A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID Since January 1, 1968
Prospective eval of children with SCID who are treated under several protocols to determine the patient/ recipient/transplant (tx) -related variables-most important in determining outcome, pre-, post- and peri-tx data will be collected on all children enrolled. 3 strata: A) classic SCID , B) leaky SCID, Omenn syndrome and reticular dysgenesis with limited T cell diversity or number and reduced function, and C) Adenosine Deaminase-SCID (ADA deficient SCID)- Adenosine Deaminase is an enzyme deficiency X-Gene Linked SCID (XSCID)-tdenotes type of genetic defect- patients receiving alternative therapy (Polyethylene Glycol Adenosine Deaminase (PEGADA) ERT or gene therapy. PEGADA in an enzyme). Each stratum will be analyzed separately. Outcomes for Strata B and C will utilize descriptive statistics due to number of subjects.
Hypothesis: to identify variables contributing to best outcomes for HCT/GT/ERT, a life-saving therapy for children w/SCID, leaky SCID, Omenn synd and reticular dysgenesis. B/c SCID and related disorders include a spectrum of immunologic presentations, and the several approaches to tx, many questions of interest and variables are to be explored.
RETRO: Prim:Strat A:Estimate the overall survival probabilities/overall survival risk factors after HCT for SCID; patient, donor/tx factors will be evaluated for contribution to survival.
Sec:Strat A:Determine effects of donor, recipient and treatment factors after allogeneic HCT for SCID at different ages.on subjects having durable engraftment of T, B, and myeloid lineages, and the subjects having successful/sustained immunologic reconstitution, including T cell function and B cell function.
Prim:Strat B:Estimate overall survival of reticular dysgenesis Omenn[Right Quote]s Syndrome or [Double Quote]Leaky SCID[Double Quote] following allogeneic HCT and assess whether tx outcomes are influenced by patient, donor, and/or tx characteristics.
Sec:Strat B:Evaluate donor, recipient and tx factors including engraftment and quality of immune reconstitution as contributors to clinical outcome (occurrence of post-tx infections, GVHD, autoimmunity, growth and development, and quality of life).
Strat C includes patients who receive alternative therapy. Obj: evaluate alternative HCT therapies (supportive or curative outcome and immune reconstitution) and to identify factors contributing to early demise.
CROSS: Prim Obj, Strat A:Evaluate current survivors of HCT for SCID as to the effects of patient, donor and tx-related factors on the degree of immune reconstitution of T, B and NK cells.
Sec Obj, Strat A:Comprehensively evaluate current survivors of txs for SCID as to the effects of patient, donor and tx-related factors on current health.
Tert Obj, Strat A:Assess in a representative cadre of currently surviving and consenting patients who received HLA haplotype disparate txs for SCID with full reconstitution of T, B and NK cell function, or full T cell reconstitution but impaired or absent B cell and/or NK cell function..
Prim Obj, Strat B:Assess in current survivors of txs for reticular dysgenesis, Omenn syndrome or leaky SCID the influence of tx type and tx conditioning on the level of T, B and NK cell immune reconstitution.
Sec Obj, Strat B:Assess in current survivors of HCT for these SCID-related disorders the influence of SCID variant, tx type and tx conditioning on current health, as measured by Karnofsky or Lansky functional scores, frequency, type and chronicity of infections, abnormalities of growth or organ function, neurodevelopment and neurocognitive function, presence or absence of autoimmune disorders, quality of life and presence or absence or malignancy.
Prim Obj for Subjects Who Do Not Go to Tx, Strat C:Assess in current survivors the effects of chronic treatment with PEG-ADA ERT or gene therapy in patients with ADA deficient or X-linked SCID on the level of T, B and NK cell immune reconstitution achieved.
Patients eligible for the retrospective analysis include all patients diagnosed to have SCID who were treated at the institutions participating in this consortium since January 1, 1968, who are not already enrolled on PIDTC Protocol 1 before starting HCT/GT/ERT. Subjects who received hematopoietic stem cell transplantation prior to enrolling with PIDTC are eligible for the retrospective study PIDTC Protocol # 6902. The enrollment criteria for subjects who died prior to definitive therapy are the same as for Strata A, B and C.
Please refer to section 7.8.4 where criteria for donor selection and inclusion is discussed. The primary criteria for donor selection is that they are a donor of a haplodisparate graft to an enrolled PID patient/subject. The identification and recruitment of subjects, or subjects and their donors, for participation in the investigational studies may be
* non-random due to factors such as the geographic location of the subject[Single Quote]s transplant center in relation to the center where the investigational study will be performed,
* the availability of both a subject and the donor of that subject[Single Quote]s haplodisparate graft, or
* the interest of a subject to participate in a particular investigational study.