Patients Treated for SCID (1968-Present)


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Trial ID: NCT01346150


Individuals with a past diagnosis of severe combined immune deficiency (including many cases of "leaky SCID", Omenn syndrome, and reticular dysgenesis) who have undergone blood and marrow transplant, gene therapy, or enzyme replacement in the past may be eligible for this study. The purpose of study is to look backwards at what has already been done in the. Over 800 patients with SCID are expected to be enrolled, making this one of the largest studies ever to describe outcomes for patients with SCID treated at many different hospitals around North America.

Official Title

A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID Since January 1,1968 (RDCRN PIDTC-6902)


Inclusion Criteria:

Strata A, B, and C (Part 1 - Retrospective Study)-

   - Individuals with Severe Combined Immune Deficiency (SCID) diagnosis who:

   --were treated at a location participating in this consortium from 1968 until present,

   --are not enrolled in RDCRN PIDTC-6901 ( ID: NCT01186913).

   - Subjects who received HCT/GT/ERT prior to the present date are eligible for the
   retrospective study. The enrollment criteria for subjects who died prior to definitive
   therapy are the same as for Strata A, B and C.

Stratum A, Typical SCID:

   - Individuals who meet the following inclusion criteria and who received HCT are
   eligible for enrollment into Stratum A of the study:

      - 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 cells of maternal origin present.

      - If maternal cells are present but the patient does not meet criteria for very low
      T cell function as defined, the assigned reviewers for the potential subject, and
      if necessary, the full PID-SCID RP will review the laboratory report to determine
      if criteria of maternal engraftment are met for Protocol 6902.

      - Laboratory report of testing for maternal engraftment is required, for evaluation
      by the PID-SCID RP.

Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis:

Individuals who meet the following criteria are eligible for enrollment into Stratum B of
the study:

Leaky SCID-

   - 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 <
   50% of lower limit of normal T cell function as measured by response to CD3/CD28
   antibody, b) Absent or < 30% lower limit of normal proliferative responses to candida
   and tetanus toxoid antigens postvaccination or exposure,

   - AND at least one of the following (a through e):

      1. Reduced number of CD3 T cells,

      2. > 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 < 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 at least one
   hypomorphic mutation in an autosomal SCID-causing gene.

   d) Low 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,

      - AND does not have known selective loss of lymphocytes, Ataxia- Telangiectasia, or
      congenital heart defect associated with lymphopenia, unless a SCID genotype is
      also present.

Omenn Syndrome (OS):

   - Generalized skin rash,

   - Maternal engraftment tested for and not detected,

   - Absent or low (up to 30% of normal) T cell proliferation to antigens to which the
   patient has been exposed.

   - If the proliferation to antigen was not performed, but at least 4 of the following 10
   supportive criteria, at least one of which must be among those marked with an asterisk
   (*) are present, the patient is eligible: hepatomegaly; splenomegaly; lymphadenopathy;
   elevated IgE; elevated absolute eosinophil count; *oligoclonal T cells measured by
   CDR3 length or flow cytometry >80% of CD4+ T cells are CD45RO+ ;*proliferation to PHA
   is reduced <50% of lower limit of normal or SI <30; *proliferative response in mixed
   leukocyte reaction is reduced to increment cpm < 20% or SI <20; hypomorphic mutation
   to SCID causing gene; low TRECs and/or percentage of CD 4+/ RA+/CD31+; or
   CD4+/RA+/CD62L+ cells below the lower limit of normal.

Reticular Dysgenesis (RD):

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

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

   - Severe congenital neutropenia (absolute neutrophil count <200/microliter),

   - AND at least one of the following:

      - Sensorineural deafness and/or absence of granulopoiesis at bone marrow
      examination and/or a deleterious AK2 mutation,

      - absence of granulopoiesis on bone marrow examination; a pathogenic mutation in
      the adenylate kinase 2 (AK2) gene identified.

Stratum C, SCID with Non-HCT Treatments:

-Individuals who meet the following criteria and were treated with PEG-ADA or gene therapy
with autologous modified cells are eligible for enrollment into Stratum C (SCID with
non-HCT treatments) of the study-

- Any SCID patient previously treated with a thymus transplant (includes intention to treat
with HCT, as well as PEG-ADA ERT or gene therapy).

Strata A, B, and C (Part 2 - Cross-Sectional Study):

Patient inclusion criteria for the cross sectional study: Eligibility for Strata A, B and C
are the same as for the retrospective study except that all the patients in the
cross-sectional study are currently surviving and are at least 2 years post the most recent
class of therapy.

Exclusion Criteria:

Parts 1 and 2 - Retrospective and Cross-Sectional Studies -

   - Lack of appropriate testing to rule out HIV infection after 1997 (p24 antigen or more
   sensitive) 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 excluded,

      - Metabolic conditions that imitate SCID or related disorders such as folate
      transporter deficiency, severe zinc deficiency, transcobalamin deficiency.


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Contact Information

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