Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison
Purpose Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood–brain barrier (BBB) support recommendations that hematopoietic cell t...
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| Veröffentlicht in: | Genetics in medicine 2018-11, Vol.20 (11), p.1423-1429 |
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| creator | Eisengart, Julie B Rudser, Kyle D Xue, Yong Orchard, Paul Miller, Weston Lund, Troy Van der Ploeg, Ans Mercer, Jean Jones, Simon Mengel, Karl Eugen Gökce, Seyfullah Guffon, Nathalie Giugliani, Roberto de Souza, Carolina F M Shapiro, Elsa G Whitley, Chester B |
| description | Purpose
Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood–brain barrier (BBB) support recommendations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics precludes randomized comparison of ERT with HCT, but insight into this comparison is presented with an international cohort of patients with Hurler syndrome who received long-term ERT from a young age.
Methods
Long-term survival and neurologic outcomes were compared among three groups of patients with Hurler syndrome: 18 treated with ERT monotherapy (ERT group), 54 who underwent HCT (HCT group), and 23 who received no therapy (Untreated). All were followed starting before age 5 years. A sensitivity analysis restricted age of treatment below 3 years.
Results
Survival was worse when comparing ERT versus HCT, and Untreated versus ERT. The cumulative incidences of hydrocephalus and cervical spinal cord compression were greater in ERT versus HCT. Findings persisted in the sensitivity analysis.
Conclusion
As newborn screening widens treatment opportunity for Hurler syndrome, this examination of early treatment quantifies some ERT benefit, supports presumptions about BBB impenetrability, and aligns with current guidelines to treat with HCT. |
| doi_str_mv | 10.1038/gim.2018.29 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2012115792</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2012115792</sourcerecordid><originalsourceid>FETCH-LOGICAL-c391t-195641219740f8ddefab508d8c6c601c750f823032d1bee06f39b4f3659bbcaf3</originalsourceid><addsrcrecordid>eNptkMFrFDEUh4NYbK2evEvAi6CzvpfsZJLepKgtLHhpz0Mm87KmzCRrMnPof2-WrQriKeH3vnyP_Bh7g7BBkPrTPswbAag3wjxjF9hKaEAq9bzewehGKoBz9rKUBwDspIAX7FyYFrtOtReMdinum4XyzNO6uDRT4cnz8lgWmoPjyw_K9hBq6lPmN2ueKNdpHHNFr7iNPMT6OtolpGgnPq_TEhwdM15tB5tDSfEVO_N2KvT66bxk91-_3F3fNLvv326vP-8aJw0uDZpWbVGg6bbg9TiSt0MLetROOQXourbGQoIUIw5EoLw0w9ZL1ZphcNbLS_b-5D3k9HOlsvRzKI6myUZKa-lrTQKx7Yyo6Lt_0Ie01n9MlcKt0Uaghkp9OFEup1Iy-f6Qw2zzY4_QH9vva_tHre6FqfTbJ-c6zDT-YX_XXYGPJ6DUUdxT_rv0f75fwm2Pvg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2149892180</pqid></control><display><type>article</type><title>Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Eisengart, Julie B ; Rudser, Kyle D ; Xue, Yong ; Orchard, Paul ; Miller, Weston ; Lund, Troy ; Van der Ploeg, Ans ; Mercer, Jean ; Jones, Simon ; Mengel, Karl Eugen ; Gökce, Seyfullah ; Guffon, Nathalie ; Giugliani, Roberto ; de Souza, Carolina F M ; Shapiro, Elsa G ; Whitley, Chester B</creator><creatorcontrib>Eisengart, Julie B ; Rudser, Kyle D ; Xue, Yong ; Orchard, Paul ; Miller, Weston ; Lund, Troy ; Van der Ploeg, Ans ; Mercer, Jean ; Jones, Simon ; Mengel, Karl Eugen ; Gökce, Seyfullah ; Guffon, Nathalie ; Giugliani, Roberto ; de Souza, Carolina F M ; Shapiro, Elsa G ; Whitley, Chester B</creatorcontrib><description>Purpose
Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood–brain barrier (BBB) support recommendations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics precludes randomized comparison of ERT with HCT, but insight into this comparison is presented with an international cohort of patients with Hurler syndrome who received long-term ERT from a young age.
Methods
Long-term survival and neurologic outcomes were compared among three groups of patients with Hurler syndrome: 18 treated with ERT monotherapy (ERT group), 54 who underwent HCT (HCT group), and 23 who received no therapy (Untreated). All were followed starting before age 5 years. A sensitivity analysis restricted age of treatment below 3 years.
Results
Survival was worse when comparing ERT versus HCT, and Untreated versus ERT. The cumulative incidences of hydrocephalus and cervical spinal cord compression were greater in ERT versus HCT. Findings persisted in the sensitivity analysis.
Conclusion
As newborn screening widens treatment opportunity for Hurler syndrome, this examination of early treatment quantifies some ERT benefit, supports presumptions about BBB impenetrability, and aligns with current guidelines to treat with HCT.</description><identifier>ISSN: 1098-3600</identifier><identifier>ISSN: 1530-0366</identifier><identifier>EISSN: 1530-0366</identifier><identifier>DOI: 10.1038/gim.2018.29</identifier><identifier>PMID: 29517765</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Blood-Brain Barrier ; Child, Preschool ; Enzyme Replacement Therapy - adverse effects ; Enzyme Replacement Therapy - methods ; Female ; Genetic Testing ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic Stem Cell Transplantation - methods ; Human Genetics ; Humans ; Infant ; Infant, Newborn ; Laboratory Medicine ; Male ; Medical screening ; Mucopolysaccharidosis I - diagnosis ; Mucopolysaccharidosis I - physiopathology ; Mucopolysaccharidosis I - therapy ; Neonatal Screening - methods ; Sensitivity analysis ; Stem cell transplantation</subject><ispartof>Genetics in medicine, 2018-11, Vol.20 (11), p.1423-1429</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by-nc-sa/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-195641219740f8ddefab508d8c6c601c750f823032d1bee06f39b4f3659bbcaf3</citedby><cites>FETCH-LOGICAL-c391t-195641219740f8ddefab508d8c6c601c750f823032d1bee06f39b4f3659bbcaf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29517765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eisengart, Julie B</creatorcontrib><creatorcontrib>Rudser, Kyle D</creatorcontrib><creatorcontrib>Xue, Yong</creatorcontrib><creatorcontrib>Orchard, Paul</creatorcontrib><creatorcontrib>Miller, Weston</creatorcontrib><creatorcontrib>Lund, Troy</creatorcontrib><creatorcontrib>Van der Ploeg, Ans</creatorcontrib><creatorcontrib>Mercer, Jean</creatorcontrib><creatorcontrib>Jones, Simon</creatorcontrib><creatorcontrib>Mengel, Karl Eugen</creatorcontrib><creatorcontrib>Gökce, Seyfullah</creatorcontrib><creatorcontrib>Guffon, Nathalie</creatorcontrib><creatorcontrib>Giugliani, Roberto</creatorcontrib><creatorcontrib>de Souza, Carolina F M</creatorcontrib><creatorcontrib>Shapiro, Elsa G</creatorcontrib><creatorcontrib>Whitley, Chester B</creatorcontrib><title>Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison</title><title>Genetics in medicine</title><addtitle>Genet Med</addtitle><addtitle>Genet Med</addtitle><description>Purpose
Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood–brain barrier (BBB) support recommendations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics precludes randomized comparison of ERT with HCT, but insight into this comparison is presented with an international cohort of patients with Hurler syndrome who received long-term ERT from a young age.
Methods
Long-term survival and neurologic outcomes were compared among three groups of patients with Hurler syndrome: 18 treated with ERT monotherapy (ERT group), 54 who underwent HCT (HCT group), and 23 who received no therapy (Untreated). All were followed starting before age 5 years. A sensitivity analysis restricted age of treatment below 3 years.
Results
Survival was worse when comparing ERT versus HCT, and Untreated versus ERT. The cumulative incidences of hydrocephalus and cervical spinal cord compression were greater in ERT versus HCT. Findings persisted in the sensitivity analysis.
Conclusion
As newborn screening widens treatment opportunity for Hurler syndrome, this examination of early treatment quantifies some ERT benefit, supports presumptions about BBB impenetrability, and aligns with current guidelines to treat with HCT.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood-Brain Barrier</subject><subject>Child, Preschool</subject><subject>Enzyme Replacement Therapy - adverse effects</subject><subject>Enzyme Replacement Therapy - methods</subject><subject>Female</subject><subject>Genetic Testing</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Medical screening</subject><subject>Mucopolysaccharidosis I - diagnosis</subject><subject>Mucopolysaccharidosis I - physiopathology</subject><subject>Mucopolysaccharidosis I - therapy</subject><subject>Neonatal Screening - methods</subject><subject>Sensitivity analysis</subject><subject>Stem cell transplantation</subject><issn>1098-3600</issn><issn>1530-0366</issn><issn>1530-0366</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkMFrFDEUh4NYbK2evEvAi6CzvpfsZJLepKgtLHhpz0Mm87KmzCRrMnPof2-WrQriKeH3vnyP_Bh7g7BBkPrTPswbAag3wjxjF9hKaEAq9bzewehGKoBz9rKUBwDspIAX7FyYFrtOtReMdinum4XyzNO6uDRT4cnz8lgWmoPjyw_K9hBq6lPmN2ueKNdpHHNFr7iNPMT6OtolpGgnPq_TEhwdM15tB5tDSfEVO_N2KvT66bxk91-_3F3fNLvv326vP-8aJw0uDZpWbVGg6bbg9TiSt0MLetROOQXourbGQoIUIw5EoLw0w9ZL1ZphcNbLS_b-5D3k9HOlsvRzKI6myUZKa-lrTQKx7Yyo6Lt_0Ie01n9MlcKt0Uaghkp9OFEup1Iy-f6Qw2zzY4_QH9vva_tHre6FqfTbJ-c6zDT-YX_XXYGPJ6DUUdxT_rv0f75fwm2Pvg</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Eisengart, Julie B</creator><creator>Rudser, Kyle D</creator><creator>Xue, Yong</creator><creator>Orchard, Paul</creator><creator>Miller, Weston</creator><creator>Lund, Troy</creator><creator>Van der Ploeg, Ans</creator><creator>Mercer, Jean</creator><creator>Jones, Simon</creator><creator>Mengel, Karl Eugen</creator><creator>Gökce, Seyfullah</creator><creator>Guffon, Nathalie</creator><creator>Giugliani, Roberto</creator><creator>de Souza, Carolina F M</creator><creator>Shapiro, Elsa G</creator><creator>Whitley, Chester B</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20181101</creationdate><title>Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison</title><author>Eisengart, Julie B ; 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Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood–brain barrier (BBB) support recommendations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics precludes randomized comparison of ERT with HCT, but insight into this comparison is presented with an international cohort of patients with Hurler syndrome who received long-term ERT from a young age.
Methods
Long-term survival and neurologic outcomes were compared among three groups of patients with Hurler syndrome: 18 treated with ERT monotherapy (ERT group), 54 who underwent HCT (HCT group), and 23 who received no therapy (Untreated). All were followed starting before age 5 years. A sensitivity analysis restricted age of treatment below 3 years.
Results
Survival was worse when comparing ERT versus HCT, and Untreated versus ERT. The cumulative incidences of hydrocephalus and cervical spinal cord compression were greater in ERT versus HCT. Findings persisted in the sensitivity analysis.
Conclusion
As newborn screening widens treatment opportunity for Hurler syndrome, this examination of early treatment quantifies some ERT benefit, supports presumptions about BBB impenetrability, and aligns with current guidelines to treat with HCT.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>29517765</pmid><doi>10.1038/gim.2018.29</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biomedical and Life Sciences Biomedicine Blood-Brain Barrier Child, Preschool Enzyme Replacement Therapy - adverse effects Enzyme Replacement Therapy - methods Female Genetic Testing Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cell Transplantation - methods Human Genetics Humans Infant Infant, Newborn Laboratory Medicine Male Medical screening Mucopolysaccharidosis I - diagnosis Mucopolysaccharidosis I - physiopathology Mucopolysaccharidosis I - therapy Neonatal Screening - methods Sensitivity analysis Stem cell transplantation |
| title | Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison |
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