Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) Registry for Patients Treated With Strimvelis (Previously GSK2696273) Gene Therapy: Long-Term Prospective, Non-Interventional Follow-up of Safety and Effectiveness

Overall survival

时间窗: After 15 years of follow-up, it will continue to be solicited every 2 years until the registry closes

Number and causes of death and time of onset of fatal events will be summarized. Starting time will be the date of therapy administration.

Absolute cluster of differentiation (CD)3+ T-cell for Immune reconstitution assessment

时间窗: Up to 15 years

CD3+ T-cell counts will be assessed

Number of subjects with the use of medications/treatments of interest

时间窗: Up to 15 years

Subjects requiring ERT, HSCT, radiotherapy or cytotoxic agents will be assessed

Growth percentile in body weight

时间窗: Up to 15 years

Subject's weight will be superimposed against gender specific WHO standard growth charts

Percentage of subjects with severe infections

时间窗: Up to 15 years

Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization

Absolute CD19+ B-cell counts for Immune reconstitution assessment

时间窗: Up to 15 years

CD19+ B-cell counts will be assessed

Vector copy number measured in peripheral blood mononuclear cells (PBMCs)

时间窗: Up to 15 years

Vector copy number will be measured

Length of hospital stay

时间窗: Up to 15 years

Duration of the hospitalization will be monitored

Absolute peripheral lymphocyte for Immune reconstitution assessment

时间窗: Up to 15 years

Peripheral lymphocyte will be assessed

Intervention free survival

时间窗: Up to 15 years

Intervention is defined as hematopoietic stem cell transplantation (HSCT) or \>3 months of enzyme replacement therapy (ERT)

Phytohaemagglutinin (PHA) and anti CD-3 as a measure for T cell function

时间窗: Up to 15 years

Phytohaemagglutinin (PHA) and anti CD-3 will be assessed

Growth percentile in body height

时间窗: Up to 15 years

Subject's height will be superimposed against gender specific World Health Organization (WHO) standard growth charts

Deoxyadenosine nucleotides (dAXP) levels in red blood cells for the measurement of systemic metabolite detoxification

时间窗: Up to 15 years

Deoxyadenosine nucleotides (dAXP) levels will be assessed in red blood cells

Number of subjects with adverse events of interest

时间窗: Up to 15 years (oncogenesis will continue to be solicited every 2 years until the registry closes)

AEs and SAEs related to medical or surgical procedures associated with Strimvelis™ administration (e.g. central venous catheter, busulfan conditioning); oncogenesis, autoimmunity, unsuccessful response to gene therapy, hypersensitivity to the product, risks related to residuals present in the drug product administered to the patient, risks related to short shelf-life of product, non-immunologic manifestations of ADA-SCID (e.g. hepatic steatosis, cognitive defects, behavioural abnormalities, hearing impairment), replication competent retrovirus.

Number of subjects with fertility and pregnancy related outcomes

时间窗: After 15 years of follow-up, it will continue to be solicited every 2 years until the registry closes

Labor and delivery information, full term pregnancy, caesarean section, abortion, miscarriage, ectopic, stillbirth rates will be assessed. Both male and female fertility issues will be analyzed.

Number of subjects with severe infections

时间窗: Up to 15 years

Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization

Scores for Ages and Stages Questionnaire-3[ASQ-3]

时间窗: Up to 15 years

Where they are used routinely as part of a physician's standard of care or where permitted by local authorities as non-interventional assessments. The ASQ-3 includes a series of questions designed to assess 5 areas of development: communication, gross motor, fine motor, problem solving, and personal social. The questions target behaviours that are appropriate for particular developmental milestones.

Number of subjects with non-immunological manifestations of ADA SCID

时间窗: Up to 15 years

Subjects will be examined for hepatic steatosis, cognitive deficits, behavioural abnormalities including suspected or diagnosed attention deficit hyperactivity disorder, autism, or hearing impairment

Pediatric development and quality of life data

时间窗: Up to 15 years

Determination of attendance at school, if appropriate for age; whether the child is in an age appropriate grade/class at school; whether the child requires special educational support (example \[e.g.\] dedicated tutor); participation in sports as desired by child; requirement for hearing aid(s); adequate response to childhood vaccinations; severity of impact of a child's health on the guardian's intended employment and Karnofsky/Lansky performance status

Scores for Pediatric Quality of Life Questionnaire (Peds-QL)

时间窗: Up to 15 years

Where they are used routinely as part of a physician's standard of care or where permitted by local authorities as non-interventional assessments. The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. 4 dimensions (physical, emotional, social, \& school functioning) are scored.

Number of subjects with any adverse events (AEs) and any serious adverse events (SAEs) as a safety measure

时间窗: Up to 15 years

AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE

Number of subjects with abnormal clinical laboratory blood test results as a safety measure

时间窗: Up to 15 years

Biochemistry, hematology and TSH parameters were assessed

Data from Retroviral Insertion Site (RIS) analysis and replication competent retrovirus (RCR)

时间窗: Up to 15 years

RIS and RCR will be performed when suspected malignancy or after a diagnosis of malignancy