Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure
We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML St...
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| Veröffentlicht in: | Leukemia 2017-06, Vol.31 (6), p.1306-1313 |
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| creator | Wattad, M Weber, D Döhner, K Krauter, J Gaidzik, V I Paschka, P Heuser, M Thol, F Kindler, T Lübbert, M Salih, H R Kündgen, A Horst, H-A Brossart, P Götze, K Nachbaur, D Köhne, C-H Ringhoffer, M Wulf, G Held, G Salwender, H Benner, A Ganser, A Döhner, H Schlenk, R F |
| description | We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML Study Group. After first induction therapy with idarubicin, cytarabine and etoposide (ICE), 845 patients had refractory disease. In addition, 180 patients, although responding to first induction, relapsed after second induction therapy. Of the 1025 patients with induction failure, 875 (median age 55 years) received intensive salvage therapy: 7+3-based (
n
=59), high-dose cytarabine combined with mitoxantrone (HAM;
n
=150), with all-
trans
retinoic acid (A; A-HAM) (
n
=247), with gemtuzumab ozogamicin and A (GO; GO-A-HAM) (
n
=140), other intensive regimens (
n
=165), experimental treatment (
n
=27) and direct allo-HCT (
n
=87). In patients receiving intensive salvage chemotherapy (
n
=761), response (complete remission/complete remission with incomplete hematological recovery (CR/CRi)) was associated with GO-A-HAM treatment (odds ratio (OR), 1.93;
P
=0.002), high-risk cytogenetics (OR, 0.62;
P
=0.006) and age (OR for a 10-year difference, 0.75;
P |
| doi_str_mv | 10.1038/leu.2017.23 |
| format | Article |
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n
=59), high-dose cytarabine combined with mitoxantrone (HAM;
n
=150), with all-
trans
retinoic acid (A; A-HAM) (
n
=247), with gemtuzumab ozogamicin and A (GO; GO-A-HAM) (
n
=140), other intensive regimens (
n
=165), experimental treatment (
n
=27) and direct allo-HCT (
n
=87). In patients receiving intensive salvage chemotherapy (
n
=761), response (complete remission/complete remission with incomplete hematological recovery (CR/CRi)) was associated with GO-A-HAM treatment (odds ratio (OR), 1.93;
P
=0.002), high-risk cytogenetics (OR, 0.62;
P
=0.006) and age (OR for a 10-year difference, 0.75;
P
<0.0001). Better survival probabilities were seen in an extended Cox regression model with time-dependent covariables in patients responding to salvage therapy (
P
<0.0001) and having the possibility to perform an allo-HCT (
P
<0.0001).
FLT3
internal tandem duplication, mutated
IDH1
and adverse cytogenetics were unfavorable factors for survival.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2017.23</identifier><identifier>PMID: 28138160</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/308 ; 692/308/2779/109 ; 692/4028/67/1059 ; 692/499 ; 692/699/67/1990/283/1897 ; 692/700/1750 ; Acute myelocytic leukemia ; Acute myeloid leukemia ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Blood tests ; Cancer ; Cancer Research ; Care and treatment ; Chemotherapy ; Clinical trials ; Combined Modality Therapy ; Critical Care Medicine ; Cytarabine ; Cytogenetics ; Dosage and administration ; Etoposide ; Failure ; Female ; Follow-Up Studies ; Gemtuzumab ozogamicin ; Hematology ; Hematopoietic stem cell transplantation ; Hematopoietic Stem Cell Transplantation - mortality ; Hematopoietic stem cells ; Hospitals ; Humans ; Induction therapy ; Intensive ; Internal Medicine ; Leukemia ; Leukemia, Myeloid, Acute - mortality ; Leukemia, Myeloid, Acute - pathology ; Leukemia, Myeloid, Acute - therapy ; Male ; Medical research ; Medicine ; Medicine & Public Health ; Methods ; Middle Aged ; Mitoxantrone ; Neoplasm Recurrence, Local - mortality ; Neoplasm Recurrence, Local - pathology ; Neoplasm Recurrence, Local - therapy ; Neoplasm Staging ; Oncology ; original-article ; Patient outcomes ; Patients ; Prognosis ; Prospective Studies ; Regression models ; Remission ; Remission (Medicine) ; Remission Induction ; Response rates ; Retinoic acid ; Salvage Therapy ; Survival ; Survival Rate ; Transplantation ; Transplantation, Homologous ; Transplants & implants ; Treatment outcome ; Young Adult</subject><ispartof>Leukemia, 2017-06, Vol.31 (6), p.1306-1313</ispartof><rights>Macmillan Publishers Limited, part of Springer Nature. 2017</rights><rights>COPYRIGHT 2017 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2017</rights><rights>Macmillan Publishers Limited, part of Springer Nature. 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c611t-e5f47181684608eaf951449d10581fe7757702cd2d65afe61ad1ac6761b79d9f3</citedby><cites>FETCH-LOGICAL-c611t-e5f47181684608eaf951449d10581fe7757702cd2d65afe61ad1ac6761b79d9f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2017.23$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2017.23$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28138160$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wattad, M</creatorcontrib><creatorcontrib>Weber, D</creatorcontrib><creatorcontrib>Döhner, K</creatorcontrib><creatorcontrib>Krauter, J</creatorcontrib><creatorcontrib>Gaidzik, V I</creatorcontrib><creatorcontrib>Paschka, P</creatorcontrib><creatorcontrib>Heuser, M</creatorcontrib><creatorcontrib>Thol, F</creatorcontrib><creatorcontrib>Kindler, T</creatorcontrib><creatorcontrib>Lübbert, M</creatorcontrib><creatorcontrib>Salih, H R</creatorcontrib><creatorcontrib>Kündgen, A</creatorcontrib><creatorcontrib>Horst, H-A</creatorcontrib><creatorcontrib>Brossart, P</creatorcontrib><creatorcontrib>Götze, K</creatorcontrib><creatorcontrib>Nachbaur, D</creatorcontrib><creatorcontrib>Köhne, C-H</creatorcontrib><creatorcontrib>Ringhoffer, M</creatorcontrib><creatorcontrib>Wulf, G</creatorcontrib><creatorcontrib>Held, G</creatorcontrib><creatorcontrib>Salwender, H</creatorcontrib><creatorcontrib>Benner, A</creatorcontrib><creatorcontrib>Ganser, A</creatorcontrib><creatorcontrib>Döhner, H</creatorcontrib><creatorcontrib>Schlenk, R F</creatorcontrib><creatorcontrib>for the German-Austrian AMLSG</creatorcontrib><title>Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML Study Group. After first induction therapy with idarubicin, cytarabine and etoposide (ICE), 845 patients had refractory disease. In addition, 180 patients, although responding to first induction, relapsed after second induction therapy. Of the 1025 patients with induction failure, 875 (median age 55 years) received intensive salvage therapy: 7+3-based (
n
=59), high-dose cytarabine combined with mitoxantrone (HAM;
n
=150), with all-
trans
retinoic acid (A; A-HAM) (
n
=247), with gemtuzumab ozogamicin and A (GO; GO-A-HAM) (
n
=140), other intensive regimens (
n
=165), experimental treatment (
n
=27) and direct allo-HCT (
n
=87). In patients receiving intensive salvage chemotherapy (
n
=761), response (complete remission/complete remission with incomplete hematological recovery (CR/CRi)) was associated with GO-A-HAM treatment (odds ratio (OR), 1.93;
P
=0.002), high-risk cytogenetics (OR, 0.62;
P
=0.006) and age (OR for a 10-year difference, 0.75;
P
<0.0001). Better survival probabilities were seen in an extended Cox regression model with time-dependent covariables in patients responding to salvage therapy (
P
<0.0001) and having the possibility to perform an allo-HCT (
P
<0.0001).
FLT3
internal tandem duplication, mutated
IDH1
and adverse cytogenetics were unfavorable factors for survival.</description><subject>692/308</subject><subject>692/308/2779/109</subject><subject>692/4028/67/1059</subject><subject>692/499</subject><subject>692/699/67/1990/283/1897</subject><subject>692/700/1750</subject><subject>Acute myelocytic leukemia</subject><subject>Acute myeloid leukemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Blood tests</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Combined Modality Therapy</subject><subject>Critical Care Medicine</subject><subject>Cytarabine</subject><subject>Cytogenetics</subject><subject>Dosage and administration</subject><subject>Etoposide</subject><subject>Failure</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gemtuzumab ozogamicin</subject><subject>Hematology</subject><subject>Hematopoietic stem cell transplantation</subject><subject>Hematopoietic Stem Cell Transplantation - mortality</subject><subject>Hematopoietic stem cells</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Induction therapy</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - mortality</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Leukemia, Myeloid, Acute - therapy</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methods</subject><subject>Middle Aged</subject><subject>Mitoxantrone</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplasm Recurrence, Local - therapy</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Regression models</subject><subject>Remission</subject><subject>Remission (Medicine)</subject><subject>Remission Induction</subject><subject>Response rates</subject><subject>Retinoic acid</subject><subject>Salvage Therapy</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Transplantation</subject><subject>Transplantation, Homologous</subject><subject>Transplants & implants</subject><subject>Treatment outcome</subject><subject>Young Adult</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkt9rFDEQxxdR7Fl98l0Cggh6Zya7-fVYij8KBV_0OaS7k7vU7OZMdq_0vzfLVblKOSUPCZnPfGeS-VbVS6AroLX6EHBaMQpyxepH1QIaKZacc3hcLahScik0a06qZzlfUzoHxdPqhCmoFQi6qMJFv7XtSKIj2YadXSNJuPY9DpnEoZzzNg4ZiR06EneYbAgkT2nndzYQPxDbTiOS_hZD9B0prfzA3lty48dNCXdTO_oi46wPU8Ln1RNnQ8YXd_tp9f3Tx2_nX5aXXz9fnJ9dLlsBMC6Ru0ZC6U81giq0TnNoGt0B5QocSsmlpKztWCe4dSjAdmBbIQVcSd1pV59Wb_e62xR_TphH0_vcYgh2wDhlAxpAgOYN_zeqRM0YrbUs6Ou_0Os4paE8xDABnNc18KMUaCoaRukhtbYBjR9cHJNt59LmTCjNFBc1P0o1uuGScQGFWj1AldWVUbRxQOfL_T3Z_0o4rPDmIGGDNoybHMM0zzbfVz4KHiq-24NtijkndGabfG_TrQFqZlebYiUzu9qwutCv7v50uuqx-8P-tnEB3u-BXELDGtPBpz-g9wtIn_sK</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Wattad, 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leukemia</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Blood tests</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Combined Modality Therapy</topic><topic>Critical Care Medicine</topic><topic>Cytarabine</topic><topic>Cytogenetics</topic><topic>Dosage and administration</topic><topic>Etoposide</topic><topic>Failure</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gemtuzumab ozogamicin</topic><topic>Hematology</topic><topic>Hematopoietic stem cell transplantation</topic><topic>Hematopoietic Stem Cell Transplantation - mortality</topic><topic>Hematopoietic stem cells</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Induction therapy</topic><topic>Intensive</topic><topic>Internal 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Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wattad, M</au><au>Weber, D</au><au>Döhner, K</au><au>Krauter, J</au><au>Gaidzik, V I</au><au>Paschka, P</au><au>Heuser, M</au><au>Thol, F</au><au>Kindler, T</au><au>Lübbert, M</au><au>Salih, H R</au><au>Kündgen, A</au><au>Horst, H-A</au><au>Brossart, P</au><au>Götze, K</au><au>Nachbaur, D</au><au>Köhne, C-H</au><au>Ringhoffer, M</au><au>Wulf, G</au><au>Held, G</au><au>Salwender, H</au><au>Benner, A</au><au>Ganser, A</au><au>Döhner, H</au><au>Schlenk, R F</au><aucorp>for the German-Austrian AMLSG</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>31</volume><issue>6</issue><spage>1306</spage><epage>1313</epage><pages>1306-1313</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML Study Group. After first induction therapy with idarubicin, cytarabine and etoposide (ICE), 845 patients had refractory disease. In addition, 180 patients, although responding to first induction, relapsed after second induction therapy. Of the 1025 patients with induction failure, 875 (median age 55 years) received intensive salvage therapy: 7+3-based (
n
=59), high-dose cytarabine combined with mitoxantrone (HAM;
n
=150), with all-
trans
retinoic acid (A; A-HAM) (
n
=247), with gemtuzumab ozogamicin and A (GO; GO-A-HAM) (
n
=140), other intensive regimens (
n
=165), experimental treatment (
n
=27) and direct allo-HCT (
n
=87). In patients receiving intensive salvage chemotherapy (
n
=761), response (complete remission/complete remission with incomplete hematological recovery (CR/CRi)) was associated with GO-A-HAM treatment (odds ratio (OR), 1.93;
P
=0.002), high-risk cytogenetics (OR, 0.62;
P
=0.006) and age (OR for a 10-year difference, 0.75;
P
<0.0001). Better survival probabilities were seen in an extended Cox regression model with time-dependent covariables in patients responding to salvage therapy (
P
<0.0001) and having the possibility to perform an allo-HCT (
P
<0.0001).
FLT3
internal tandem duplication, mutated
IDH1
and adverse cytogenetics were unfavorable factors for survival.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28138160</pmid><doi>10.1038/leu.2017.23</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2017-06, Vol.31 (6), p.1306-1313 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1911619545 |
| source | MEDLINE; Springer journals; Nature |
| subjects | 692/308 692/308/2779/109 692/4028/67/1059 692/499 692/699/67/1990/283/1897 692/700/1750 Acute myelocytic leukemia Acute myeloid leukemia Adolescent Adult Aged Aged, 80 and over Analysis Antineoplastic Combined Chemotherapy Protocols - therapeutic use Blood tests Cancer Cancer Research Care and treatment Chemotherapy Clinical trials Combined Modality Therapy Critical Care Medicine Cytarabine Cytogenetics Dosage and administration Etoposide Failure Female Follow-Up Studies Gemtuzumab ozogamicin Hematology Hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation - mortality Hematopoietic stem cells Hospitals Humans Induction therapy Intensive Internal Medicine Leukemia Leukemia, Myeloid, Acute - mortality Leukemia, Myeloid, Acute - pathology Leukemia, Myeloid, Acute - therapy Male Medical research Medicine Medicine & Public Health Methods Middle Aged Mitoxantrone Neoplasm Recurrence, Local - mortality Neoplasm Recurrence, Local - pathology Neoplasm Recurrence, Local - therapy Neoplasm Staging Oncology original-article Patient outcomes Patients Prognosis Prospective Studies Regression models Remission Remission (Medicine) Remission Induction Response rates Retinoic acid Salvage Therapy Survival Survival Rate Transplantation Transplantation, Homologous Transplants & implants Treatment outcome Young Adult |
| title | Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T16%3A55%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Impact%20of%20salvage%20regimens%20on%20response%20and%20overall%20survival%20in%20acute%20myeloid%20leukemia%20with%20induction%20failure&rft.jtitle=Leukemia&rft.au=Wattad,%20M&rft.aucorp=for%20the%20German-Austrian%20AMLSG&rft.date=2017-06-01&rft.volume=31&rft.issue=6&rft.spage=1306&rft.epage=1313&rft.pages=1306-1313&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/leu.2017.23&rft_dat=%3Cgale_proqu%3EA494572561%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1906420057&rft_id=info:pmid/28138160&rft_galeid=A494572561&rfr_iscdi=true |