A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children with SCID Disorders

Study ID
STU 102010-169

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Children's Medical Center-Dallas

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

Principal Investigator
Victor Aquino

Summary

In this prospective natural history study, we aim to identify variables contributing to best outcomes for hematopoietic cell transplantation (HCT), which is lifesaving therapy for children with SCID, leaky SCID, Omenn syndrome and reticular dysgenesis. Because SCID and related disorders include a spectrum of immunologic presentations, and there have been several approaches to transplant, there are many questions of interest and variables to be explored.The primary objectives of this study are to estimate the 6 month and 2 year overall survival probabilities for subjects after HCT for SCID, and to study risk factors for overall survival in this patient population. A variety of patient, donor and transplant factors will be evaluated for their contribution to the outcomes described above. Secondary objectives of this study are to determine the effects of donor, recipient and treatment factors on the proportion of subjects having durable engraftment within each blood lineage, and the proportion of subjects having successful/sustained immunologic reconstitution, including T cell function and B cell function, after allogeneic HCT for SCID. Additionally, we will evaluate donor, recipient and transplant factors as well as engraftment and quality of immune reconstitution as contributors to clinical outcome; for example, occurrence of post-transplant infections, GVHD, autoimmunity, growth and development, and quality of life. We will assess findings concerning clinical history and presentation and potential biomarkers of ultimate outcome and prognosis with respect to survival and immune reconstitution.

Participant Eligibility

After patients with SCID spectrum disorders have undergone diagnostic workup per local center practice, they will be proposed for enrollment in this natural history study by investigators at participating institutions; after consent is obtained data that was collected during the diagnostic workup will be submitted for review to determine eligibility and stratum assignment.

Participant Inclusion Criteria for Strata A, B, and C
-Stratum A, Classic SCID. Patients 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) of the study:
-Absence or very low number (< 300 / ul) of T cells, AND no or very
low (<10% of lower limit of normal) T cell function (as measured by
response to phytohemagglutinin (PHA),

-T cells of maternal origin present, but with <10% of lower limit 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 and the intention is to treat with HCT are eligible
for enrollment into Stratum B (Omenn/Leaky SCID/Reticular Dysgenesis) of the
study:
- Leaky SCID
- <1000 / ul T cell number at < age 2 years; < 800 / ul T cell number at
age 2 through < 4 years; < 600 / ul at > 4 years maternal
lymphocytes not detected, AND either one or both of the following with rule-out of MHC Class I or
II non-expression by flow cytometry (or histology):
a) = 10% and = 30% of lower limit of normal T cell function (as
measured by response to PHA),

b) Absent proliferative responses to candida and tetanus toxoid antigens
(post vaccination or exposure), with expression of HLA by
flow/serology

Omenn Syndrome (OS)
- Generalized skin rash
- Maternal lymphocytes not detected
- Absent or low (< 30% lower limit of normal) T cell proliferation to antigens
> 80% of CD4 T cells are CD45RO+ (< 2 years of age)

- Reticular Dysgenesis (RD)
< 300 / ul T cell number
- None or < 10% lower limit of normal PHA proliferation
-Sensori-neural deafness
- Severe neutropenia (< 200 / uL and unresponsive to G-CSF) and deficiency of marrow granulopoiesis unless there is known adenylate
kinase 2 (AK2) pathogenic mutation(s) identified

- Stratum C, SCID with Non-HCT Treatments. Patients 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
- X-linked SCID with intention to treat with gene transfer