Ensayos clínicos

Inclusion Criteria

• Stratum A
  • Classic Severe Combined Immunodeficiency patients
  • Intention to treat with allogeneic hematopoietic cell transplant (HCT)
  • Absence or very low number (< 300 / ul) of T cells, AND no or very low (<10% of lower limit of normal) T cell function (as measured by response to phytohemagglutinin OR T cells of maternal origin present, but with <10% of lower limit of normal T cell function (as measured by response to PHA)
• Stratum B
  • Leaky SCID, Omenn Syndrome, Reticular Dysgenesis Patients 
  • Intention to treat with HCT 
• For leaky SCID
  • <1000 / ul T cell number at < age 2 years
  • < 800 / ul T cell number at age 2 through < 4 years
  • < 600 / ul at > 4 years and maternal lymphocytes not detected
  • AND either one or both of the following with rule-out of MHC Class I or II non-expression by flow cytometry (or histology)
    • ≥ 10% and ≤ 30% of lower limit of normal T cell function (as measured by response to PHA)
    • Absent proliferative responses to candida and tetanus toxoid antigens (post vaccination or exposure), with expression of HLA by flow/serology
• For Omenn Syndrome
  • Generalized skin rash
  • Maternal lymphocytes not detected
  • Absent or low (< 30% lower limit of normal) T cell proliferation to antigens
  • > 80% of CD4 T cells are CD45RO+ (< 2 years of age)
• For Reticular Dysgenesis
  • < 300 / ul T cell number
  • None or < 10% lower limit of normal PHA proliferation
  • Sensori-neural deafness
  • Severe neutropenia (< 200 / uL and unresponsive to G-CSF) and deficiency of marrow granulopoiesis unless there is known adenylate kinase 2 (AK2) pathogenic mutation(s) identified
• Stratum C
  • SCID with Non-HCT Treatment Patients 
  • Intention to treat with PEG-ADA or gene transfer with autologous modified cells
  • ADA Deficient SCID with intention to treat with PEG-ADA
  • ADA Deficient SCID with intention to treat with gene transfer
  • X-linked SCID with intention to treat with gene transfer

Exclusion Criteria

• Presence of an HIV infection (by PCR) or other cause of secondary immunodeficiency
• Presence of DiGeorge syndrome
• Most patients with other PIDs such as nucleoside phosphorylase deficiency, ZAP70 deficiency, CD40 ligand deficiency, NEMO deficiency, XLP, cartilage hair hypoplasia or ataxia telangiectasia will not meet the inclusion criteria for Stratum A, B, or C above
  • However, a patient with one of the above may meet the inclusion criteria for Stratum B and if so will be included
• MHC Class I and MHC Class II antigen deficiency are specifically excluded
• Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency, transcobalamin deficiency