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Speckmann, Carsten; Doerken, Sam; Aiuti, Alessandro; Albert, Michael H.; Al-Herz, Waleed; Allende, Luis M.; Scarselli, Alessia; Avcin, Tadej; Perez-Becker, Ruy; Cancrini, Caterina; Cant, Andrew; Cesare, Silvia di; Finocchi, Andrea; Fischer, Alain; Gaspar, H. Bobby; Ghosh, Sujal; Gennery, Andrew; Gilmour, Kimberly; Gonzalez-Granado, Luis I.; Martinez-Gallo, Monica; Hambleton, Sophie; Hauck, Fabian; Hoenig, Manfred; Moshous, Despina; Neven, Benedicte; Niehues, Tim; Notarangelo, Luigi; Picard, Capucine; Rieber, Nikolaus; Schulz, Ansgar; Schwarz, Klaus; Seidel, Markus G.; Soler-Palacin, Pere; Stepensky, Polina; Strahm, Brigitte; Vraetz, Thomas; Warnatz, Klaus; Winterhalter, Christine; Worth, Austen; Fuchs, Sebastian; Uhlmann, Annette; Ehl, Stephan (2017): A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis. In: Journal of Allergy and Clinical Immunology, Vol. 139, Nr. 4: S. 1302-1310
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Abstract

Background: Absent T-cell immunity resulting in life-threatening infections provides a clear rationale for hematopoetic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency ( SCID). Combined immunodeficiencies (CIDs) and "atypical" SCID show reduced, not absent T-cell immunity. If associated with infections or autoimmunity, they represent profound combined immunodeficiency (P-CID), for which outcome data are insufficient for unambiguous early transplant decisions. Objectives: We sought to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. Methods: In this prospective and retrospective observational study, we recruited nontransplanted patients with P-CID aged 1 to 16 years to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. Results: A total of 51 patients were recruited (median age, 9.6 years). Thirteen of 51 had a genetic diagnosis of "atypical" SCID and 14 of 51 of CID. About half of the patients had less than 10% naive T cells, reduced/absent T-cell proliferation, and at least 1 significant clinical event/year, demonstrating their profound immunodeficiency. Nineteen patients (37%) underwent transplantation within 1 year of enrolment, and 5 of 51 patients died. Analysis of the HSCT decisions revealed the anticipated heterogeneity, favoring an ongoing prospective matched-pair analysis of patients with similar disease severity with or without transplantation. Importantly, so far neither the genetic diagnosis nor basic measurements of T-cell immunity were good predictors of disease evolution. Conclusions: The P-CID study for the first time characterizes a group of patients with nontypical SCID T-cell deficiencies from a therapeutic perspective. Because genetic and basic T-cell parameters provide limited guidance, prospective data from this study will be a helpful resource for guiding the difficult HSCT decisions in patients with P-CID.