A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children with SCID Disorders

University Of California, San Francisco, San Francisco CA

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Abstract

The ultimate goal of this project is to prospectively study newly diagnosed infants and children born in North America with Severe Combined Immunodeficiency (SCID), a very rare disorder that requires hematopoietic cell transplantafion (HCT), gene therapy (GT) or enzyme replacement therapy (ERT) for survival. We are addressing quesfions that can only be answered prospectively, and are studying an increasingly interesfing group of atypical SCID patients who are leaky and/or who have Omenn syndrome. Finally, we will make every effort to identify a genotype for all eligible SCID patients using state-of-the-art methods to define the molecular defects and we will serially characterize key parameters of immunological reconstitution and lineage-specific chimerism. We began enrolling pafients into this study in 2010 and have accrued -40% of our goal which should be reached in 2017. The specific aims of this study are: Specific Aim 1) To determine the effects of patient-related factors on early survival, time to and extent of immune reconstitution and early clinical outcome after HCT for SCID or Atypical SCID. Specific Aim 2) To determine the effects of donorand transplant-related factors on early survival, fime to immune reconstitufion and early clinical outcome after HCT for SCID or atypical SCID. This project will help accomplish the proposal's overall objective of improving definitive therapy for SCID by comparing relafively short term outcomes ofthe different treatment approaches currenfiy being employed for HCT for SCID in a uniformly and comprehensively evaluated cohort of pafients. Uniquely, the cohort will contain a significant number of pafients with 1) SCID diagnosed by newborn screening, and 2) pafients with atypical SCID. It will define early biomarkers that predict survival, the kinefics of immune reconstitufion, and the risk for graft versus host disease (GVHD) and/or post- HCT autoimmune disease. The results of this prospective study will address questions that cannot be answered by retrospective or cross-sectional studies and will provide the basis for clinical trials aimed at defining strategies to optimize survival and long-term immune reconstitufion while reducing complicafions after HCT for SCID.