Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004
We conducted a cytogenetic analysis of 642 children with de novo acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK + ), complex (CK + ) and hypodiploid (HK + ) karyo...
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| creator | Rasche, M von Neuhoff, C Dworzak, M Bourquin, J-P Bradtke, J Göhring, G Escherich, G Fleischhack, G Graf, N Gruhn, B Haas, O A Klingebiel, T Kremens, B Lehrnbecher, T von Stackelberg, A Tchinda, J Zemanova, Z Thiede, C von Neuhoff, N Zimmermann, M Creutzig, U Reinhardt, D |
| description | We conducted a cytogenetic analysis of 642 children with
de novo
acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK
+
), complex (CK
+
) and hypodiploid (HK
+
) karyotypes, individually and in combination. Multivariate regression analysis identified in particular MK
+
(
n
=22) as a new independent risk factor for poor event-free survival (EFS 23±9% vs 53±2% for all other patients,
P
=0.0003), even after exclusion of four patients with monosomy 7 (EFS 28±11%,
P
=0.0081). CK
+
patients without MK had a better prognosis (
n
=47, EFS 47±8%,
P
=0.46) than those with MK
+
(
n
=12, EFS 25±13%,
P
=0.024). HK
+
(
n
=37, EFS 44±8% for total cohort,
P
=0.3) influenced outcome only when t(8;21) patients were excluded (remaining
n
=16, EFS 9±8%,
P |
| doi_str_mv | 10.1038/leu.2017.121 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5729330</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A517561433</galeid><sourcerecordid>A517561433</sourcerecordid><originalsourceid>FETCH-LOGICAL-c548t-7e93c5e00d9cfa4a1450d19fa763394b92543397e2aca3afa700df2ba957d06e3</originalsourceid><addsrcrecordid>eNptkt2L1DAUxYMo7jj65rMEBPHBjvlsGx-EcXFXYRZf9Dlk0tuZrG1Sk1bY_950Z11nZCmk4d7fOe1NDkIvKVlRwuv3HUwrRmi1oow-QgsqqrKQUtLHaEHquipKxcQZepbSNSFzs3yKzlgtBC9JuUDuEnwYbwYowjTa0AO2IUbozOiCT9h5PEDjzBidxeurzQc87gG7fjB2xKHFBvfBhxR60-GfJt7cWs2qLMilrCg-XVxhRoh4jp60pkvw4u69RD8uPn8__1Jsvl1-PV9vCitFPRYVKG4lENIo2xphqJCkoao1Vcm5ElvFpMibCpixhptcz2jLtkbJqiEl8CX6ePAdpm0PjQU_RtPpIbo-_6AOxunTjnd7vQu_tayY4pxkg7d3BjH8miCNunfJQtcZD2FKmtaKzVxeluj1f-h1mKLP42mqKk4oUTX7R-1MB9r5NuTv2tlUryWtZEnzRJlaPUDlp4He2eChdbl-InhzJNiD6cZ9Ct10e3On4LsDaGNIKUJ7fxiU6DlDOmdIzxnSOUMZf3V8gPfw39BkoDgAKbf8DuLR1A8Z_gHDw842</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1973010982</pqid></control><display><type>article</type><title>Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Nature Journals Online</source><creator>Rasche, M ; von Neuhoff, C ; Dworzak, M ; Bourquin, J-P ; Bradtke, J ; Göhring, G ; Escherich, G ; Fleischhack, G ; Graf, N ; Gruhn, B ; Haas, O A ; Klingebiel, T ; Kremens, B ; Lehrnbecher, T ; von Stackelberg, A ; Tchinda, J ; Zemanova, Z ; Thiede, C ; von Neuhoff, N ; Zimmermann, M ; Creutzig, U ; Reinhardt, D</creator><creatorcontrib>Rasche, M ; von Neuhoff, C ; Dworzak, M ; Bourquin, J-P ; Bradtke, J ; Göhring, G ; Escherich, G ; Fleischhack, G ; Graf, N ; Gruhn, B ; Haas, O A ; Klingebiel, T ; Kremens, B ; Lehrnbecher, T ; von Stackelberg, A ; Tchinda, J ; Zemanova, Z ; Thiede, C ; von Neuhoff, N ; Zimmermann, M ; Creutzig, U ; Reinhardt, D</creatorcontrib><description>We conducted a cytogenetic analysis of 642 children with
de novo
acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK
+
), complex (CK
+
) and hypodiploid (HK
+
) karyotypes, individually and in combination. Multivariate regression analysis identified in particular MK
+
(
n
=22) as a new independent risk factor for poor event-free survival (EFS 23±9% vs 53±2% for all other patients,
P
=0.0003), even after exclusion of four patients with monosomy 7 (EFS 28±11%,
P
=0.0081). CK
+
patients without MK had a better prognosis (
n
=47, EFS 47±8%,
P
=0.46) than those with MK
+
(
n
=12, EFS 25±13%,
P
=0.024). HK
+
(
n
=37, EFS 44±8% for total cohort,
P
=0.3) influenced outcome only when t(8;21) patients were excluded (remaining
n
=16, EFS 9±8%,
P
<0.0001). An extremely poor outcome was observed for MK
+
/HK
+
patients (
n
=10, EFS 10±10%,
P
<0.0001). Finally, isolated trisomy 8 was also associated with low EFS (
n
=16, EFS 25±11%,
P
=0.0091). In conclusion, monosomal karyotype is a strong and independent predictor for high-risk pediatric AML. In addition, isolated trisomy 8 and hypodiploidy without t(8;21) coincide with dismal outcome. These results have important implications for risk stratification and should be further validated in independent pediatric cohorts.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2017.121</identifier><identifier>PMID: 28443606</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/32 ; 631/208/1405 ; 631/67/68 ; 692/308/2056 ; 692/4028/67/2332 ; 692/53/2422 ; 692/699/67 ; 692/699/67/1990/283/1897 ; Aberration ; Acute myelocytic leukemia ; Acute myeloid leukemia ; Cancer Research ; Care and treatment ; Children ; Chromosome Aberrations ; Chromosomes, Human, Pair 7 ; Clinical Trials as Topic ; Critical Care Medicine ; Diagnosis ; Female ; Genetic Variation ; Genotype ; Hematology ; Humans ; Hypodiploidy ; Intensive ; Internal Medicine ; Karyotype ; Karyotypes ; Karyotyping ; Leukemia ; Leukemia, Myeloid, Acute - diagnosis ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - mortality ; Male ; Medical prognosis ; Medicine ; Medicine & Public Health ; Monosomy ; Mutation ; Myeloid leukemia ; Oncology ; Original ; original-article ; Patients ; Pediatrics ; Polymerase chain reaction ; Prognosis ; Regression analysis ; Risk factors ; Stem cell transplantation ; Survival Analysis ; Trisomy</subject><ispartof>Leukemia, 2017-12, Vol.31 (12), p.2807-2814</ispartof><rights>The Author(s) 2017</rights><rights>COPYRIGHT 2017 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2017</rights><rights>Copyright © 2017 The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c548t-7e93c5e00d9cfa4a1450d19fa763394b92543397e2aca3afa700df2ba957d06e3</citedby><cites>FETCH-LOGICAL-c548t-7e93c5e00d9cfa4a1450d19fa763394b92543397e2aca3afa700df2ba957d06e3</cites><orcidid>0000-0002-2248-323X</orcidid></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.2017.121$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2017.121$$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/28443606$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rasche, M</creatorcontrib><creatorcontrib>von Neuhoff, C</creatorcontrib><creatorcontrib>Dworzak, M</creatorcontrib><creatorcontrib>Bourquin, J-P</creatorcontrib><creatorcontrib>Bradtke, J</creatorcontrib><creatorcontrib>Göhring, G</creatorcontrib><creatorcontrib>Escherich, G</creatorcontrib><creatorcontrib>Fleischhack, G</creatorcontrib><creatorcontrib>Graf, N</creatorcontrib><creatorcontrib>Gruhn, B</creatorcontrib><creatorcontrib>Haas, O A</creatorcontrib><creatorcontrib>Klingebiel, T</creatorcontrib><creatorcontrib>Kremens, B</creatorcontrib><creatorcontrib>Lehrnbecher, T</creatorcontrib><creatorcontrib>von Stackelberg, A</creatorcontrib><creatorcontrib>Tchinda, J</creatorcontrib><creatorcontrib>Zemanova, Z</creatorcontrib><creatorcontrib>Thiede, C</creatorcontrib><creatorcontrib>von Neuhoff, N</creatorcontrib><creatorcontrib>Zimmermann, M</creatorcontrib><creatorcontrib>Creutzig, U</creatorcontrib><creatorcontrib>Reinhardt, D</creatorcontrib><title>Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>We conducted a cytogenetic analysis of 642 children with
de novo
acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK
+
), complex (CK
+
) and hypodiploid (HK
+
) karyotypes, individually and in combination. Multivariate regression analysis identified in particular MK
+
(
n
=22) as a new independent risk factor for poor event-free survival (EFS 23±9% vs 53±2% for all other patients,
P
=0.0003), even after exclusion of four patients with monosomy 7 (EFS 28±11%,
P
=0.0081). CK
+
patients without MK had a better prognosis (
n
=47, EFS 47±8%,
P
=0.46) than those with MK
+
(
n
=12, EFS 25±13%,
P
=0.024). HK
+
(
n
=37, EFS 44±8% for total cohort,
P
=0.3) influenced outcome only when t(8;21) patients were excluded (remaining
n
=16, EFS 9±8%,
P
<0.0001). An extremely poor outcome was observed for MK
+
/HK
+
patients (
n
=10, EFS 10±10%,
P
<0.0001). Finally, isolated trisomy 8 was also associated with low EFS (
n
=16, EFS 25±11%,
P
=0.0091). In conclusion, monosomal karyotype is a strong and independent predictor for high-risk pediatric AML. In addition, isolated trisomy 8 and hypodiploidy without t(8;21) coincide with dismal outcome. These results have important implications for risk stratification and should be further validated in independent pediatric cohorts.</description><subject>14/32</subject><subject>631/208/1405</subject><subject>631/67/68</subject><subject>692/308/2056</subject><subject>692/4028/67/2332</subject><subject>692/53/2422</subject><subject>692/699/67</subject><subject>692/699/67/1990/283/1897</subject><subject>Aberration</subject><subject>Acute myelocytic leukemia</subject><subject>Acute myeloid leukemia</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Children</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes, Human, Pair 7</subject><subject>Clinical Trials as Topic</subject><subject>Critical Care Medicine</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Genetic Variation</subject><subject>Genotype</subject><subject>Hematology</subject><subject>Humans</subject><subject>Hypodiploidy</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Karyotype</subject><subject>Karyotypes</subject><subject>Karyotyping</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - diagnosis</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - mortality</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Monosomy</subject><subject>Mutation</subject><subject>Myeloid leukemia</subject><subject>Oncology</subject><subject>Original</subject><subject>original-article</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Regression analysis</subject><subject>Risk factors</subject><subject>Stem cell transplantation</subject><subject>Survival Analysis</subject><subject>Trisomy</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkt2L1DAUxYMo7jj65rMEBPHBjvlsGx-EcXFXYRZf9Dlk0tuZrG1Sk1bY_950Z11nZCmk4d7fOe1NDkIvKVlRwuv3HUwrRmi1oow-QgsqqrKQUtLHaEHquipKxcQZepbSNSFzs3yKzlgtBC9JuUDuEnwYbwYowjTa0AO2IUbozOiCT9h5PEDjzBidxeurzQc87gG7fjB2xKHFBvfBhxR60-GfJt7cWs2qLMilrCg-XVxhRoh4jp60pkvw4u69RD8uPn8__1Jsvl1-PV9vCitFPRYVKG4lENIo2xphqJCkoao1Vcm5ElvFpMibCpixhptcz2jLtkbJqiEl8CX6ePAdpm0PjQU_RtPpIbo-_6AOxunTjnd7vQu_tayY4pxkg7d3BjH8miCNunfJQtcZD2FKmtaKzVxeluj1f-h1mKLP42mqKk4oUTX7R-1MB9r5NuTv2tlUryWtZEnzRJlaPUDlp4He2eChdbl-InhzJNiD6cZ9Ct10e3On4LsDaGNIKUJ7fxiU6DlDOmdIzxnSOUMZf3V8gPfw39BkoDgAKbf8DuLR1A8Z_gHDw842</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Rasche, M</creator><creator>von Neuhoff, C</creator><creator>Dworzak, M</creator><creator>Bourquin, J-P</creator><creator>Bradtke, J</creator><creator>Göhring, G</creator><creator>Escherich, G</creator><creator>Fleischhack, G</creator><creator>Graf, N</creator><creator>Gruhn, B</creator><creator>Haas, O A</creator><creator>Klingebiel, T</creator><creator>Kremens, B</creator><creator>Lehrnbecher, T</creator><creator>von Stackelberg, A</creator><creator>Tchinda, J</creator><creator>Zemanova, Z</creator><creator>Thiede, C</creator><creator>von Neuhoff, N</creator><creator>Zimmermann, M</creator><creator>Creutzig, U</creator><creator>Reinhardt, D</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><orcidid>https://orcid.org/0000-0002-2248-323X</orcidid></search><sort><creationdate>20171201</creationdate><title>Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004</title><author>Rasche, M ; von Neuhoff, C ; Dworzak, M ; Bourquin, J-P ; Bradtke, J ; Göhring, G ; Escherich, G ; Fleischhack, G ; Graf, N ; Gruhn, B ; Haas, O A ; Klingebiel, T ; Kremens, B ; Lehrnbecher, T ; von Stackelberg, A ; Tchinda, J ; Zemanova, Z ; Thiede, C ; von Neuhoff, N ; Zimmermann, M ; Creutzig, U ; Reinhardt, D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c548t-7e93c5e00d9cfa4a1450d19fa763394b92543397e2aca3afa700df2ba957d06e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>14/32</topic><topic>631/208/1405</topic><topic>631/67/68</topic><topic>692/308/2056</topic><topic>692/4028/67/2332</topic><topic>692/53/2422</topic><topic>692/699/67</topic><topic>692/699/67/1990/283/1897</topic><topic>Aberration</topic><topic>Acute myelocytic leukemia</topic><topic>Acute myeloid leukemia</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Children</topic><topic>Chromosome Aberrations</topic><topic>Chromosomes, Human, Pair 7</topic><topic>Clinical Trials as Topic</topic><topic>Critical Care Medicine</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Genetic Variation</topic><topic>Genotype</topic><topic>Hematology</topic><topic>Humans</topic><topic>Hypodiploidy</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Karyotype</topic><topic>Karyotypes</topic><topic>Karyotyping</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - diagnosis</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - mortality</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Monosomy</topic><topic>Mutation</topic><topic>Myeloid leukemia</topic><topic>Oncology</topic><topic>Original</topic><topic>original-article</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Regression analysis</topic><topic>Risk factors</topic><topic>Stem cell transplantation</topic><topic>Survival Analysis</topic><topic>Trisomy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rasche, M</creatorcontrib><creatorcontrib>von Neuhoff, C</creatorcontrib><creatorcontrib>Dworzak, M</creatorcontrib><creatorcontrib>Bourquin, J-P</creatorcontrib><creatorcontrib>Bradtke, J</creatorcontrib><creatorcontrib>Göhring, G</creatorcontrib><creatorcontrib>Escherich, G</creatorcontrib><creatorcontrib>Fleischhack, G</creatorcontrib><creatorcontrib>Graf, N</creatorcontrib><creatorcontrib>Gruhn, B</creatorcontrib><creatorcontrib>Haas, O A</creatorcontrib><creatorcontrib>Klingebiel, T</creatorcontrib><creatorcontrib>Kremens, B</creatorcontrib><creatorcontrib>Lehrnbecher, T</creatorcontrib><creatorcontrib>von Stackelberg, A</creatorcontrib><creatorcontrib>Tchinda, J</creatorcontrib><creatorcontrib>Zemanova, Z</creatorcontrib><creatorcontrib>Thiede, C</creatorcontrib><creatorcontrib>von Neuhoff, N</creatorcontrib><creatorcontrib>Zimmermann, M</creatorcontrib><creatorcontrib>Creutzig, U</creatorcontrib><creatorcontrib>Reinhardt, D</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 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T</au><au>Kremens, B</au><au>Lehrnbecher, T</au><au>von Stackelberg, A</au><au>Tchinda, J</au><au>Zemanova, Z</au><au>Thiede, C</au><au>von Neuhoff, N</au><au>Zimmermann, M</au><au>Creutzig, U</au><au>Reinhardt, D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2017-12-01</date><risdate>2017</risdate><volume>31</volume><issue>12</issue><spage>2807</spage><epage>2814</epage><pages>2807-2814</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>We conducted a cytogenetic analysis of 642 children with
de novo
acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK
+
), complex (CK
+
) and hypodiploid (HK
+
) karyotypes, individually and in combination. Multivariate regression analysis identified in particular MK
+
(
n
=22) as a new independent risk factor for poor event-free survival (EFS 23±9% vs 53±2% for all other patients,
P
=0.0003), even after exclusion of four patients with monosomy 7 (EFS 28±11%,
P
=0.0081). CK
+
patients without MK had a better prognosis (
n
=47, EFS 47±8%,
P
=0.46) than those with MK
+
(
n
=12, EFS 25±13%,
P
=0.024). HK
+
(
n
=37, EFS 44±8% for total cohort,
P
=0.3) influenced outcome only when t(8;21) patients were excluded (remaining
n
=16, EFS 9±8%,
P
<0.0001). An extremely poor outcome was observed for MK
+
/HK
+
patients (
n
=10, EFS 10±10%,
P
<0.0001). Finally, isolated trisomy 8 was also associated with low EFS (
n
=16, EFS 25±11%,
P
=0.0091). In conclusion, monosomal karyotype is a strong and independent predictor for high-risk pediatric AML. In addition, isolated trisomy 8 and hypodiploidy without t(8;21) coincide with dismal outcome. These results have important implications for risk stratification and should be further validated in independent pediatric cohorts.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28443606</pmid><doi>10.1038/leu.2017.121</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-2248-323X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2017-12, Vol.31 (12), p.2807-2814 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5729330 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | 14/32 631/208/1405 631/67/68 692/308/2056 692/4028/67/2332 692/53/2422 692/699/67 692/699/67/1990/283/1897 Aberration Acute myelocytic leukemia Acute myeloid leukemia Cancer Research Care and treatment Children Chromosome Aberrations Chromosomes, Human, Pair 7 Clinical Trials as Topic Critical Care Medicine Diagnosis Female Genetic Variation Genotype Hematology Humans Hypodiploidy Intensive Internal Medicine Karyotype Karyotypes Karyotyping Leukemia Leukemia, Myeloid, Acute - diagnosis Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - mortality Male Medical prognosis Medicine Medicine & Public Health Monosomy Mutation Myeloid leukemia Oncology Original original-article Patients Pediatrics Polymerase chain reaction Prognosis Regression analysis Risk factors Stem cell transplantation Survival Analysis Trisomy |
| title | Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T19%3A23%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genotype-outcome%20correlations%20in%20pediatric%20AML:%20the%20impact%20of%20a%20monosomal%20karyotype%20in%20trial%20AML-BFM%202004&rft.jtitle=Leukemia&rft.au=Rasche,%20M&rft.date=2017-12-01&rft.volume=31&rft.issue=12&rft.spage=2807&rft.epage=2814&rft.pages=2807-2814&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/leu.2017.121&rft_dat=%3Cgale_pubme%3EA517561433%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1973010982&rft_id=info:pmid/28443606&rft_galeid=A517561433&rfr_iscdi=true |