Impact of total body irradiation‐ vs chemotherapy‐based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia

The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo‐HCT) is unknown. We studied the outcomes of total body irradiation (TBI) vs chemotherapy (CT) based MAC regimens in acute myeloid leukemia (AML) patients. The study included...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:American journal of hematology 2020-10, Vol.95 (10), p.1200-1208
Hauptverfasser: Dholaria, Bhagirathbhai, Labopin, Myriam, Angelucci, Emanuele, Ciceri, Fabio, Diez‐Martin, Jose L., Bruno, Benedetto, Sica, Simona, Koc, Yener, Gülbas, Zafer, Schmid, Christoph, Blaise, Didier, Carella, Angelo Michele, Visani, Guiseppe, Savani, Bipin N., Nagler, Arnon, Mohty, Mohamad
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1208
container_issue 10
container_start_page 1200
container_title American journal of hematology
container_volume 95
creator Dholaria, Bhagirathbhai
Labopin, Myriam
Angelucci, Emanuele
Ciceri, Fabio
Diez‐Martin, Jose L.
Bruno, Benedetto
Sica, Simona
Koc, Yener
Gülbas, Zafer
Schmid, Christoph
Blaise, Didier
Carella, Angelo Michele
Visani, Guiseppe
Savani, Bipin N.
Nagler, Arnon
Mohty, Mohamad
description The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo‐HCT) is unknown. We studied the outcomes of total body irradiation (TBI) vs chemotherapy (CT) based MAC regimens in acute myeloid leukemia (AML) patients. The study included 1008 patients who underwent first haplo‐HCT with post‐transplant cyclophosphamide, following TBI (N = 89, 9%) or CT (n = 919, 91%) based MAC. Patients in the TBI cohort were younger (median age, 38 vs 47 years, P
doi_str_mv 10.1002/ajh.25934
format Article
fullrecord <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_03152832v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2423515024</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3994-ca5a4dc2d65742dd1f0da743e0ee458e6c6c813cbdbd5bf53272cdfcc0459a883</originalsourceid><addsrcrecordid>eNp1kcFu1DAQhiMEEkvhwBtY4gKHbW3HzibHVQVs0Upc4BxN7EnjxYmD7WyVG4_A0_SB-iQ4DQIJiZPHo2_-f0Z_lr1m9JJRyq_g1F1yWeXiSbZhtCq2ZSH502xD84KlmlbPsxchnChlTJR0k93f9COoSFxLootgSeP0TIz3oA1E44aHHz_JORDVYe9ihx7GObUaCKhJP6N10NgEnpEoN2izjJjhlriBuCkq12NYtDsYrTMah2hUMkliEN3oDKY_UWgtiR6GMFoY4qMtaZ0noKaIq8stDm4KxOL0DXsDL7NnLdiAr36_F9nXD--_XB-2x88fb673x63Kq0psFUgQWnFdyJ3gWrOWatiJHCmikCUWqlAly1WjGy2bVuZ8x5VulaJCVlCW-UX2btXtwNajNz34uXZg6sP-WC89mjPJy5yfWWLfruzo3fcJQ6x7E5bbYMC0e80FzyWTlIuEvvkHPbnJD-mSRAlBaVVK-ddceReCx_bPBozWS9p1Srt-TDuxVyt7ZyzO_wfr_afDOvELZNWy6g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2444009855</pqid></control><display><type>article</type><title>Impact of total body irradiation‐ vs chemotherapy‐based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia</title><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><creator>Dholaria, Bhagirathbhai ; Labopin, Myriam ; Angelucci, Emanuele ; Ciceri, Fabio ; Diez‐Martin, Jose L. ; Bruno, Benedetto ; Sica, Simona ; Koc, Yener ; Gülbas, Zafer ; Schmid, Christoph ; Blaise, Didier ; Carella, Angelo Michele ; Visani, Guiseppe ; Savani, Bipin N. ; Nagler, Arnon ; Mohty, Mohamad</creator><creatorcontrib>Dholaria, Bhagirathbhai ; Labopin, Myriam ; Angelucci, Emanuele ; Ciceri, Fabio ; Diez‐Martin, Jose L. ; Bruno, Benedetto ; Sica, Simona ; Koc, Yener ; Gülbas, Zafer ; Schmid, Christoph ; Blaise, Didier ; Carella, Angelo Michele ; Visani, Guiseppe ; Savani, Bipin N. ; Nagler, Arnon ; Mohty, Mohamad</creatorcontrib><description>The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo‐HCT) is unknown. We studied the outcomes of total body irradiation (TBI) vs chemotherapy (CT) based MAC regimens in acute myeloid leukemia (AML) patients. The study included 1008 patients who underwent first haplo‐HCT with post‐transplant cyclophosphamide, following TBI (N = 89, 9%) or CT (n = 919, 91%) based MAC. Patients in the TBI cohort were younger (median age, 38 vs 47 years, P &lt; .01) and more likely to receive BM graft (57% vs 43%, P = .01). Two‐year overall chronic GVHD (cGVHD) incidence was 42% vs 27% (P &lt; .01) and extensive cGVHD incidence was 9% vs 12% (P = .33) in TBI and CT cohorts, respectively. Graft failure was reported in two (2%) TBI‐ and 65 (7%) CT‐MAC recipients (P = .08). Death from veno‐occlusive disease was reported in one (3%) TBI and 11 (3%) CT patients who died during the study period. In the multivariate analysis, TBI was associated with increased risk for overall cGVHD (hazard ratio = 1.95, 95% confidence interval:1.2‐3.1, P &lt; .01) compared to CT‐based MAC. The choice of conditioning regimen did not impact relapse incidence, leukemia‐free survival, non‐relapse mortality, overall survival or GVHD‐relapse‐free survival in multivariate analysis. In conclusion, major transplant outcomes were not statistically different between TBI‐based MAC and CT‐based MAC in patients with AML after haplo‐HCT/PTCy.</description><identifier>ISSN: 0361-8609</identifier><identifier>EISSN: 1096-8652</identifier><identifier>DOI: 10.1002/ajh.25934</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley &amp; Sons, Inc</publisher><subject>Acute myeloid leukemia ; Chemotherapy ; Cyclophosphamide ; Graft rejection ; Graft-versus-host reaction ; Grafts ; Hematology ; Immunology ; Leukemia ; Life Sciences ; Multivariate analysis ; Myeloid leukemia ; Radiation ; Stem cell transplantation ; Transplantation ; Transplants &amp; implants</subject><ispartof>American journal of hematology, 2020-10, Vol.95 (10), p.1200-1208</ispartof><rights>2020 Wiley Periodicals LLC</rights><rights>2020 Wiley Periodicals LLC.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3994-ca5a4dc2d65742dd1f0da743e0ee458e6c6c813cbdbd5bf53272cdfcc0459a883</citedby><cites>FETCH-LOGICAL-c3994-ca5a4dc2d65742dd1f0da743e0ee458e6c6c813cbdbd5bf53272cdfcc0459a883</cites><orcidid>0000-0003-2371-3655 ; 0000-0002-6512-6080 ; 0000-0002-0763-1265 ; 0000-0001-8536-7781 ; 0000-0002-7264-808X ; 0000-0001-7070-487X ; 0000-0003-4514-4748 ; 0000-0003-0873-0123 ; 0000-0002-3304-9965</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fajh.25934$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fajh.25934$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,777,781,882,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttps://amu.hal.science/hal-03152832$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Dholaria, Bhagirathbhai</creatorcontrib><creatorcontrib>Labopin, Myriam</creatorcontrib><creatorcontrib>Angelucci, Emanuele</creatorcontrib><creatorcontrib>Ciceri, Fabio</creatorcontrib><creatorcontrib>Diez‐Martin, Jose L.</creatorcontrib><creatorcontrib>Bruno, Benedetto</creatorcontrib><creatorcontrib>Sica, Simona</creatorcontrib><creatorcontrib>Koc, Yener</creatorcontrib><creatorcontrib>Gülbas, Zafer</creatorcontrib><creatorcontrib>Schmid, Christoph</creatorcontrib><creatorcontrib>Blaise, Didier</creatorcontrib><creatorcontrib>Carella, Angelo Michele</creatorcontrib><creatorcontrib>Visani, Guiseppe</creatorcontrib><creatorcontrib>Savani, Bipin N.</creatorcontrib><creatorcontrib>Nagler, Arnon</creatorcontrib><creatorcontrib>Mohty, Mohamad</creatorcontrib><title>Impact of total body irradiation‐ vs chemotherapy‐based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia</title><title>American journal of hematology</title><description>The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo‐HCT) is unknown. We studied the outcomes of total body irradiation (TBI) vs chemotherapy (CT) based MAC regimens in acute myeloid leukemia (AML) patients. The study included 1008 patients who underwent first haplo‐HCT with post‐transplant cyclophosphamide, following TBI (N = 89, 9%) or CT (n = 919, 91%) based MAC. Patients in the TBI cohort were younger (median age, 38 vs 47 years, P &lt; .01) and more likely to receive BM graft (57% vs 43%, P = .01). Two‐year overall chronic GVHD (cGVHD) incidence was 42% vs 27% (P &lt; .01) and extensive cGVHD incidence was 9% vs 12% (P = .33) in TBI and CT cohorts, respectively. Graft failure was reported in two (2%) TBI‐ and 65 (7%) CT‐MAC recipients (P = .08). Death from veno‐occlusive disease was reported in one (3%) TBI and 11 (3%) CT patients who died during the study period. In the multivariate analysis, TBI was associated with increased risk for overall cGVHD (hazard ratio = 1.95, 95% confidence interval:1.2‐3.1, P &lt; .01) compared to CT‐based MAC. The choice of conditioning regimen did not impact relapse incidence, leukemia‐free survival, non‐relapse mortality, overall survival or GVHD‐relapse‐free survival in multivariate analysis. In conclusion, major transplant outcomes were not statistically different between TBI‐based MAC and CT‐based MAC in patients with AML after haplo‐HCT/PTCy.</description><subject>Acute myeloid leukemia</subject><subject>Chemotherapy</subject><subject>Cyclophosphamide</subject><subject>Graft rejection</subject><subject>Graft-versus-host reaction</subject><subject>Grafts</subject><subject>Hematology</subject><subject>Immunology</subject><subject>Leukemia</subject><subject>Life Sciences</subject><subject>Multivariate analysis</subject><subject>Myeloid leukemia</subject><subject>Radiation</subject><subject>Stem cell transplantation</subject><subject>Transplantation</subject><subject>Transplants &amp; implants</subject><issn>0361-8609</issn><issn>1096-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kcFu1DAQhiMEEkvhwBtY4gKHbW3HzibHVQVs0Upc4BxN7EnjxYmD7WyVG4_A0_SB-iQ4DQIJiZPHo2_-f0Z_lr1m9JJRyq_g1F1yWeXiSbZhtCq2ZSH502xD84KlmlbPsxchnChlTJR0k93f9COoSFxLootgSeP0TIz3oA1E44aHHz_JORDVYe9ihx7GObUaCKhJP6N10NgEnpEoN2izjJjhlriBuCkq12NYtDsYrTMah2hUMkliEN3oDKY_UWgtiR6GMFoY4qMtaZ0noKaIq8stDm4KxOL0DXsDL7NnLdiAr36_F9nXD--_XB-2x88fb673x63Kq0psFUgQWnFdyJ3gWrOWatiJHCmikCUWqlAly1WjGy2bVuZ8x5VulaJCVlCW-UX2btXtwNajNz34uXZg6sP-WC89mjPJy5yfWWLfruzo3fcJQ6x7E5bbYMC0e80FzyWTlIuEvvkHPbnJD-mSRAlBaVVK-ddceReCx_bPBozWS9p1Srt-TDuxVyt7ZyzO_wfr_afDOvELZNWy6g</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>Dholaria, Bhagirathbhai</creator><creator>Labopin, Myriam</creator><creator>Angelucci, Emanuele</creator><creator>Ciceri, Fabio</creator><creator>Diez‐Martin, Jose L.</creator><creator>Bruno, Benedetto</creator><creator>Sica, Simona</creator><creator>Koc, Yener</creator><creator>Gülbas, Zafer</creator><creator>Schmid, Christoph</creator><creator>Blaise, Didier</creator><creator>Carella, Angelo Michele</creator><creator>Visani, Guiseppe</creator><creator>Savani, Bipin N.</creator><creator>Nagler, Arnon</creator><creator>Mohty, Mohamad</creator><general>John Wiley &amp; Sons, Inc</general><general>Wiley Subscription Services, Inc</general><general>Wiley</general><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-2371-3655</orcidid><orcidid>https://orcid.org/0000-0002-6512-6080</orcidid><orcidid>https://orcid.org/0000-0002-0763-1265</orcidid><orcidid>https://orcid.org/0000-0001-8536-7781</orcidid><orcidid>https://orcid.org/0000-0002-7264-808X</orcidid><orcidid>https://orcid.org/0000-0001-7070-487X</orcidid><orcidid>https://orcid.org/0000-0003-4514-4748</orcidid><orcidid>https://orcid.org/0000-0003-0873-0123</orcidid><orcidid>https://orcid.org/0000-0002-3304-9965</orcidid></search><sort><creationdate>202010</creationdate><title>Impact of total body irradiation‐ vs chemotherapy‐based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia</title><author>Dholaria, Bhagirathbhai ; Labopin, Myriam ; Angelucci, Emanuele ; Ciceri, Fabio ; Diez‐Martin, Jose L. ; Bruno, Benedetto ; Sica, Simona ; Koc, Yener ; Gülbas, Zafer ; Schmid, Christoph ; Blaise, Didier ; Carella, Angelo Michele ; Visani, Guiseppe ; Savani, Bipin N. ; Nagler, Arnon ; Mohty, Mohamad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3994-ca5a4dc2d65742dd1f0da743e0ee458e6c6c813cbdbd5bf53272cdfcc0459a883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute myeloid leukemia</topic><topic>Chemotherapy</topic><topic>Cyclophosphamide</topic><topic>Graft rejection</topic><topic>Graft-versus-host reaction</topic><topic>Grafts</topic><topic>Hematology</topic><topic>Immunology</topic><topic>Leukemia</topic><topic>Life Sciences</topic><topic>Multivariate analysis</topic><topic>Myeloid leukemia</topic><topic>Radiation</topic><topic>Stem cell transplantation</topic><topic>Transplantation</topic><topic>Transplants &amp; implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dholaria, Bhagirathbhai</creatorcontrib><creatorcontrib>Labopin, Myriam</creatorcontrib><creatorcontrib>Angelucci, Emanuele</creatorcontrib><creatorcontrib>Ciceri, Fabio</creatorcontrib><creatorcontrib>Diez‐Martin, Jose L.</creatorcontrib><creatorcontrib>Bruno, Benedetto</creatorcontrib><creatorcontrib>Sica, Simona</creatorcontrib><creatorcontrib>Koc, Yener</creatorcontrib><creatorcontrib>Gülbas, Zafer</creatorcontrib><creatorcontrib>Schmid, Christoph</creatorcontrib><creatorcontrib>Blaise, Didier</creatorcontrib><creatorcontrib>Carella, Angelo Michele</creatorcontrib><creatorcontrib>Visani, Guiseppe</creatorcontrib><creatorcontrib>Savani, Bipin N.</creatorcontrib><creatorcontrib>Nagler, Arnon</creatorcontrib><creatorcontrib>Mohty, Mohamad</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>American journal of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dholaria, Bhagirathbhai</au><au>Labopin, Myriam</au><au>Angelucci, Emanuele</au><au>Ciceri, Fabio</au><au>Diez‐Martin, Jose L.</au><au>Bruno, Benedetto</au><au>Sica, Simona</au><au>Koc, Yener</au><au>Gülbas, Zafer</au><au>Schmid, Christoph</au><au>Blaise, Didier</au><au>Carella, Angelo Michele</au><au>Visani, Guiseppe</au><au>Savani, Bipin N.</au><au>Nagler, Arnon</au><au>Mohty, Mohamad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of total body irradiation‐ vs chemotherapy‐based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia</atitle><jtitle>American journal of hematology</jtitle><date>2020-10</date><risdate>2020</risdate><volume>95</volume><issue>10</issue><spage>1200</spage><epage>1208</epage><pages>1200-1208</pages><issn>0361-8609</issn><eissn>1096-8652</eissn><abstract>The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo‐HCT) is unknown. We studied the outcomes of total body irradiation (TBI) vs chemotherapy (CT) based MAC regimens in acute myeloid leukemia (AML) patients. The study included 1008 patients who underwent first haplo‐HCT with post‐transplant cyclophosphamide, following TBI (N = 89, 9%) or CT (n = 919, 91%) based MAC. Patients in the TBI cohort were younger (median age, 38 vs 47 years, P &lt; .01) and more likely to receive BM graft (57% vs 43%, P = .01). Two‐year overall chronic GVHD (cGVHD) incidence was 42% vs 27% (P &lt; .01) and extensive cGVHD incidence was 9% vs 12% (P = .33) in TBI and CT cohorts, respectively. Graft failure was reported in two (2%) TBI‐ and 65 (7%) CT‐MAC recipients (P = .08). Death from veno‐occlusive disease was reported in one (3%) TBI and 11 (3%) CT patients who died during the study period. In the multivariate analysis, TBI was associated with increased risk for overall cGVHD (hazard ratio = 1.95, 95% confidence interval:1.2‐3.1, P &lt; .01) compared to CT‐based MAC. The choice of conditioning regimen did not impact relapse incidence, leukemia‐free survival, non‐relapse mortality, overall survival or GVHD‐relapse‐free survival in multivariate analysis. In conclusion, major transplant outcomes were not statistically different between TBI‐based MAC and CT‐based MAC in patients with AML after haplo‐HCT/PTCy.</abstract><cop>Hoboken, USA</cop><pub>John Wiley &amp; Sons, Inc</pub><doi>10.1002/ajh.25934</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-2371-3655</orcidid><orcidid>https://orcid.org/0000-0002-6512-6080</orcidid><orcidid>https://orcid.org/0000-0002-0763-1265</orcidid><orcidid>https://orcid.org/0000-0001-8536-7781</orcidid><orcidid>https://orcid.org/0000-0002-7264-808X</orcidid><orcidid>https://orcid.org/0000-0001-7070-487X</orcidid><orcidid>https://orcid.org/0000-0003-4514-4748</orcidid><orcidid>https://orcid.org/0000-0003-0873-0123</orcidid><orcidid>https://orcid.org/0000-0002-3304-9965</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0361-8609
ispartof American journal of hematology, 2020-10, Vol.95 (10), p.1200-1208
issn 0361-8609
1096-8652
language eng
recordid cdi_hal_primary_oai_HAL_hal_03152832v1
source Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content
subjects Acute myeloid leukemia
Chemotherapy
Cyclophosphamide
Graft rejection
Graft-versus-host reaction
Grafts
Hematology
Immunology
Leukemia
Life Sciences
Multivariate analysis
Myeloid leukemia
Radiation
Stem cell transplantation
Transplantation
Transplants & implants
title Impact of total body irradiation‐ vs chemotherapy‐based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T20%3A12%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Impact%20of%20total%20body%20irradiation%E2%80%90%20vs%20chemotherapy%E2%80%90based%20myeloablative%20conditioning%20on%20outcomes%20of%20haploidentical%20hematopoietic%20cell%20transplantation%20for%20acute%20myelogenous%20leukemia&rft.jtitle=American%20journal%20of%20hematology&rft.au=Dholaria,%20Bhagirathbhai&rft.date=2020-10&rft.volume=95&rft.issue=10&rft.spage=1200&rft.epage=1208&rft.pages=1200-1208&rft.issn=0361-8609&rft.eissn=1096-8652&rft_id=info:doi/10.1002/ajh.25934&rft_dat=%3Cproquest_hal_p%3E2423515024%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2444009855&rft_id=info:pmid/&rfr_iscdi=true