Severe Combined Immune Deficiency (SCID) includes a spectrum of lethal genetic disorders resulting in profound deficiencies of T and B cell development and/or function, which render affected patients incapable of mounting protective immune responses against exogenous pathogens. Historically, children afflicted with SCID rarely survived the first year of life, succumbing to severe infections. The first cure of SCID was achieved in 1968 by transplantation of bone marrow (hematopoietic cell transplant - HCT) from an HLA compatible normal sibling, resulting in reconstitution of both T and B cell immunity. Since that time, more than 700 SCID patients in North America have been treated with HCT from matched siblings, haplo-identical parents, or unrelated adult donors or umbilical cord blood. While outcomes are generally good, not all patients survive and multiple patient-, donor- and transplant procedural differences may underlie the prognosis in each case. We have constructed a multi-institutional consortium to study this large cohort of patients, with the goal of identifying prognostic factors and defining optimal treatment approaches.
In Specific Aim 1, we will perform a retrospective analysis of patients with the different forms of SCID who have received HCT at the participating institutions. We will analyze the impact that patient-, donor-, and transplantrelated factors have on long-term outcome. This study will also provide the first multicenter analysis of the effects of SCID genotype on the outcome of transplant.
In Specific Aim 2, we will perform a cross-sectional analysis of long-term survivors after HCT for SCID, to characterize current level of T, B and NK cell chimerism and function, and clinical status in terms of health, growth and both physical and neurocognitive development. We will then analyze these results in relation to information gathered in the retrospective study to determine whether and to what degree SCID genotype, type of transplant applied or other clinical variables contribute to the patient's long-term outcome. These studies will produce important information on the outcomes of HCT for SCID and guide future clinical trials.
Primary immune deficiencies (PIDs) are rare, life-threatening inherited defects in the immune system. This retrospective and cross-sectional study of severe combined immunodeficiency disease (SCID) will help accomplish the Primary Immune Deficiency Treatment Consortium (PIDTC)'s overall objective of elucidating the prognostic factors for patients with SCID undergoing HCT to lead to the development of future therapeutic clinical trials.
|Long-Boyle, Janel R; Savic, Rada; Yan, Shirley et al. (2015) Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use. Ther Drug Monit 37:236-45|
|Haddad, Elie; Allakhverdi, Zoulfia; Griffith, Linda M et al. (2014) Survey on retransplantation criteria for patients with severe combined immunodeficiency. J Allergy Clin Immunol 133:597-9|
|Shearer, William T; Dunn, Elizabeth; Notarangelo, Luigi D et al. (2014) Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol 133:1092-8|
|Dvorak, Christopher C; Hassan, Amel; Slatter, Mary A et al. (2014) Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. J Allergy Clin Immunol 134:935-943.e15|
|Lee, Yu Nee; Frugoni, Francesco; Dobbs, Kerry et al. (2014) A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency. J Allergy Clin Immunol 133:1099-108|
|Pai, Sung-Yun; Cowan, Morton J (2014) Stem cell transplantation for primary immunodeficiency diseases: the North American experience. Curr Opin Allergy Clin Immunol 14:521-6|
|Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D et al. (2014) Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol 133:335-47|
|Medical Advisory Committee of the Immune Deficiency Foundation; Shearer, William T; Fleisher, Thomas A et al. (2014) Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol 133:961-6|
|Chinen, Javier; Notarangelo, Luigi D; Shearer, William T (2014) Advances in basic and clinical immunology in 2013. J Allergy Clin Immunol 133:967-76|
|Pai, Sung-Yun; Logan, Brent R; Griffith, Linda M et al. (2014) Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med 371:434-46|
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