Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006-2014 European cohort
Lankester, Arjan C.; Neven, Benedicte; Mahlaoui, Nizar; von Asmuth, Erik G.J.; Courteille, Virginie; Alligon, Mikael; Albert, Michael H.; Serra, Isabelle Badell; Bader, Peter; Balashov, Dmitry; Beier, Rita; Bertrand, Yves; Blanche, Stephane; Bordon, Victoria; Bredius, Robbert G.; Cant, Andrew; Cavazzana, Marina; Diaz-de-Heredia, Cristina; Dogu, Figen; Ehlert, Karoline; Entz-Werle, Natacha; Fasth, Anders; Ferrua, Francesca; Ferster, Alina; Formankova, Renata; Friedrich, Wilhelm; Gonzalez-Vicent, Marta; Gozdzik, Jolanta; Güngör, Tayfun; Hoenig, Manfred; Ikinciogullari, Aydan; Kalwak, Krzysztof; Kansoy, Savas; Kupesiz, Alphan; Lanfranchi, Arnalda; Lindemans, Caroline A.; Meisel, Roland; Michel, Gerard; Miranda, Nuno A.A.; Moraleda, Jose; Moshous, Despina; Pichler, Herbert; Rao, Kanchan; Sedlacek, Petr; Slatter, Mary; Soncini, Elena; Speckmann, Carsten; Sundin, Mikael; Toren, Amos; Vettenranta, Kim
(2022) Journal of Allergy and Clinical Immunology, volume 149, issue 5, pp. 1744 - 1754.e8
(Article)
Abstract
Background: 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
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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.
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Keywords: conditioning, genetic subgroups, immune reconstitution, pretransplantation infections, SCID, Immunology and Allergy, Immunology
ISSN: 0091-6749
Publisher: Mosby Inc.
Note: Funding Information: E. G. J. von Asmuth received support from the Dutch Rare Disease Foundation/Stichting Zeldzame Ziekten Fonds. Funding Information: E. G. J. von Asmuth received support from the Dutch Rare Disease Foundation / Stichting Zeldzame Ziekten Fonds . Publisher Copyright: © 2021 The Authors
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