Information regarding the outcomes of hematopoietic cell transplantation (HCT), currently the only available cure for patients with Wiskott Aldrich syndrome (WAS) and Chronic granulomatous disease (CGD), is lacking due to the relative rarity of these diseases, and the lack of a coordinated effort amongst centers to collect and compile complete data on these patients. Moreover, HCT still entails significant risk of both morbidity and mortality, while management of these disorders using conventional treatments continues to improve. Furthermore, continuing advances in gene therapy make it essential to identify factors that impact on transplant outcomes as well as to identify those patients who would benefit most from transplant. The Goal of Project 3 is to undertake retrospective and cross sectional studies of outcomes after HCT for WAS and CGD performed in North America in order to delineate the risks and benefits of this procedure for these two rare disorders of the immune system.
The Specific Aims are: 1) To characterize the biologic factors which determine survival, immune reconstitution and long term outcomes in WAS and 2) To determine the critical factors that predict survival and disease correction following HCT for CGD and identify those patients who should receive an HCT. Using retrospective, cross sectional and longitudinal studies we will test hypotheses concerning the degree of donor engraftment necessary to correct disease manifestations in WAS and CGD, and the type of patient with CGD most likely to benefit from HCT. The development of a consortium will allow the collection of both molecular and clinical data from a sufficient number of patients to obtain statistical significance in our analyses, which would not otherwise be possible by a single institution. We have expertise in treating patients with these disorders and work at institutions that serve as referral centers for these patients, a crucial factor in the success of these studies. The information obtained will not only be used to guide transplantation for patients with WAS and CGD in the future, but may also be beneficial for patients with other immunodeficiencies and even those with other non-malignant hematologic conditions.

Public Health Relevance

Primary immune deficiencies (PIDs) are rare, life-threatening inherited defects in the immune system. This longitudinal, retrospective and cross-sectional study of Wiskott Aldrich Syndrome and Chronic Granulomatous Disease will provide the basis for designing and implementing prospective clinical trials in order to determine their optimal management.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZRG1-HOP-Y)
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University of California San Francisco
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