Wiskott - Aldrich syndrome (WAS) is a rare serious medical condition that causes problems both with the immune system and with easy bruising and bleeding. The immune abnormalities cause patients with WAS to be very susceptible to infections. Depending on the specific type of primary immune deficiency diseases, there are effective treatments, including antibiotics, cellular therapy and gene therapy, but studies of large numbers of patients are needed to determine the full range of causes, natural history, or the best methods of treatment for long term success. This multicenter study combines retrospective, prospective and cross-sectional analyses of the transplant experiences for patients with WAS who have already received HCT since 1990, or who will undergo Hematopoietic cell transplant (HCT) during the study period. The retrospective and prospective portions of the study will address the impact of a number of pre and post-transplant factors on post-transplant disease correction and ultimate benefit from HCT and the cross-sectional portion of the study will assess the benefit of HCT 2 years post-HCT in consenting surviving patients.
Study Type
OBSERVATIONAL
Enrollment
305
Department of Pediatrics, University of Alabama at Birmingham
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California
Los Angeles, California, United States
Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles,
Los Angeles, California, United States
Lucile Salter Packard Children's Hospital at Stanford
Palo Alto, California, United States
Longitudinal Analysis: Overall Survival From Time of HCT/Gene Therapy
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.
Time frame: an expected average of 5 years
Cross-Sectional Analysis: Proportion of Participants Achieving Full T Cell Reconstitution
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
Time frame: an expected average of 5 years
Cross-Sectional Analysis: Proportion of Participants Achieving Full B Cell Reconstitution
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
Time frame: an expected average of 5 years
Cross-Sectional Analysis: Proportion of Participants Achieving Resolution of thrombocytopenia
Resolution of thrombocytopenia defined by Platelets ≥ 150,000/microliter (transfusion independent for at least 7 consecutive days)
Time frame: an expected average of 5 years
Cross-Sectional Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL
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
Time frame: an expected average of 5 years
Cross-sectional Analysis: Day of Recovery of Platelet Count to 20,000 / uL
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.
Time frame: an expected average of 5 years
Cross-sectional Analysis: Day of Recovery of Platelet Count to 50,000 / uL
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.
Time frame: an expected average of 5 years
Longitudinal Analysis: Proportion of Participants Achieving Hematologic Reconstitution
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
Time frame: an expected average of 5 years
Longitudinal Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL
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.
Time frame: an expected average of 5 years
Longitudinal Analysis: Day of Recovery of Platelet Count to 20,000 / uL
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.
Time frame: an expected average of 5 years
Longitudinal Analysis: Day of Recovery of Platelet Count to 50,000 / uL
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.
Time frame: an expected average of 5 years
Longitudinal Analysis: Proportion of Participants Achieving Full T Cell Immune Reconstitution
* 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.
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University of California, San Francisco Benioff Children's Hospital
San Francisco, California, United States
Children's Hospital Denver, University of Colorado
Denver, Colorado, United States
Nemours Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Hospital-George Washington University School of Medicine and Health Sciences
Washington D.C., District of Columbia, United States
Blood and Marrow Transplant Program, Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
...and 33 more locations
Time frame: an expected average of 5 years
Longitudinal Analysis: Proportion of Participants Achieving Full B Cell Immune Reconstitution
* 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.
Time frame: an expected average of 5 years
Longitudinal Analysis: State of Lineage Specific Chimerism (HCT Stratum)
Peripheral blood chimerism will be assessed by FISH XX/XY, STRs, or WASP expression.
Time frame: an expected average of 5 years
Longitudinal Analysis: Definition of Graft Failure / Rejection
* 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.
Time frame: an expected average of 5 years
Longitudinal Analysis: Severe bleeding episodes
Any severe bleeding episode requiring platelet and/or RBC transfusion(s)
Time frame: an expected average of 5 years
Longitudinal Analysis: Malignancy
New onset or relapse of lymphoid malignancy confirmed by relevant pathologic and genetic features.
Time frame: an expected average of 5 years
Longitudinal Analysis: Growth
Z score of weight and height pre-HCT/gene therapy and post-HCT/gene therapy.
Time frame: an expected average of 5 years
Longitudinal Analysis: Incidence of Acute GVHD
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.
Time frame: an expected average of 5 years
Longitudinal Analysis: Incidence of Chronic GVHD
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.
Time frame: an expected average of 5 years
Longitudinal Analysis: Autoimmunity disorders
Incidence of documented autoimmunity disorders
Time frame: an expected average of 5 years
Longitudinal Analysis: Infections / blood borne infections
1. 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. 2. 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. 3. 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. 4. New episodes of infections due to meningococcus, pneumococcus or hemophilus. 5. Lymphoproliferative disease due to EBV.
Time frame: an expected average of 5 years
Cross-sectional Analysis: Current State of Lineage Specific Chimerism (HCT Stratum)
Peripheral blood donor chimerism will be assessed by FISH XX/XY, STR, and/or WASP expression
Time frame: an expected average of 5 years
Cross-sectional Analysis: Current frequency and severity of infections
Time frame: an expected average of 5 years
Cross-sectional Analysis: Current Status of Growth
Current Z score of weight and height pre-HCT/gene therapy and post-HCT/gene therapy.
Time frame: an expected average of 5 years
Cross-Sectional Analysis: Graft-versus-host Disease (GvHD)
Presence of chronic GVHD, current assessment; graded as limited or extensive
Time frame: an expected average of 5 years
Cross-Sectional Analysis: Autoimmunity Disorders
Presence of autoimmunity disorders
Time frame: an expected average of 5 years
Cross-sectional Analysis: Severe Bleeding Episodes
Any severe bleeding episode requiring platelet and/or RBC transfusion(s) during the previous year.
Time frame: an expected average of 5 years
Cross-sectional Analysis: fertility
Whether the subject has biological offspring will be recorded.
Time frame: an expected average of 5 years
Cross-sectional Analysis: malignancy
New onset or relapse of lymphoid malignancy confirmed by relevant pathologic and genetic features.
Time frame: an expected average of 5 years
Cross-sectional Analysis: Quality of Life Questionnaire
Age appropriate testing will be performed at the cross-sectional visit inpatients surviving at least two years post-transplant
Time frame: an expected average of 5 years