Natural History Study of SCID Disorders

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 20, 2010

Keywords

ClinConnect Summary

This study follows participants with SCID prospectively, meaning the study enrolls participants where there is a plan to receive a blood and marrow transplant, enzyme therapy, or gene therapy in the future. Participants are then followed according to a schedule set out by the study protocol after the procedure. There are no experimental therapies on this study.

The goal of this study is to learn more about: (1) outcomes from the treatment of SCID in the modern era of medicine (2) what factors lead to the best long-term outcomes, such as best donor, conditioning regimen, timing of transplan...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• 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 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
• • 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 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 SCID-causing gene
• • 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.
• 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:
• • Hepatomegaly
• • Splenomegaly
• • Lymphadenopathy
• • 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.
• Reticular Dysgenesis:
• • 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.
• Stratum C:
• • 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
• Stratum C:
• • 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.
• 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 Human Immunodeficiency Virus (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 or transcobalamin deficiency.