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 Ehlert; Natacha 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

doi:10.1016/j.jaci.2021.10.017

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

^*Corresponding author for this work

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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 × 10^e3/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 language	English
Pages (from-to)	1744-1754.e8
Journal	Journal of Allergy and Clinical Immunology
Volume	149
Issue number	5
DOIs	https://doi.org/10.1016/j.jaci.2021.10.017
Publication status	Published - May 2022

Keywords

conditioning
genetic subgroups
immune reconstitution
pretransplantation infections
SCID

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Lankester, A. C., Neven, B., Mahlaoui, N., von Asmuth, E. G. J., Courteille, V., Alligon, M., Albert, M. H., Serra, I. B., Bader, P., Balashov, D., Beier, R., Bertrand, Y., Blanche, S., Bordon, V., Bredius, R. G., Cant, A., Cavazzana, M., Diaz-de-Heredia, C., Dogu, F., ... Vettenranta, K. (2022). Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006-2014 European cohort. Journal of Allergy and Clinical Immunology, 149(5), 1744-1754.e8. https://doi.org/10.1016/j.jaci.2021.10.017

@article{af2d691e66e94aa884b78d29473bf9b9,

title = "Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006-2014 European cohort",

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.",

keywords = "conditioning, genetic subgroups, immune reconstitution, pretransplantation infections, SCID",

author = "Lankester, {Arjan C.} and Benedicte Neven and Nizar Mahlaoui and {von Asmuth}, {Erik G.J.} and Virginie Courteille and Mikael Alligon and Albert, {Michael H.} and Serra, {Isabelle Badell} and Peter Bader and Dmitry Balashov and Rita Beier and Yves Bertrand and Stephane Blanche and Victoria Bordon and Bredius, {Robbert G.} and Andrew Cant and Marina Cavazzana and Cristina Diaz-de-Heredia and Figen Dogu and Karoline Ehlert and Natacha Entz-Werle and Anders Fasth and Francesca Ferrua and Alina Ferster and Renata Formankova and Wilhelm Friedrich and Marta Gonzalez-Vicent and Jolanta Gozdzik and Tayfun G{\"u}ng{\"o}r and Manfred Hoenig and Aydan Ikinciogullari and Krzysztof Kalwak and Savas Kansoy and Alphan Kupesiz and Arnalda Lanfranchi and Lindemans, {Caroline A.} and Roland Meisel and Gerard Michel and Miranda, {Nuno A.A.} and Jose Moraleda and Despina Moshous and Herbert Pichler and Kanchan Rao and Petr Sedlacek and Mary Slatter and Elena Soncini and Carsten Speckmann and Mikael Sundin and Amos Toren and Kim Vettenranta",

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: {\textcopyright} 2021 The Authors",

year = "2022",

month = may,

doi = "10.1016/j.jaci.2021.10.017",

language = "English",

volume = "149",

pages = "1744--1754.e8",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "5",

}

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, Güngör, 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 2022, 'Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006-2014 European cohort', Journal of Allergy and Clinical Immunology, vol. 149, no. 5, pp. 1744-1754.e8. https://doi.org/10.1016/j.jaci.2021.10.017

TY - JOUR

T1 - Hematopoietic cell transplantation in severe combined immunodeficiency

T2 - The SCETIDE 2006-2014 European cohort

AU - Lankester, Arjan C.

AU - Neven, Benedicte

AU - Mahlaoui, Nizar

AU - von Asmuth, Erik G.J.

AU - Courteille, Virginie

AU - Alligon, Mikael

AU - Albert, Michael H.

AU - Serra, Isabelle Badell

AU - Bader, Peter

AU - Balashov, Dmitry

AU - Beier, Rita

AU - Bertrand, Yves

AU - Blanche, Stephane

AU - Bordon, Victoria

AU - Bredius, Robbert G.

AU - Cant, Andrew

AU - Cavazzana, Marina

AU - Diaz-de-Heredia, Cristina

AU - Dogu, Figen

AU - Ehlert, Karoline

AU - Entz-Werle, Natacha

AU - Fasth, Anders

AU - Ferrua, Francesca

AU - Ferster, Alina

AU - Formankova, Renata

AU - Friedrich, Wilhelm

AU - Gonzalez-Vicent, Marta

AU - Gozdzik, Jolanta

AU - Güngör, Tayfun

AU - Hoenig, Manfred

AU - Ikinciogullari, Aydan

AU - Kalwak, Krzysztof

AU - Kansoy, Savas

AU - Kupesiz, Alphan

AU - Lanfranchi, Arnalda

AU - Lindemans, Caroline A.

AU - Meisel, Roland

AU - Michel, Gerard

AU - Miranda, Nuno A.A.

AU - Moraleda, Jose

AU - Moshous, Despina

AU - Pichler, Herbert

AU - Rao, Kanchan

AU - Sedlacek, Petr

AU - Slatter, Mary

AU - Soncini, Elena

AU - Speckmann, Carsten

AU - Sundin, Mikael

AU - Toren, Amos

AU - Vettenranta, Kim

N1 - 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

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

KW - conditioning

KW - genetic subgroups

KW - immune reconstitution

KW - pretransplantation infections

KW - SCID

UR - http://www.scopus.com/inward/record.url?scp=85119599905&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2021.10.017

DO - 10.1016/j.jaci.2021.10.017

M3 - Article

AN - SCOPUS:85119599905

SN - 0091-6749

VL - 149

SP - 1744-1754.e8

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 5

ER -

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

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