Patients Treated for SCID (1968-2010)
- at San Francisco, California and other locations
- study startedestimated completion:
- Principal Investigator
- Morton J Cowan
People 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. Researchers will collect information on your general health, psychological and developmental health, and the current status of your immune system to help better define future approaches to PID treatments.
A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID (1968-2010) (RDCRN PIDTC-6902)
SCID ADA-SCID XSCID Leaky SCID Omenn Syndrome Reticular Dysgenesis
Investigators from institutions participating in this consortium will submit data to the PIDTC Review Panel to determine eligibility and stratum assignment. The eligibility of the patients and their stratification by SCID variant and treatment employed for SCID will be as follows.
Strata A, B, and C (Part 1 - Retrospective Study).
Patients eligible for the retrospective analysis include all patients diagnosed to have SCID who were treated at the institutions participating in this consortium from 1968 until December 31, 2010, who are not already enrolled on PIDTC Protocol 1. Subjects who received HCT/GT/ERT prior to December 31, 2010 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. Patients who meet the following inclusion criteria and who received HCT are eligible for enrollment into Stratum A (Classic 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, but with < 10% of normal T cell function (as measured by response to PHA).
Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis. Patients who meet the following criteria are eligible for enrollment into Stratum B of the study: Leaky SCID
Reduced number of CD3 T cells - for age up to 2 years ≥ 300 and < 1000/microliter; for
2 years up to 4 years ≥ 300 and < 800/microliter ; for> 4 years ≥ 300 and <600/microliter
Absence of maternal engraftment ≥ 10% and ≤ 30% of lower limit of normal T cell function (as measured by response to PHA)
Omenn Syndrome (OS)
- Generalized skin rash
- Absence of maternal engraftment
- Detectable CD3 T cells, ≥ 300/microliter
- 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 9 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 <30% of lower limit of normal or SI <20; *Proliferative response in mixed leukocyte reaction is reduced <30% of lower limit of normal or Stimulation Index (SI)<5
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)
Sensorineural deafness and/or absence of granulopoiesis at bone marrow examination
Stratum C, SCID with Non-HCT Treatments. Patients 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.
- ADA Deficient SCID treated with PEG-ADA
Any SCID treated with 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.
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
- University of California San Francisco Children's Hospital accepting new patients
San Francisco, California, 94143-1278, United States
- Stanford University accepting new patients
Stanford, California, 94305, United States
- Children's Hospital Los Angeles accepting new patients
Los Angeles, California, 90027, United States
- University of California, Los Angeles accepting new patients
Los Angeles, California, 90095-1752, United States
- accepting new patients
- Start Date
- Completion Date
- National Institute of Allergy and Infectious Diseases (NIAID)
- The Rare Diseases Clinical Research Network (RDCRN)
- Primary Immune Deficiency Treatment Consortium (PIDTC)
- Lead Scientist
- Morton J Cowan
- Study Type
- Last Updated
- September 12, 2016
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