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...
Autores principales: | , , , , , , |
---|---|
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 |