Autologous Gene Therapy for Artemis-Deficient SCID

Eligibility Criteria

• * ≥2.0 months of age at initiation of busulfan conditioning
• * Diagnosis of typical or leaky ART-SCID:
• * Artemis deficiency; AND
• * CD3 count \< 300 autologous cells/µL (typical ART-SCID) OR spontaneous maternal chimerism, OR CD3 count \>300/µL but with restricted T cell receptor Vb diversity, defined as 18/24 or fewer polyclonal families.
• * Declining CD3 donor chimerism with at least 3 evaluations separated by at least 1 month prior to time of enrollment OR \< 5% overall donor chimerism in blood and marrow at ≥3 months post transplant.
• * Incompletely reconstituted T cell immunity at ≥6 months (1 of the following 2):
• * CD4 \< 200/μL AND CD45 cell PHA \< 50% of the lower limit of normal for lab;
• * CD4 CD45RA \< 20% of total CD4 cells OR T cell receptor Vb diversity is restricted, defined as 18/24 or fewer polyclonal families.
• * No donor B cells OR lack of B cell function (immunoglobulin M isohemagglutinins \< 1:8 (not blood type AB) AND immunoglobulin A (IgA) or IgM values below reference range for age AND if not receiving intravenous immunoglobulin (IVIG), no protective level of antibody to tetanus immunization x2).
• * Clinical manifestations consistent with persistent T and B cell immunodeficiency e.g., chronic infection including norovirus, cytomegalovirus, human herpes virus 6; OR acute or recurrent infection (e.g., PJP), bronchiectasis, chronic sinusitis.
• * Have no prior exposure to high dose busulfan (≥10 mg/kg total dose or average cumulative exposure of ≥40 mg\*hr/L). If the total cumulative AUC including previous busulfan exposure plus the dose to be administered in this protocol is predicted to be ≤60 mg\*hr/L, then patient would be eligible providing other criteria are satisfied.
• * No medically eligible HLA-identical sibling with a normal immune system who could serve as an allogeneic bone marrow donor (applies to newly diagnosed patients only).
• * Liver function tests (aspartate aminotransferase, alanine transaminase, gamma-glutamyl transferase) \> three times the upper limit of normal for lab and/or total bilirubin \>1.50 mg/dl at the time of planned initiation of busulfan conditioning.
• * Prior history of veno-occlusive disease (Sinusoidal obstruction syndrome) of the liver.
• * Medically eligible HLA-matched sibling (applies to newly diagnosed patients only).
• * Evidence of HIV infection by polymerase chain reaction or p24 antigen testing.
• * Unable to tolerate general anesthesia and/or marrow harvest or peripheral blood stem cell collection (apheresis) or insertion of central venous catheter.
• * Presence of a medical condition indicating that survival is predicted to be less than 4 months, such as the requirement for mechanical ventilation, severe failure of a major organ system, or evidence of a serious, progressive infection that is refractory to medical therapy.
• * Pregnancy
• * A social situation indicating that the family may not be able to comply with protocol procedures and recommended medical care and follow-up.
• * Other conditions which in the opinion of the Principal Investigator and/or co-investigators, contra-indicate the infusion of transduced cells or study participation.