Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients
Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: ‘favorable’ and ‘unfavorable’. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 consecutive patients, we performed stepwise analysis of impact on survival from in...
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| Veröffentlicht in: | Leukemia 2018-05, Vol.32 (5), p.1189-1199 |
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| creator | Tefferi, Ayalew Nicolosi, Maura Mudireddy, Mythri Lasho, Terra L. Gangat, Naseema Begna, Kebede H. Hanson, Curtis A. Ketterling, Rhett P. Pardanani, Animesh |
| description | Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: ‘favorable’ and ‘unfavorable’. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 consecutive patients, we performed stepwise analysis of impact on survival from individual and prognostically ordered cytogenetic abnormalities, leading to a revised three-tiered risk model: ‘very high risk (VHR)’—single/multiple abnormalities of −7, i(17q), inv(3)/3q21, 12p−/12p11.2, 11q−/11q23, or other autosomal trisomies not including + 8/ + 9 (e.g., +21, +19); ‘favorable’—normal karyotype or sole abnormalities of 13q−, +9, 20q−, chromosome 1 translocation/duplication or sex chromosome abnormality including -Y; ‘unfavorable’—all other abnormalities. Median survivals for VHR (
n
= 75), unfavorable (
n
= 190) and favorable (
n
= 737) risk categories were 1.2 (HR 3.8, 95% CI 2.9–4.9), 2.9 (HR 1.7, 95% CI 1.4–2.0) and 4.4 years and survival impact was independent of clinically derived prognostic systems, driver and
ASXL1
/
SRSF2
mutations. The revised model was also effective in predicting leukemic transformation: HRs (95% CI) were 4.4 (2.0–9.4) for VHR and 2.0 (1.2–3.4) for unfavorable. The impact of driver mutations on survival was confined to favorable and that of
ASXL1
/
SRSF2
mutations to favorable/unfavorable cytogenetic risk categories. The current study clarifies the prognostic hierarchy of genetic risk factors in PMF and provides a more refined three-tiered cytogenetic risk model. |
| doi_str_mv | 10.1038/s41375-018-0018-z |
| format | Article |
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n
= 75), unfavorable (
n
= 190) and favorable (
n
= 737) risk categories were 1.2 (HR 3.8, 95% CI 2.9–4.9), 2.9 (HR 1.7, 95% CI 1.4–2.0) and 4.4 years and survival impact was independent of clinically derived prognostic systems, driver and
ASXL1
/
SRSF2
mutations. The revised model was also effective in predicting leukemic transformation: HRs (95% CI) were 4.4 (2.0–9.4) for VHR and 2.0 (1.2–3.4) for unfavorable. The impact of driver mutations on survival was confined to favorable and that of
ASXL1
/
SRSF2
mutations to favorable/unfavorable cytogenetic risk categories. The current study clarifies the prognostic hierarchy of genetic risk factors in PMF and provides a more refined three-tiered cytogenetic risk model.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-018-0018-z</identifier><identifier>PMID: 29472717</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1990/2331 ; 692/699/1541/1990/2331 ; Abnormalities ; Adult ; Aged ; Aged, 80 and over ; Cancer Research ; Cell Transformation, Neoplastic - genetics ; Chromosomes ; Critical Care Medicine ; Cytogenetics - methods ; Female ; Hematology ; Humans ; Impact analysis ; Intensive ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Mutation ; Oncology ; Patient Generated Health Data ; Primary Myelofibrosis - diagnosis ; Primary Myelofibrosis - genetics ; Primary Myelofibrosis - mortality ; Prognosis ; Risk analysis ; Risk Assessment - methods ; Survival ; Survival Analysis ; System effectiveness ; Young Adult</subject><ispartof>Leukemia, 2018-05, Vol.32 (5), p.1189-1199</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by-nc-nd/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-c536t-d8d415208336448544d7590f128f892c781c3d73d2cb6a886e97bd8665ced2013</citedby><cites>FETCH-LOGICAL-c536t-d8d415208336448544d7590f128f892c781c3d73d2cb6a886e97bd8665ced2013</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/s41375-018-0018-z$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-018-0018-z$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29472717$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tefferi, Ayalew</creatorcontrib><creatorcontrib>Nicolosi, Maura</creatorcontrib><creatorcontrib>Mudireddy, Mythri</creatorcontrib><creatorcontrib>Lasho, Terra L.</creatorcontrib><creatorcontrib>Gangat, Naseema</creatorcontrib><creatorcontrib>Begna, Kebede H.</creatorcontrib><creatorcontrib>Hanson, Curtis A.</creatorcontrib><creatorcontrib>Ketterling, Rhett P.</creatorcontrib><creatorcontrib>Pardanani, Animesh</creatorcontrib><title>Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: ‘favorable’ and ‘unfavorable’. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 consecutive patients, we performed stepwise analysis of impact on survival from individual and prognostically ordered cytogenetic abnormalities, leading to a revised three-tiered risk model: ‘very high risk (VHR)’—single/multiple abnormalities of −7, i(17q), inv(3)/3q21, 12p−/12p11.2, 11q−/11q23, or other autosomal trisomies not including + 8/ + 9 (e.g., +21, +19); ‘favorable’—normal karyotype or sole abnormalities of 13q−, +9, 20q−, chromosome 1 translocation/duplication or sex chromosome abnormality including -Y; ‘unfavorable’—all other abnormalities. Median survivals for VHR (
n
= 75), unfavorable (
n
= 190) and favorable (
n
= 737) risk categories were 1.2 (HR 3.8, 95% CI 2.9–4.9), 2.9 (HR 1.7, 95% CI 1.4–2.0) and 4.4 years and survival impact was independent of clinically derived prognostic systems, driver and
ASXL1
/
SRSF2
mutations. The revised model was also effective in predicting leukemic transformation: HRs (95% CI) were 4.4 (2.0–9.4) for VHR and 2.0 (1.2–3.4) for unfavorable. The impact of driver mutations on survival was confined to favorable and that of
ASXL1
/
SRSF2
mutations to favorable/unfavorable cytogenetic risk categories. The current study clarifies the prognostic hierarchy of genetic risk factors in PMF and provides a more refined three-tiered cytogenetic risk model.</description><subject>631/67/1990/2331</subject><subject>692/699/1541/1990/2331</subject><subject>Abnormalities</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cancer Research</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Chromosomes</subject><subject>Critical Care Medicine</subject><subject>Cytogenetics - methods</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Impact analysis</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Oncology</subject><subject>Patient Generated Health Data</subject><subject>Primary Myelofibrosis - diagnosis</subject><subject>Primary Myelofibrosis - genetics</subject><subject>Primary Myelofibrosis - mortality</subject><subject>Prognosis</subject><subject>Risk analysis</subject><subject>Risk Assessment - methods</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>System effectiveness</subject><subject>Young Adult</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kV1LHDEUhkOp6Nb6A7yRQG96MzXJ5Gt6URBptSAIYq9DJsmssTOTbTK7sP56z7Bbawu9yQmc57zn40XolJJPlNT6vHBaK1ERqisyP09v0IJyJSshBH2LFkRrVcmG8SP0rpRHYCApD9ERa7hiiqoFGu7CJpbgsdtOaRnGMEWHcyw_cZmynWIXHbxpxHHEqxwHm7d42IY-dbHNqcTyGdvR9lv44dbOQsBSQhgUdCkPULwJeAUhjFN5jw4625dwso_H6Me3r_eX19XN7dX3y4ubyolaTpXXnlPBiK5rybkWnHslGtJRpjvdMKc0dbVXtWeulVZrGRrVei2lcMEzQutj9GWnu1q3Q_AOemfbm_0CJtlo_s6M8cEs08aIhhMpOAh83Avk9GsdymSGWFzoezuGtC6GEaIazZlUgH74B31M6ww3mSmYX0g4O1B0Rzm4WsmhexmGEjObaXZmGvDRzGaaJ6g5e73FS8Vv9wBgO6BAalyG_Kf1_1WfAUperC0</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>Tefferi, Ayalew</creator><creator>Nicolosi, Maura</creator><creator>Mudireddy, Mythri</creator><creator>Lasho, Terra L.</creator><creator>Gangat, Naseema</creator><creator>Begna, Kebede H.</creator><creator>Hanson, Curtis A.</creator><creator>Ketterling, Rhett P.</creator><creator>Pardanani, Animesh</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>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><scope>5PM</scope></search><sort><creationdate>20180501</creationdate><title>Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients</title><author>Tefferi, Ayalew ; Nicolosi, Maura ; Mudireddy, Mythri ; Lasho, Terra L. ; Gangat, Naseema ; Begna, Kebede H. ; Hanson, Curtis A. ; Ketterling, Rhett P. ; Pardanani, Animesh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-d8d415208336448544d7590f128f892c781c3d73d2cb6a886e97bd8665ced2013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>631/67/1990/2331</topic><topic>692/699/1541/1990/2331</topic><topic>Abnormalities</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cancer Research</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Chromosomes</topic><topic>Critical Care Medicine</topic><topic>Cytogenetics - methods</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Impact analysis</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Oncology</topic><topic>Patient Generated Health Data</topic><topic>Primary Myelofibrosis - diagnosis</topic><topic>Primary Myelofibrosis - genetics</topic><topic>Primary Myelofibrosis - mortality</topic><topic>Prognosis</topic><topic>Risk analysis</topic><topic>Risk Assessment - methods</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>System effectiveness</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tefferi, Ayalew</creatorcontrib><creatorcontrib>Nicolosi, Maura</creatorcontrib><creatorcontrib>Mudireddy, Mythri</creatorcontrib><creatorcontrib>Lasho, Terra L.</creatorcontrib><creatorcontrib>Gangat, Naseema</creatorcontrib><creatorcontrib>Begna, Kebede H.</creatorcontrib><creatorcontrib>Hanson, Curtis A.</creatorcontrib><creatorcontrib>Ketterling, Rhett P.</creatorcontrib><creatorcontrib>Pardanani, Animesh</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids 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>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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Medical Database</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tefferi, Ayalew</au><au>Nicolosi, Maura</au><au>Mudireddy, Mythri</au><au>Lasho, Terra L.</au><au>Gangat, Naseema</au><au>Begna, Kebede H.</au><au>Hanson, Curtis A.</au><au>Ketterling, Rhett P.</au><au>Pardanani, Animesh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>32</volume><issue>5</issue><spage>1189</spage><epage>1199</epage><pages>1189-1199</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: ‘favorable’ and ‘unfavorable’. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 consecutive patients, we performed stepwise analysis of impact on survival from individual and prognostically ordered cytogenetic abnormalities, leading to a revised three-tiered risk model: ‘very high risk (VHR)’—single/multiple abnormalities of −7, i(17q), inv(3)/3q21, 12p−/12p11.2, 11q−/11q23, or other autosomal trisomies not including + 8/ + 9 (e.g., +21, +19); ‘favorable’—normal karyotype or sole abnormalities of 13q−, +9, 20q−, chromosome 1 translocation/duplication or sex chromosome abnormality including -Y; ‘unfavorable’—all other abnormalities. Median survivals for VHR (
n
= 75), unfavorable (
n
= 190) and favorable (
n
= 737) risk categories were 1.2 (HR 3.8, 95% CI 2.9–4.9), 2.9 (HR 1.7, 95% CI 1.4–2.0) and 4.4 years and survival impact was independent of clinically derived prognostic systems, driver and
ASXL1
/
SRSF2
mutations. The revised model was also effective in predicting leukemic transformation: HRs (95% CI) were 4.4 (2.0–9.4) for VHR and 2.0 (1.2–3.4) for unfavorable. The impact of driver mutations on survival was confined to favorable and that of
ASXL1
/
SRSF2
mutations to favorable/unfavorable cytogenetic risk categories. The current study clarifies the prognostic hierarchy of genetic risk factors in PMF and provides a more refined three-tiered cytogenetic risk model.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29472717</pmid><doi>10.1038/s41375-018-0018-z</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Leukemia, 2018-05, Vol.32 (5), p.1189-1199 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | 631/67/1990/2331 692/699/1541/1990/2331 Abnormalities Adult Aged Aged, 80 and over Cancer Research Cell Transformation, Neoplastic - genetics Chromosomes Critical Care Medicine Cytogenetics - methods Female Hematology Humans Impact analysis Intensive Internal Medicine Male Medicine Medicine & Public Health Middle Aged Mutation Oncology Patient Generated Health Data Primary Myelofibrosis - diagnosis Primary Myelofibrosis - genetics Primary Myelofibrosis - mortality Prognosis Risk analysis Risk Assessment - methods Survival Survival Analysis System effectiveness Young Adult |
| title | Revised cytogenetic risk stratification in primary myelofibrosis: analysis based on 1002 informative patients |
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