Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006-2014 European cohort

Arjan C. Lankester, Benedicte Neven, Nizar Mahlaoui, Erik G.J. von Asmuth, Virginie Courteille, Mikael Alligon, Michael H. Albert, Isabelle Badell Serra, Peter Bader, Dmitry Balashov, Rita Beier, Yves Bertrand, Stephane Blanche, Victoria Bordon, Robbert G. Bredius, Andrew Cant, Marina Cavazzana, Cristina Diaz-de-Heredia, Figen Dogu, Karoline EhlertNatacha Entz-Werle, Anders Fasth, Francesca Ferrua, Alina Ferster, Renata Formankova, Wilhelm Friedrich, Marta Gonzalez-Vicent, Jolanta Gozdzik, Tayfun Güngör, Manfred Hoenig, Aydan Ikinciogullari, Krzysztof Kalwak, Savas Kansoy, Alphan Kupesiz, Arnalda Lanfranchi, Caroline A. Lindemans, Roland Meisel, Gerard Michel, Nuno A.A. Miranda, Jose Moraleda, Despina Moshous, Herbert Pichler, Kanchan Rao, Petr Sedlacek, Mary Slatter, Elena Soncini, Carsten Speckmann, Mikael Sundin, Amos Toren, Kim Vettenranta, Austen Worth, Mehmet A. Yeşilipek, Marco Zecca, Fulvio Porta, Ansgar Schulz, Paul Veys, Alain Fischer, Andrew R. Gennery

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)1744-1754.e8
JournalJournal of Allergy and Clinical Immunology
Volume149
Issue number5
DOIs
StatePublished - May 2022
Externally publishedYes

Keywords

  • SCID
  • conditioning
  • genetic subgroups
  • immune reconstitution
  • pretransplantation infections

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