Cargando…

Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders

To evaluate the relationship between knowledge of genetic diagnosis before HSCT and outcome, we reviewed all HSCTs for primary immune deficiencies (PID) performed at UCSF from 2007 through 2018. SCID, a distinct entity identified since 2010 in California by newborn screening and treated early, was c...

Descripción completa

Detalles Bibliográficos
Autores principales: Forlanini, Federica, Chan, Alice, Dara, Jasmeen, Dvorak, Christopher C., Cowan, Morton J., Puck, Jennifer M., Dorsey, Morna J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958161/
https://www.ncbi.nlm.nih.gov/pubmed/36495401
http://dx.doi.org/10.1007/s10875-022-01403-5
_version_ 1784894966966779904
author Forlanini, Federica
Chan, Alice
Dara, Jasmeen
Dvorak, Christopher C.
Cowan, Morton J.
Puck, Jennifer M.
Dorsey, Morna J.
author_facet Forlanini, Federica
Chan, Alice
Dara, Jasmeen
Dvorak, Christopher C.
Cowan, Morton J.
Puck, Jennifer M.
Dorsey, Morna J.
author_sort Forlanini, Federica
collection PubMed
description To evaluate the relationship between knowledge of genetic diagnosis before HSCT and outcome, we reviewed all HSCTs for primary immune deficiencies (PID) performed at UCSF from 2007 through 2018. SCID, a distinct entity identified since 2010 in California by newborn screening and treated early, was considered separately. The underlying genetic condition was known at the time of HSCT in 85% of cases. Graft failure was less frequent in patients with a genetic diagnosis (19% with a genetic diagnosis versus 47% without, p = 0.020). Furthermore, event-free survival and overall survival (OS) at 5 years were better for those with a genetic diagnosis (78% with versus 44% without, p = 0.006; and 93% versus 60% without, p = 0.0002, respectively). OS at 5 years was superior for known-genotype patients with both SCID (p = 0.010) and non-SCID PID (p = 0.010). There was no difference in OS between HSCT done in 2007–2010 compared to more recently (p = 0.19). These data suggest that outcomes of HSCT for PID with known genotype may reflect specific experience and literature, or that a substantial proportion of patients with PID of undetermined genotype may have had underlying conditions for which HSCT may carry greater risk. The higher rate of graft failure in PID with unknown genotype may be in part explained by insufficient conditioning, which in turn could be dictated by compromised organ function in patients undergoing HSCT late in the course. Widespread availability of PID gene sequencing as standard care can provide genetic diagnoses for most patients with PID prior to HSCT, permitting optimization of transplant approach. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10875-022-01403-5.
format Online
Article
Text
id pubmed-9958161
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-99581612023-02-26 Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders Forlanini, Federica Chan, Alice Dara, Jasmeen Dvorak, Christopher C. Cowan, Morton J. Puck, Jennifer M. Dorsey, Morna J. J Clin Immunol Original Article To evaluate the relationship between knowledge of genetic diagnosis before HSCT and outcome, we reviewed all HSCTs for primary immune deficiencies (PID) performed at UCSF from 2007 through 2018. SCID, a distinct entity identified since 2010 in California by newborn screening and treated early, was considered separately. The underlying genetic condition was known at the time of HSCT in 85% of cases. Graft failure was less frequent in patients with a genetic diagnosis (19% with a genetic diagnosis versus 47% without, p = 0.020). Furthermore, event-free survival and overall survival (OS) at 5 years were better for those with a genetic diagnosis (78% with versus 44% without, p = 0.006; and 93% versus 60% without, p = 0.0002, respectively). OS at 5 years was superior for known-genotype patients with both SCID (p = 0.010) and non-SCID PID (p = 0.010). There was no difference in OS between HSCT done in 2007–2010 compared to more recently (p = 0.19). These data suggest that outcomes of HSCT for PID with known genotype may reflect specific experience and literature, or that a substantial proportion of patients with PID of undetermined genotype may have had underlying conditions for which HSCT may carry greater risk. The higher rate of graft failure in PID with unknown genotype may be in part explained by insufficient conditioning, which in turn could be dictated by compromised organ function in patients undergoing HSCT late in the course. Widespread availability of PID gene sequencing as standard care can provide genetic diagnoses for most patients with PID prior to HSCT, permitting optimization of transplant approach. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10875-022-01403-5. Springer US 2022-12-10 2023 /pmc/articles/PMC9958161/ /pubmed/36495401 http://dx.doi.org/10.1007/s10875-022-01403-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Forlanini, Federica
Chan, Alice
Dara, Jasmeen
Dvorak, Christopher C.
Cowan, Morton J.
Puck, Jennifer M.
Dorsey, Morna J.
Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders
title Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders
title_full Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders
title_fullStr Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders
title_full_unstemmed Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders
title_short Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders
title_sort impact of genetic diagnosis on the outcome of hematopoietic stem cell transplant in primary immunodeficiency disorders
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958161/
https://www.ncbi.nlm.nih.gov/pubmed/36495401
http://dx.doi.org/10.1007/s10875-022-01403-5
work_keys_str_mv AT forlaninifederica impactofgeneticdiagnosisontheoutcomeofhematopoieticstemcelltransplantinprimaryimmunodeficiencydisorders
AT chanalice impactofgeneticdiagnosisontheoutcomeofhematopoieticstemcelltransplantinprimaryimmunodeficiencydisorders
AT darajasmeen impactofgeneticdiagnosisontheoutcomeofhematopoieticstemcelltransplantinprimaryimmunodeficiencydisorders
AT dvorakchristopherc impactofgeneticdiagnosisontheoutcomeofhematopoieticstemcelltransplantinprimaryimmunodeficiencydisorders
AT cowanmortonj impactofgeneticdiagnosisontheoutcomeofhematopoieticstemcelltransplantinprimaryimmunodeficiencydisorders
AT puckjenniferm impactofgeneticdiagnosisontheoutcomeofhematopoieticstemcelltransplantinprimaryimmunodeficiencydisorders
AT dorseymornaj impactofgeneticdiagnosisontheoutcomeofhematopoieticstemcelltransplantinprimaryimmunodeficiencydisorders