procedures and the long-term follow-up requirements. * Medical lab data (historical) of severe B cell dysfunction (low or absent IgG levels, failed immune response to vaccines); OR demonstrated requirement for intravenous gamma globulin (IVIG) (significant drop over 3 to 6 weeks between peak and trough IgG levels). * Must be willing to have blood and tissue samples stored IN ADDITION, patients must satisfy the following Laboratory Criteria AND Clinical Criteria Laboratory Criteria: (\>=1 must be present) I. CD4+ lymphocytes: absolute number \<= 50% of the lower limit of normal (LLN) II. CD4+ CD45RA+ lymphocytes: absolute number \<= 50% of the LLN OR T-cell receptor excision circles (TRECs) \<= 5% of normal for age. III. Memory B Cells: absolute number \<= 50% of LLN IV. Serum IgM\<normal for age V. NK cells: absolute number \<= 50% of LLN VI. Lymphocyte proliferative response to each of 2 mitogens, phytohemagglutinin (PHA) and concanavalin A (ConA), is \<= 25% compared with a normal control. VII. Molecular spectratype analysis- absent or very oligoclonal (1-3 dominant peaks) in \>=6 of the 24 VBeta T-cell receptor families. Clinical Criteria: (\>=1 must be present): I. Infections (not including molluscum, warts or mucocutaneous candidiasis; see vii and viii below): Three significant new or chronic active infections during the 2 years preceding evaluation for enrollment, with each infection accounting for one criteria. Infections are defined as an objective sign of infection (fever \>38.3 degrees C \[101 degrees F\] or neutrophilia or pain/redness/swelling or radiologic/ultrasound imaging evidence or typical lesion or histology or new severe diarrhea or cough with sputum production). In addition to one or more of these signs/symptoms of possible infection, there also must be at least 1 of the following criteria as evidence of the attending physician's "intent to treat" a significant infection (a. and b.) or objective evidence for a specific pathogen causing the infection (c.) 1. Treatment (not prophylaxis) with systemic antibacterial, antifungal or antiviral antibiotics 14 days OR 2. Hospitalization of any duration for infection OR 3. Isolation of a bacteria, fungus, or virus from biopsy, skin lesion, blood, nasal washing, bronchoscopy, cerebrospinal fluid or stool likely to be an etiologic agent of infection II. Chronic pulmonary disease as defined by: 1. Bronchiectasis by x-ray computerized tomography OR 2. Pulmonary function test (PFT) evidence for restrictive or obstructive disease that is 60% of Predicted for Age OR 3. Pulse oximetry 94% in room air (if patient is too young to comply with performance of PFTs). III. Gastrointestinal enteropathy: 1. Diarrhea-watery stools 3 times per day (of at least 3 months duration that is not a result of infection as defined in criterion # i. above) OR 2. Endoscopic evidence (gross and histologic) for enteropathy (endoscopy will only be performed if medically indicated) OR 3. Other evidence of enteropathy or bacterial overgrowth syndrome: including malabsorption of fat-soluble vitamin(s), abnormal D-xylose absorption, abnormal hydrogen breath test, evidence of protein losing enteropathy (for example increasingly high or frequent dosing of intravenous gamma globulin supplement required to maintain blood IgG level). IV. Poor nutrition: Requires G-tube or intravenous feeding supplement to maintain weight or nutrition. V. Auto- or allo-immunity: Examples must include objective physical findings that include, but are not limited to any one of alopecia, severe rashes, uveitis, joint pain with redness or swelling or limitation of movement that is not a result of infection, lupus-like lesions, and granulomas (Does not include auto- or allo-immune enteropathy which is criterion iii). Where possible and appropriate, diagnosis will be supported by histopathology or other diagnostic modality. VI. Failure to grow in height: \<=3rd percentile for age VII. Skin molluscum contagiosum OR warts (this criterion is satisfied if molluscum consists of 10 lesions or there are two or more lesions at each of two or more widely separated anatomic sites; or there are 3 warts at different anatomic sites at the same time; or the patient has both molluscum and warts) VIII. Mucocutaneous candidiasis (chronic oral thrush or candida esophagitis or candida intertriginous infection or candida nail infections; must be culture positive to satisfy this criterion) IX. Hypogammaglobulinemia: requires regular IgG supplementation Criteria for eligibility for Campath (alemtuzumab): Evidence of organ disease attributable to T cell dysregulation, for example, elevated transaminases. EXCLUSION CRITERIA: * Any current or pre-existing hematologic malignancy * Documented HIV-1 infection * Documented active Hepatitis B infection * Childhood malignancy (occurring before 18 years of age) in the patient or a first degree relative, or previously diagnosed known genotype of the subject conferring a predisposition to cancer (no DNA or other testing for cancer predisposition g