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Lookup NU author(s): Professor Andrew Cant, Professor Mary Slatter, Professor Andrew GenneryORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 The AuthorsBackground: Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome. Objective: We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome. Methods: HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed. Results: Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P <.001). The 2-year event-free survival (EFS) was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (P <.001). Genetic subgroups did not differ in 2-year OS (P =.1) and EFS (P =.073). In multivariate analysis, pretransplantation infections and use of MMRDs were associated with less favorable OS and EFS. With a median follow-up of 6.2 years (range, 2.0-11.8 years), 73 of 152 patients in the IR cohort were alive and well without Ig dependency. IL-2 receptor gamma chain/Janus kinase 3/IL-7 receptor–deficient SCID, myeloablative conditioning, matched donor HSCT, and naive CD4 T lymphocytes >0.5 × 10e3/μL at +1 year were identified as independent predictors of favorable clinical and immunologic outcome. Conclusion: Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.
Author(s): Lankester AC, Neven B, Mahlaoui N, von Asmuth EGJ, Courteille V, Alligon M, Albert MH, Serra IB, Bader P, Balashov D, Beier R, Bertrand Y, Blanche S, Bordon V, Bredius RG, Cant A, Cavazzana M, Diaz-de-Heredia C, Dogu F, Ehlert K, Entz-Werle N, Fasth A, Ferrua F, Ferster A, Formankova R, Friedrich W, Gonzalez-Vicent M, Gozdzik J, Gungor T, Hoenig M, Ikinciogullari A, Kalwak K, Kansoy S, Kupesiz A, Lanfranchi A, Lindemans CA, Meisel R, Michel G, Miranda NAA, Moraleda J, Moshous D, Pichler H, Rao K, Sedlacek P, Slatter M, Soncini E, Speckmann C, Sundin M, Toren A, Vettenranta K, Worth A, Yesilipek MA, Zecca M, Porta F, Schulz A, Veys P, Fischer A, Gennery AR
Publication type: Article
Publication status: Published
Journal: Journal of Allergy and Clinical Immunology
Year: 2022
Volume: 149
Issue: 5
Pages: 1744-1754.e8
Print publication date: 04/05/2022
Online publication date: 27/10/2021
Acceptance date: 20/10/2021
Date deposited: 14/12/2021
ISSN (print): 0091-6749
ISSN (electronic): 1097-6825
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.jaci.2021.10.017
DOI: 10.1016/j.jaci.2021.10.017
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