Trial Search Results
Natural History Study of SCID Disorders
This study is a prospective evaluation of children with Severe Combined Immune Deficiency (SCID) who are treated under a variety of protocols used by participating institutions. In order to determine the patient, recipient and transplant-related variables that are most important in determining outcome, study investigators will uniformly collect pre-, post- and peri-transplant (or other treatment) information on all children enrolled into this study.
Children will be divided into three strata:
- Stratum A: Typical SCID with virtual absence of autologous T cells and poor T cell function
- Stratum B: Atypical SCID (leaky SCID, Omenn syndrome and reticular dysgenesis with limited T cell diversity or number and reduced function), and
- Stratum C: ADA deficient SCID and XSCID patients receiving alternative therapy including PEG-ADA ERT or gene therapy.
Each Group/Cohort Stratum will be analyzed separately.
Stanford is currently accepting patients for this trial.
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator: Primary Immune Deficiency Treatment Consortium (PIDTC)
Stratum A: Typical SCID (formerly referred to as Classic SCID)- -Subjects who meet the
following inclusion criteria and the intention is to treat with allogeneic hematopoietic
cell transplant (HCT) are eligible for enrollment into Stratum A (Typical SCID) of the
- Absence or very low number of T cells (CD3 T cells <300/microliter) AND
- No or very low T cell function (<10% of lower limit of normal) as measured by response
to phytohemagglutinin (PHA) OR
- T cells of maternal origin present.
Stratum B: Leaky SCID, Omenn Syndrome, Reticular Dysgenesis-
-Subjects who meet the following criteria and the intention is to treat with HCT are
eligible for enrollment into Stratum B:
- Maternal lymphocytes tested for and not detected AND
- Either one or both of the following (a,b) :
- a.) <50% of lower limit of normal T cell function as measured by response to PHA,
OR response to anti-CD3/CD28 antibody
- b.) Absent or <30% of lower limit of normal proliferative responses to candida
and tetanus toxoid antigens
- AND at least two of the following (a through e):
- a.) Reduced number of CD3 T cells
- age ≤2 years: <1500/microliter
- age >2 years and ≤4 years: <800/microliter
- age >4 years: <600/microliter
- b.) ≥80% of CD3+ or CD4+ T cells that are CD45RO+
- AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative
- AND/OR >50% of CD3+ or CD4+T cells express HLA-DR (at <4 years of age)
- AND/OR are oligoclonal T cells
- c.) Hypomorphic mutation in IL2RG in a male, or homozygous hypomorphic mutation
or compound heterozygosity with ≥1 hypomorphic mutation in an autosomal
- d.) Low T Cell Receptor Excision Circles (TRECs) and/or the percentage of
CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal.
- e.) Functional testing in vitro supporting impaired, but not absent, activity of
the mutant protein, AND
- Does not meet criteria for Omenn Syndrome.
- Generalized skin rash
- Maternal lymphocytes tested for and not detected;
--Note: If maternal engraftment was not assessed and ruled out, the subject is not
eligible as Omenn Syndrome.
- ≥80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR
- 80% of CD3+ or CD4+T cells are CD62L negative AND/OR
- 50% of CD3+ or CD4+ T cells express HLA-DR (at <2 years of age);
- Absent or low (< 30% lower limit of normal) T cell proliferation response to antigens
(Candida, tetanus) to which the subject has been exposed
NOTE: If proliferation to antigen was not performed, but at least 4 of the following 9
supportive criteria, at least one of which must be among those marked with an asterisk (*)
below are present, the subject is eligible as Omenn Syndrome:
- Elevated IgE
- Elevated absolute eosinophil count
- *Oligoclonal T cells measured by CDR3 length or flow cytometry
- *Proliferation to PHA is reduced <50% of lower limit of normal or SI <30
- *Hypomorphic mutation in a SCID causing gene
- Low TRECS and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is
below the lower limit of normal.
- Absence or very low number of T cells (CD3 <300/µL
- No or very low (<10% lower limit of normal) T cell response to PHA
- Severe neutropenia (absolute neutrophil count < 200 /µL) AND
- ≥2 of the following (a,b,c):
- a.) Sensori-neural deafness
- b.) Deficiency of marrow granulopoiesis on bone marrow examination
- c.) A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.
Subjects who meet the following criteria and the intention is to treat with therapy other
than allogeneic HCT, primarily PEG-ADA ERT or gene therapy with autologous modified (gene
transduced) cells, are eligible for enrollment into
- ADA Deficient SCID with intention to treat with PEG-ADA ERT
- ADA Deficient SCID with intention to treat with gene therapy
- X-linked SCID with intention to treat with gene therapy
- Any SCID patient previously treated with a thymus transplant (includes intention to
treat with HCT, as well as PEG-ADA ERT or gene therapy)
- Any SCID patient who received therapy for SCID deemed "non-standard" or
"investigational", including in utero procedures.
-Subjects who meet any of the following exclusion criteria are disqualified from enrollment
in Strata A, B, or C of the study:
- Presence of an Human Immunodeficiency Virus (HIV) infection (by PCR) or other cause of
- Presence of DiGeorge syndrome
- MHC Class I and MHC Class II antigen deficiency, and
- Metabolic conditions that imitate SCID or related disorders such as folate transporter
deficiency, severe zinc deficiency or transcobalamin deficiency.
Ages Eligible for Study
N/A - N/A
Genders Eligible for Study