Speckmann, C;
Doerken, S;
Aiuti, A;
Albert, MH;
Al-Herz, W;
Allende, LM;
Scarselli, A;
... P-CID study of the Inborn Errors Working Party of the EBMT, .; + view all
(2017)
A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis.
Journal of Allergy and Clinical Immunology
, 139
(4)
1302-1310.e4.
10.1016/j.jaci.2016.07.040.
Preview |
Text
nihms-1002622.pdf - Accepted Version Download (2MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jaci.2016.07.040 |
| Publisher version: | https://doi.org/10.1016/j.jaci.2016.07.040 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | T-cell deficiency, combined immunodeficiency, hematopoietic stem cell transplantation, natural history |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10076602 |
Loading...
Loading...Loading...Loading...Archive Staff Only
 |
View Item |
