Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma
Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence in...
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| Veröffentlicht in: | Leukemia 2016-03, Vol.30 (3), p.633-639 |
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| creator | Kaufman, G P Gertz, M A Dispenzieri, A Lacy, M Q Buadi, F K Dingli, D Hayman, S R Kapoor, P Lust, J A Russell, S Go, R S Hwa, Y L Kyle, R A Rajkumar, S V Kumar, S K |
| description | Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence
in situ
hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years. |
| doi_str_mv | 10.1038/leu.2015.287 |
| format | Article |
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in situ
hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2015.287</identifier><identifier>PMID: 26487275</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/32 ; 631/1647/2017/1947 ; 631/208/2489/1381/1853 ; 692/499 ; 692/699/67/1059 ; 692/699/67/1059/99 ; 692/699/67/1990/804 ; Abnormalities ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Autografts ; Bortezomib ; Bortezomib - therapeutic use ; Cancer Research ; Chromosome 14 ; Chromosome translocations ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 17 ; Classification ; Critical Care Medicine ; Cytogenetic Analysis ; Cytogenetics ; Dexamethasone - therapeutic use ; Diagnosis ; Dose-response relationship (Biochemistry) ; Drug therapy ; Fluorescence ; Fluorescence in situ hybridization ; Hematology ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; Induction Chemotherapy - methods ; Intensive ; Internal Medicine ; Maintenance ; Male ; Markers ; Medicine ; Medicine & Public Health ; Melphalan ; Melphalan - therapeutic use ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - diagnosis ; Multiple Myeloma - genetics ; Multiple Myeloma - mortality ; Multiple Myeloma - therapy ; Observations ; Oncology ; original-article ; Patient outcomes ; Prognosis ; Remission Induction ; Retrospective Studies ; Risk ; Stem cell transplantation ; Stem cells ; Survival Analysis ; Thalidomide - analogs & derivatives ; Thalidomide - therapeutic use ; Therapy ; Translocation, Genetic ; Transplantation ; Transplantation, Autologous ; Transplants & implants ; Treatment Outcome</subject><ispartof>Leukemia, 2016-03, Vol.30 (3), p.633-639</ispartof><rights>Macmillan Publishers Limited 2016</rights><rights>COPYRIGHT 2016 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2016</rights><rights>Macmillan Publishers Limited 2016.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c652t-31d9119da6eec3648cfbb25e6a5d3b1799cd3699cbab7411fb5df9d22de4f2d23</citedby><cites>FETCH-LOGICAL-c652t-31d9119da6eec3648cfbb25e6a5d3b1799cd3699cbab7411fb5df9d22de4f2d23</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.2015.287$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2015.287$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26487275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaufman, G P</creatorcontrib><creatorcontrib>Gertz, M A</creatorcontrib><creatorcontrib>Dispenzieri, A</creatorcontrib><creatorcontrib>Lacy, M Q</creatorcontrib><creatorcontrib>Buadi, F K</creatorcontrib><creatorcontrib>Dingli, D</creatorcontrib><creatorcontrib>Hayman, S R</creatorcontrib><creatorcontrib>Kapoor, P</creatorcontrib><creatorcontrib>Lust, J A</creatorcontrib><creatorcontrib>Russell, S</creatorcontrib><creatorcontrib>Go, R S</creatorcontrib><creatorcontrib>Hwa, Y L</creatorcontrib><creatorcontrib>Kyle, R A</creatorcontrib><creatorcontrib>Rajkumar, S V</creatorcontrib><creatorcontrib>Kumar, S K</creatorcontrib><title>Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence
in situ
hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years.</description><subject>14/32</subject><subject>631/1647/2017/1947</subject><subject>631/208/2489/1381/1853</subject><subject>692/499</subject><subject>692/699/67/1059</subject><subject>692/699/67/1059/99</subject><subject>692/699/67/1990/804</subject><subject>Abnormalities</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Autografts</subject><subject>Bortezomib</subject><subject>Bortezomib - therapeutic use</subject><subject>Cancer Research</subject><subject>Chromosome 14</subject><subject>Chromosome translocations</subject><subject>Chromosomes, Human, Pair 11</subject><subject>Chromosomes, Human, Pair 14</subject><subject>Chromosomes, Human, Pair 17</subject><subject>Classification</subject><subject>Critical Care Medicine</subject><subject>Cytogenetic Analysis</subject><subject>Cytogenetics</subject><subject>Dexamethasone - therapeutic use</subject><subject>Diagnosis</subject><subject>Dose-response relationship (Biochemistry)</subject><subject>Drug therapy</subject><subject>Fluorescence</subject><subject>Fluorescence in situ hybridization</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Induction Chemotherapy - methods</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Maintenance</subject><subject>Male</subject><subject>Markers</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Melphalan</subject><subject>Melphalan - therapeutic use</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - diagnosis</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - mortality</subject><subject>Multiple Myeloma - therapy</subject><subject>Observations</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patient outcomes</subject><subject>Prognosis</subject><subject>Remission Induction</subject><subject>Retrospective Studies</subject><subject>Risk</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Survival Analysis</subject><subject>Thalidomide - analogs & derivatives</subject><subject>Thalidomide - therapeutic use</subject><subject>Therapy</subject><subject>Translocation, Genetic</subject><subject>Transplantation</subject><subject>Transplantation, Autologous</subject><subject>Transplants & implants</subject><subject>Treatment Outcome</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNks-L1TAQx4so7nP15lkCgniwzyZtkva4LP5YWPCi55AmkzZL2tQkRfrfm_JW3ZVFJGEGMp-ZZDLfoniJqyOu6va9g_VIKkyPpOWPigNuOCsppfhxcajalpesI81Z8SzGm6rag-xpcUZY03LC6aEwV9MiVULeILUlP8AMySqknIzRGqtksn5G-16T8hNEZLxz_oedBwQyuA2NdhhL7SOgNEKQy4bsjKbVJbs4QNMGzk_yefHESBfhxa0_L759_PD18nN5_eXT1eXFdakYJamsse4w7rRkAKrOj1Sm7wkFJqmue8y7TumaZdvLnjcYm55q02lCNDSGaFKfF29PdZfgv68Qk5hsVOCcnMGvUWDO67ZmnNP_QSuSDWsz-vov9MavYc6NiPyTlDeUEfYvCnPWsYoT3P2hBulA2Nn4FKTarxYXTR5PzXGNM3V8gMpLw2SVn8HYfH4v4c2dhBGkS2P0bt3HF--D706gCj7GAEYswU4ybAJXYheUyIISu6BEFlTGX902tfYT6N_wLwVloDwBMYfmAcKdrh8q-BO3VtNI</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>Kaufman, G P</creator><creator>Gertz, M A</creator><creator>Dispenzieri, A</creator><creator>Lacy, M Q</creator><creator>Buadi, F K</creator><creator>Dingli, D</creator><creator>Hayman, S R</creator><creator>Kapoor, P</creator><creator>Lust, J A</creator><creator>Russell, S</creator><creator>Go, R S</creator><creator>Hwa, Y L</creator><creator>Kyle, R A</creator><creator>Rajkumar, S V</creator><creator>Kumar, S K</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20160301</creationdate><title>Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma</title><author>Kaufman, G P ; Gertz, M A ; Dispenzieri, A ; Lacy, M Q ; Buadi, F K ; Dingli, D ; Hayman, S R ; Kapoor, P ; Lust, J A ; Russell, S ; Go, R S ; Hwa, Y L ; Kyle, R A ; Rajkumar, S V ; Kumar, S K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c652t-31d9119da6eec3648cfbb25e6a5d3b1799cd3699cbab7411fb5df9d22de4f2d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>14/32</topic><topic>631/1647/2017/1947</topic><topic>631/208/2489/1381/1853</topic><topic>692/499</topic><topic>692/699/67/1059</topic><topic>692/699/67/1059/99</topic><topic>692/699/67/1990/804</topic><topic>Abnormalities</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Autografts</topic><topic>Bortezomib</topic><topic>Bortezomib - therapeutic use</topic><topic>Cancer Research</topic><topic>Chromosome 14</topic><topic>Chromosome translocations</topic><topic>Chromosomes, Human, Pair 11</topic><topic>Chromosomes, Human, Pair 14</topic><topic>Chromosomes, Human, Pair 17</topic><topic>Classification</topic><topic>Critical Care Medicine</topic><topic>Cytogenetic Analysis</topic><topic>Cytogenetics</topic><topic>Dexamethasone - therapeutic use</topic><topic>Diagnosis</topic><topic>Dose-response relationship (Biochemistry)</topic><topic>Drug therapy</topic><topic>Fluorescence</topic><topic>Fluorescence in situ hybridization</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Induction Chemotherapy - methods</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Maintenance</topic><topic>Male</topic><topic>Markers</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Melphalan</topic><topic>Melphalan - 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Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaufman, G P</au><au>Gertz, M A</au><au>Dispenzieri, A</au><au>Lacy, M Q</au><au>Buadi, F K</au><au>Dingli, D</au><au>Hayman, S R</au><au>Kapoor, P</au><au>Lust, J A</au><au>Russell, S</au><au>Go, R S</au><au>Hwa, Y L</au><au>Kyle, R A</au><au>Rajkumar, S V</au><au>Kumar, S K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>30</volume><issue>3</issue><spage>633</spage><epage>639</epage><pages>633-639</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence
in situ
hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26487275</pmid><doi>10.1038/leu.2015.287</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2016-03, Vol.30 (3), p.633-639 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1773836775 |
| source | MEDLINE; SpringerLink Journals; Nature |
| subjects | 14/32 631/1647/2017/1947 631/208/2489/1381/1853 692/499 692/699/67/1059 692/699/67/1059/99 692/699/67/1990/804 Abnormalities Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Autografts Bortezomib Bortezomib - therapeutic use Cancer Research Chromosome 14 Chromosome translocations Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 14 Chromosomes, Human, Pair 17 Classification Critical Care Medicine Cytogenetic Analysis Cytogenetics Dexamethasone - therapeutic use Diagnosis Dose-response relationship (Biochemistry) Drug therapy Fluorescence Fluorescence in situ hybridization Hematology Hematopoietic Stem Cell Transplantation Humans In Situ Hybridization, Fluorescence Induction Chemotherapy - methods Intensive Internal Medicine Maintenance Male Markers Medicine Medicine & Public Health Melphalan Melphalan - therapeutic use Middle Aged Multiple myeloma Multiple Myeloma - diagnosis Multiple Myeloma - genetics Multiple Myeloma - mortality Multiple Myeloma - therapy Observations Oncology original-article Patient outcomes Prognosis Remission Induction Retrospective Studies Risk Stem cell transplantation Stem cells Survival Analysis Thalidomide - analogs & derivatives Thalidomide - therapeutic use Therapy Translocation, Genetic Transplantation Transplantation, Autologous Transplants & implants Treatment Outcome |
| title | Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T03%3A32%3A21IST&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%20cytogenetic%20classification%20on%20outcomes%20following%20early%20high-dose%20therapy%20in%20multiple%20myeloma&rft.jtitle=Leukemia&rft.au=Kaufman,%20G%20P&rft.date=2016-03-01&rft.volume=30&rft.issue=3&rft.spage=633&rft.epage=639&rft.pages=633-639&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/leu.2015.287&rft_dat=%3Cgale_proqu%3EA447637131%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=1769607219&rft_id=info:pmid/26487275&rft_galeid=A447637131&rfr_iscdi=true |