Gene therapy offers hope for 'Bubble Boy' disease, but leukemia risk remains

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Diagnosis of SCID-X1 based on immunophenotype (\<200 CD3+ autologous T cells, and confirmed by DNA sequencing) AND 2. Lack an HLA identical (A, B, C, DR, DQ) related donor AND either one of the following: 1\. Patients in good clinical condition who do not have a readily available HLA identical (A,B,C,DR,DQ) unrelated donor (readily available defined as: a donor confirmed within 6 weeks of searching, with ability to transplant within 3 months of diagnosis). 2\. Patients with an active, therapy-resistant infection or other medical conditions that significantly increase the risk of allogeneic transplant. Examples of "therapy-resistant infections that significantly increase the risk of allogeneic transplant" include but are not limited to: 1. interstitial pneumonia due to adenovirus or parainfluenzae virus. 2. protracted diarrhea requiring total parenteral nutrition. 3. disseminated BCG infection. 4. virus-induced lymphoproliferative disease. 5. any active opportunistic infection (eg, due to Pneumocystis jiroveci, cytomegalovirus,cryptosporidium) that does not improve on medical management. 6. active and progressive pulmonary disease requiring mechanic ventilation. Inclusion of patients with disease-related organ dysfunction is justified by the known poor outcome with standard treatment and the potential life-saving nature of the treatment proposed. Patients who are on high-dose steroids or other immunosuppressive agents will also be considered eligible, because use of these drugs is common in patients with SCID and maternal T cell engraftment or who present with severe interstitial lung disease. Use of immunosuppressive drugs does not affect efficacy of hematopoietic cell transplantation, and therefore should not affect efficacy of gene transfer. Exclusion Criteria: 1. No available molecular diagnosis confirming SCID-X1. 2. Patients who have an available HLA-identical related donor. 3. Diagnosis of active malignant disease other than EBV-associated lymphoproliferative disease 4. Patients with evidence of infection with HIV-1 5. Previous gene transfer 6. Major (life-threatening) congenital anomalies. Examples of "major (life-threatening) congenital anomalies" include, but are not limited to: unrepaired cyanotic heart disease, hypoplastic lungs, anencephaly or other major CNS malformations, other severe non-repairable malformations of the gastrointestinal or genitourinary tracts that significantly impair organ function. 7. Other conditions which in the opinion of the P.I. or co-investigators, contra-indicate collection and/or infusion of transduced cells or indicate patient's inability to follow the protocol. These may include for example clinical ineligibility to receive anesthesia, severe deterioration of clinical condition of the patient after collection of bone marrow but before infusion of transduced cells, or documented refusal or inability of the family to return for scheduled visits. There may be other unforeseen rare circumstances that would result in exclusion of the patient, such as sudden loss of legal guardianship. Although the presentation of the disease may be variable in type, the severity of the immunodeficiency is uniform. The gene transfer protocol will be instituted in the place of haploidentical transplant for those patients who do not have a matched family donor or in whom an unrelated donor transplant is not indicated for the reasons specified above. Apart from the gene transfer protocol, the patients will not undergo additional procedures that would not form part of an equivalent haploidentical transplantation regimen, and will not receive conditioning chemotherapy.