Matched Related and Unrelated Donor Stem Cell Transplantation for Severe Combined Immune Deficiency (SCID): Busulfan-based Conditioning With h-ATG, Radiation, and Sirolimus

Inclusion Criteria

• •Must have confirmed genetic diagnosis of SCID (gamma c or JAK3 deficiency) by identification of a mutation in the responsible genes or by demonstrating failure to detect gamma c or JAK3 in immune blood cells (as in the case of patients who have been treated but now have waning immunity).
• •Must have either evidence of waning immunity by T cell analysis, and/or sufficient complications from underlying disease to warrant undergoing transplantation as defined as meeting greater than or equal to1 of the following clinical criteria:
• •i- Infections (not including molluscum, warts, or mucocutaneous candidiasis; see vii and viii below): 3 significant new or chronic active infections during the 2 years preceding evaluation for enrollment, with each infection accounting for one criterion.
• •Infections are defined as an objective sign of infection (fever \>38.3 (Infinite)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 for greater than or equal to 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 less than or equal to 60% of predicted for age; OR
• •3. Pulse oximetry less than or equal to 94% in room air (if patient is too young to comply with performance of PFTs).
• •iii. Gastrointestinal enteropathy:
• •1. Diarrhea-watery stools greater than or equal to 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 at least one of the following: malabsorption of fat soluble vitamin(s), abnormal D-xylose absorption, abnormal hydrogen breath test, or evidence of protein-losing enteropathy (for example, increasingly high or frequent dosing of IV gamma globulin supplement required to maintain blood IgG level).
• •iv. Poor nutrition: Requires G-tube or IV feeding supplement to maintain weight or nutrition.
• •v. Auto- or allo-immunity: Objective physical findings including but are not limited to at least one of the following: 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 (not including auto- or alloimmune enteropathy, which is criterion iii). Where possible and appropriate, diagnosis will be supported by histopathology or another diagnostic modality.
• •vi. Failure to grow in height: less than or equal to 3rd percentile for age.
• •vii. Skin molluscum contagiosum OR warts (this criterion is satisfied if molluscum consists of greater than or equal to 10 lesions or there are greater than or equal to 2 lesions at each of two or more widely separated anatomic sites; or there are greater than or equal to 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 infection; must be culture positive to satisfy this criterion).
• •ix. Hypogammaglobulinemia: Requires regular IgG supplementation.
• •Aged 3-40 years, inclusive.
• •Must have a 6/6 HLA-MRD graft available, or an HLA-matched unrelated PBSC graft (10/10 or 9/10 mismatch) available, or a minimum of 4/6 HLA-matched cord blood product available (if the cord blood graft is less than 5.0x10(7) cells, a second appropriate 4/6 or greater match cord blood product must be available).
• •Mismatched MUD and Cord Blood transplants need to have Class I and II HLA antibody screen, DSA should be avoided.
• •Must be HIV negative.
• •Must be able to stay within 1 hour s travel of the NIH for the first 3 months after transplantation and have a family member or other designated companion to stay with during the post-transplant period.
• •Must provide a durable power of attorney (DPA) for health care decisions to an appropriate adult relative or guardian in accordance to NIH-200 NIH Advance Directive for Health Care and Medical Research Participation .
• •For participants of reproductive potential, must agree to consistently use highly effective contraception throughout study participation and for at least 3 months after the study.
• •Acceptable forms of contraception are:
• •a. For females:
• •i. Condoms, male or female, with or without a spermicide;
• •ii. Diaphragm or cervical cap with spermicide;
• •iii. Intrauterine device;
• •iv. Contraceptive pills or patch, Norplant, Depo-Provera, or other FDA-approved contraceptive method;
• •v. Male has previously undergone a vasectomy.
• •b. For males: Condoms or other contraception with partner.