Patients Treated for Wiskott-Aldrich Syndrome (WAS) Since 1990

The event analyzed is death from any cause. The time to this event is the time from HCT/gene therapy to death or last follow-up.

Full T cell reconstitution is defined by all of the following:

• CD3 cell count within normal range for age.
• CD4 cell count within normal range for age.
• CD8 cell count within normal range for age
• Donor T cell chimerism > 95%
• Lymphocyte proliferation to PHA. Proliferative responses to PHA within the normal range (at or above the lower limit of normal).

When possible the proliferation to PHA should be calculated as a percentage of the lower limit of normal controls for that laboratory; alternatively, the lower limit of normal controls for the day may be used

Full B cell reconstitution is defined by all of the following:

• Quantitative immunoglobulins (IgG, IgM, and IgA) within normal range; each immunoglobulin level will be assessed separately.
• Serologic confirmation of post immunization tetanus titer in protective range.
• Serologic confirmation of post immunization pneumococcal titers in protective range (protective titers for > 50% of the serotypes contained in the vaccine) following immunization

Resolution of thrombocytopenia defined by Platelets ≥ 150,000/microliter (transfusion independent for at least 7 consecutive days)

Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL is defined as the first day of at least 3 different days the ANC is measured as 500 / uL or greater

Day of Recovery of Platelet Count to 20,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 20,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

Day of Recovery of Platelet Count to 50,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 50,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

Hematologic Reconstitution is defined as attainment of each of the following lab test values:

• Hemoglobin within normal range for age
• WBC count within normal range for age
• Absolute neutrophil count (ANC) within normal range for age
• Platelet count ≥ 150,000/microL and without transfusion for at least 7 consecutive days

Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL is defined as the first day of at least 3 different days the ANC is measured as 500 / uL or greater.

Day of Recovery of Platelet Count to 20,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 20,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

Day of Recovery of Platelet Count to 50,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 50,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

• Absolute CD3 T cell count within normal range for age
• Absolute CD4 T cell count within normal range for age
• Absolute CD8 T cell count within normal range for age
• Proliferative responses to PHA within the normal range (at or above the lower limit of normal).
• When possible the proliferation to PHA should be calculated as a percentage of the lower limit of normal controls for that laboratory; alternatively, the lower limit of normal controls for the day may be used.

• Quantitative immunoglobulins (IgG, IgM, and IgA) within normal range for age; each immunoglobulin level will be assessed separately.
• Serologic confirmation of post immunization tetanus titer in protective range.
• Serologic confirmation of post immunization pneumococcal titers in protective range (protective titers for > 50% of the serotypes contained in the vaccine) following immunization.
• Patients who remain on IVIG will be considered not B cell reconstituted.
• Normalization of isohemagglutinin titers.

Peripheral blood chimerism will be assessed by FISH XX/XY, STRs, or WASP expression.

• Less than 5% of donor cells in all lineages or in whole blood by 100 days post-HCT using standard PCR based or in situ hybridization techniques OR
• Second transplant by 100 days post-HCT (unless > 5% CD3 and purpose is to boost immune recovery).

Failure to achieve ≥5% donor cells in all lineages or in whole blood by 100 days post-HCT will be defined as graft failure/rejection. Patients who receive a second transplant by day 100 will be considered graft failure.

Any severe bleeding episode requiring platelet and/or RBC transfusion(s)

New onset or relapse of lymphoid malignancy confirmed by relevant pathologic and genetic features.

Z score of weight and height pre-HCT/gene therapy and post-HCT/gene therapy.

The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the Consensus criteria of Grades IIIV or grades III-IV acute GVHD1 are considered events. Death is a competing risk, and patients alive without acute GVHD will be censored at the time of last follow-up.

Chronic GVHD will be graded as limited or extensive.2 Occurrence of symptoms in any organ system that meet the criteria of chronic GVHD will be recorded. Death is a competing risk, and patients alive without chronic GVHD will be censored at time of last follow-up.

Incidence of documented autoimmunity disorders

• Clinical resolution of any pre-HCT opportunistic infections including but not limited to CMV, HSV1, adenovirus, EBV, and VZV. Approximate time to resolution (clinically well, off treatment, and/or negative culture/PCR assay) will be measured from the day of HCT.
• Incidence of documented severe (requiring hospitalization or resulting in death) and/or recurrent bacterial, viral or fungal infection post HCT. These will be reported by site of disease, organism, date of onset post HCT, and whether or not the infection resolved.
• Presence and resolution of severe warts (verruca vulgaris, flat warts) from the day of HCT. Whether the subject had complete resolution, partial resolution, persistent or recurrent warts will be recorded.
• New episodes of infections due to meningococcus, pneumococcus or hemophilus.
• Lymphoproliferative disease due to EBV.

Peripheral blood donor chimerism will be assessed by FISH XX/XY, STR, and/or WASP expression

Current Z score of weight and height pre-HCT/gene therapy and post-HCT/gene therapy.

Presence of chronic GVHD, current assessment; graded as limited or extensive

Presence of autoimmunity disorders

Any severe bleeding episode requiring platelet and/or RBC transfusion(s) during the previous year.

Whether the subject has biological offspring will be recorded.

New onset or relapse of lymphoid malignancy confirmed by relevant pathologic and genetic features.

Age appropriate testing will be performed at the cross-sectional visit inpatients surviving at least two years post-transplant