Trial Search Results

Natural History Study of SCID Disorders

Individuals with Primary Immune Deficiency (PID) may develop severe, life-threatening infections as a result of inherited defects in the genes that normally instruct blood-forming cells to develop and to fight infections. PID diseases include Severe Combined Immune Deficiency (SCID), leaky SCID, Omenn syndrome (OS), and Reticular Dysgenesis (RD). PIDs may be treated by transplantation of bone marrow stem cells from a healthy person or, in some cases, by enzyme replacement or by gene therapy. Patients with SCID were among the first to receive bone marrow stem cell (also called hematopoietic cells) transplantation (HCT) more than 40 years ago, and HCT is the standard treatment today for this group of diseases. Since PID diseases are rare, there are not enough patients at any single center to determine the full range of causes, natural history, or best methods of treatment. For this research study many PID centers across North America have organized into the Primary Immune Deficiency Treatment Consortium (PIDTC) to pool their experience and study PIDs together. The overall goal of this study is the prospective evaluation of children with SCID and related disorders who are treated under a variety of protocols at participating institutions. The study aims to identify variables contributing to the best outcomes for HCT.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator: Office of Rare Diseases (ORD)

Stanford Investigator(s):


Inclusion Criteria:

   - Stratum A, 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
(Classic SCID):

   - Absence or very low number (<300 /µL) of CD3+T cells, AND

   - No or very low (<10% of lower limit of normal) T cell function (as measured by
   response to phytohemagglutinin (HLA) 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:

Leaky SCID:

   - Maternal lymphocytes not detected;

   - AND either one or both of the following with rule-out of MHC Class I and II non-
   expression by flow cytometry (or histology):

      - <30% of lower limit of normal T cell function (as measured by response to PHA),

      - Absent or <10% of lower limit of normal proliferative responses to candida and
      tetanus toxoid antigens (post vaccination or exposure), with expression of HLA by

   - AND either one or both of the following:

      - ≥80% of CD3+ or CD4+ T cells are CD45RO+ (at ≤2 years of age), OR

      - Genetic abnormality for SCID.

   - AND does not meet criteria for Omenn Syndrome.

Omenn Syndrome:

   - Generalized skin rash;

   - Maternal lymphocytes not detected;

   --Note: If maternal engraftment was not assessed and ruled out, the patient is not
   eligible as Omenn Syndrome.

   - ≥80% of CD3+ or CD4+ T cells are CD45RO+ ( ≤ 2 years of age)

   - Absent or low (< 30% lower limit of normal) T cell proliferation to antigens

NOTE: If proliferation to antigen was not performed, but at least 4 of the following 8
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:

   - Hepatomegaly

   - Splenomegaly

   - Lymphadenopathy

   - Elevated IgE

   - Elevated absolute eosinophil count

   - *Oligoclonal T cells measured by CDR3 length or flow cytometry

   - *Proliferation to PHA is reduced < 30% of lower limit of normal or SI < 20

   - *Mutation to SCID causing gene.

Reticular Dysgenesis:

   - <300/µL number of T cells (CD3 < 300 / µL);

   - None or <10% lower limit of normal PHA proliferation;

   - Severe neutropenia (absolute neutrophil count < 200 /µL); AND

   - One or more of the following:

      - Sensori-neural deafness OR

      - Deficiency of marrow granulopoiesis on bone marrow examination OR

      - A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.

Stratum C, SCID with Non-HCT Treatments. Subjects who meet the following criteria and the
intention is to treat with PEG-ADA or gene transfer with autologous modified cells are
eligible for enrollment into Stratum C:

   - ADA Deficient SCID with intention to treat with PEG-ADA;

   - ADA Deficient SCID with intention to treat with gene transfer; or

   - X-linked SCID with intention to treat with gene transfer. Note: For subjects with
   presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy
   with PEG-ADA ERT or blood transfusion.

Exclusion Criteria:

-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 HIV infection (by PCR) or other cause of secondary immunodeficiency;

   - 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, transcobalamin deficiency.

   - The majority of subjects with deficiency defects such as nucleoside phosphorylase
   ,ZAP70, CD40 ligand , NEMO, XLP, cartilage hair hypoplasia or ataxia telangiectasia.

      - Case by case exceptions for Stratum B for subject(s) with one of these deficiency
      defects, as determined by the PID SCID Review Panel.

Ages Eligible for Study

N/A - N/A

Genders Eligible for Study


Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Matthew Porteus, MD