A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis

Carsten Speckmann, Sam Doerken, Alessandro Aiuti, Michael H. Albert, Waleed Al-Herz, Luis M. Allende, Alessia Scarselli, Tadej Avcin, Ruy Perez-Becker, Caterina Cancrini, Andrew Cant, Silvia Di Cesare, Andrea Finocchi, Alain Fischer, H. Bobby Gaspar, Sujal Ghosh, Andrew Gennery, Kimberly Gilmour, Luis I. González-Granado, Monica Martinez-GalloSophie Hambleton, Fabian Hauck, Manfred Hoenig, Despina Moshous, Benedicte Neven, Tim Niehues, Luigi Notarangelo, Capucine Picard, Nikolaus Rieber, Ansgar Schulz, Klaus Schwarz, Markus G. Seidel, Pere Soler-Palacin, Polina Stepensky, Brigitte Strahm, Thomas Vraetz, Klaus Warnatz, Christine Winterhalter, Austen Worth, Sebastian Fuchs, Annette Uhlmann, Stephan Ehl

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31 Citations (Scopus)

Abstract

© 2016 American Academy of Allergy, Asthma & Immunology 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.
Original languageEnglish
Pages (from-to)1302-1310.e4
JournalJournal of Allergy and Clinical Immunology
Volume139
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Keywords

  • combined immunodeficiency
  • hematopoietic stem cell transplantation
  • natural history
  • T-cell deficiency

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