Patients Treated for SCID (1968-2010)

Study ID
DAIT RDCRN PIDTC-6902

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Gevel Jackson
214-456-7194
gevel.jackson@childrens.com

Principal Investigator
Victor Aquino, M.D.

Official Title

A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID (1968-2010) (RDCRN PIDTC-6902)

Brief Overview


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.

Participant Eligibility


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.

Inclusion Criteria:

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.

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