RDCRN PIDTC Protocol # 6904

Principal Investigator: Karin Chen
Keywords: Wiskott-Aldrich Syndrome Department: Pediatric Administration
IRB Number: 00069898 Co Investigator:  
Specialty: Pediatric Hematology and Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Diana Hernandez

Brief Summary

The goals of this study will be to determine the immunologic and clinical consequences of HCT in patients with WAS. We will examine outcomes of HCT for WAS. We will analyze the importance of disease related pre transplant complications on transplant outcome and analyze which pre-transplant conditioning regimens provide the best results for these patients. We will also collect data on patients receiving gene therapy for WAS although due to the small number of subjects, analysis will be descriptive.


Study Objectives for Stratum A of the Retrospective and Prospective Cohorts of the Longitudinal

Analysis (Part 1)

The primary objectives of this study are to estimate survival at 6 months and 1, 2, 3, 5, 10, and 15 years post-HCT, 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.

These are described in detail in Section 10.2.5 “Prognostic Factors of Interest”.


Secondary objectives of the study are to determine the effects of donor, recipient and treatment related factors on the proportion of subjects having durable engraftment of T, B and myeloid lineages, and the proportion of subjects having successful immunologic and hematologic reconstitution, including T cell function, B cell function, and platelet numbers at 100 days, 6 months and 1, 2, 3-5, 6-10, 11-15, and > 15 years after HCT for WAS. Additionally, we will evaluate donor, recipient and transplant factors as well as engraftment and quality of immune reconstitution as contributors to clinical outcome, including occurrence of post-transplant infections, bleeding episodes, and/or new malignancies, GVHD, autoimmunity, growth and development, and quality of life.

We will assess the correlation of potential biomarkers such as B cell subsets, lineage specific WASP expression, extent of lineage specific donor chimerism, BCR (and/or TCR) repertoire, KREC levels, BAFF and APRIL levels, and antibody microarray studies on autoimmunity; and impact on the ultimate outcomes of HCT including prognosis with respect to survival, and immune and hematologic reconstitution.


Study Objectives for Stratum A of the Cross-Sectional Analysis (Part 2)

The primary objective of this cross-sectional study is to evaluate current survivors of HCT for WAS as to the effects of patient, donor and transplant-related factors on the degree of immune reconstitution of T, Band NK cells, and normalization of peripheral blood platelet counts.

The secondary objectives of this cross-sectional study are to comprehensively evaluate current survivors of HCT for WAS as to the effects of patient, donor and transplant-related factors on current health, as measured by Karnofsky or Lansky functional scores, frequency, type and chronicity of infections, abnormalities of growth or organ function, presence or absence of graft-versus-host disease, presence or absence of autoimmune disorders, presence or absence of severe bleeding episodes, quality of life, fertility, presence or absence or malignancy, hematological and immune reconstitution.

The extent of T, B, NK and myeloid chimerism as well as immune reconstitution will be correlated with clinical status post HCT and in particular with the persistence or resolution of autoimmunity, infections, thrombocytopenia and bleeding episodes. Potential alterations in BCR or TCR repertoire as compared to age matched controls will be correlated with the presence or absence of autoimmunity.


Study Objectives for Stratum B, Longitudinal (Part 1) and Cross-Sectional (Part 2) Analyses

Stratum B will include patients who receive alternative therapy; i.e., those who are treated using gene therapy (GT). This will represent a very small group of patients and only descriptive statistics will be available. The objective in studying this group of patients will be to evaluate alternative therapies to HCT that are potentially curative in terms of survival, outcome and immune reconstitution. For Stratum B, endpoints and outcomes for GT will be analyzed similarly to HCT where applicable. Patients in Stratum B will be evaluated from the time that therapy begins with infusion of transduced cells.

Inclusion Criteria

Participant Inclusion Criteria for Strata A and B of the Longitudinal

Analysis (Retrospective and Prospective) (Part 1)

Stratum A. WAS who have or will Receive HCT

WAS patients will be defined as males who have received an HCT since January 1, 1990 AND have:

1. thrombocytopenia (< 100K) AND EITHER

  • molecular diagnosis of WAS (raw data to be uploaded); OR


  • reduced WASP expression (raw data to be uploaded);


2. thrombocytopenia (< 100K) AND positive family history consistent with WAS diagnosis;


  1. chronic thrombocytopenia (< 100K for minimum of 3 months) AND

low mean platelet volume (MPV below normal range for age) AND EITHER


  • recurrent and/or severe infections requiring treatment and/or eczema; OR


  • lack of antibody response to polysaccharide antigens or low IgM.


*Additional laboratory abnormalities that may be supportive include: high IgA, high IgE, abnormal proliferative response to antigens (tetanus and/or candida), alloantigens (MLR), or anti-CD3.


*The PID-WAS Review Panel (see Section 4.6) may evaluate other factors for patients who do not meet the above criteria.


Genetic sequencing will be performed to confirm the diagnosis in those patients who have not been genotyped where an appropriate sample is available, but this will not be required for inclusion.


Stratum B. WAS who have or will Receive Gene Transfer

Patients who meet the above criteria and the intention is to treat with gene transfer with autologous modified cells are eligible for enrollment into Stratum B.


Participant Inclusion Criteria for Strata A and B of the Cross-Sectional Analysis (Part 2)


Inclusion criteria for the Cross-Sectional Analysis (Part 2) are identical to those listed above for the Longitudinal Analysis (Part 1). However, to be eligible for the cross-sectional study, patients must be surviving and at least 2 years after the most recent HCT or gene therapy.

Exclusion Criteria

As this is a natural history study, for both the Longitudinal Analysis (Part 1) and the Cross-Sectional Analysis (Part 2) we will not exclude any patients due to race or age who fit the inclusion criteria.