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, No. 4: pp. 1302-1310 |
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.
Item Type: | Journal article |
---|---|
Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 0091-6749 |
Language: | English |
ID Code: | 51727 |
Deposited On: | 14. Jun 2018 09:47 |
Last Modified: | 04. Nov 2020 13:30 |
- BASE
- 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
- Google Scholar
- 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