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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase</title>
<author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name>
<affiliation><nlm:aff id="aff1">Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Saglio, Giuseppe" sort="Saglio, Giuseppe" uniqKey="Saglio G" first="Giuseppe" last="Saglio">Giuseppe Saglio</name>
<affiliation><nlm:aff id="aff2">San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Larson, Richard A" sort="Larson, Richard A" uniqKey="Larson R" first="Richard A." last="Larson">Richard A. Larson</name>
<affiliation><nlm:aff id="aff3">University of Chicago Medical Center, Chicago, IL;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kim, Dong Wook" sort="Kim, Dong Wook" uniqKey="Kim D" first="Dong-Wook" last="Kim">Dong-Wook Kim</name>
<affiliation><nlm:aff id="aff4">St. Mary’s Hospital, Catholic University of Korea, Seoul, Korea;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Etienne, Gabriel" sort="Etienne, Gabriel" uniqKey="Etienne G" first="Gabriel" last="Etienne">Gabriel Etienne</name>
<affiliation><nlm:aff id="aff5">Institut Bergonié, Bordeaux, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rosti, Gianantonio" sort="Rosti, Gianantonio" uniqKey="Rosti G" first="Gianantonio" last="Rosti">Gianantonio Rosti</name>
<affiliation><nlm:aff id="aff6">Institute L. e A. Seràgnoli, University of Bologna, Bologna, Italy;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="De Souza, Carmino" sort="De Souza, Carmino" uniqKey="De Souza C" first="Carmino" last="De Souza">Carmino De Souza</name>
<affiliation><nlm:aff id="aff7">UNICAMP, University of Campinas-SP, Campinas, Brazil;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kurokawa, Mineo" sort="Kurokawa, Mineo" uniqKey="Kurokawa M" first="Mineo" last="Kurokawa">Mineo Kurokawa</name>
<affiliation><nlm:aff id="aff8">University of Tokyo Hospital, Tokyo, Japan;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kalaycio, Matt E" sort="Kalaycio, Matt E" uniqKey="Kalaycio M" first="Matt E." last="Kalaycio">Matt E. Kalaycio</name>
<affiliation><nlm:aff id="aff9">Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoenekopp, Albert" sort="Hoenekopp, Albert" uniqKey="Hoenekopp A" first="Albert" last="Hoenekopp">Albert Hoenekopp</name>
<affiliation><nlm:aff id="aff10">Novartis Pharma AG, Basel, Switzerland;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fan, Xiaolin" sort="Fan, Xiaolin" uniqKey="Fan X" first="Xiaolin" last="Fan">Xiaolin Fan</name>
<affiliation><nlm:aff id="aff11">Novartis Pharmaceuticals Corporation, East Hanover, NJ;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shou, Yaping" sort="Shou, Yaping" uniqKey="Shou Y" first="Yaping" last="Shou">Yaping Shou</name>
<affiliation><nlm:aff id="aff11">Novartis Pharmaceuticals Corporation, East Hanover, NJ;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff12">MD Anderson Cancer Center, University of Texas, Houston, TX</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</name>
<affiliation><nlm:aff id="aff13">Centre for Cancer Biology, SA Pathology, University of Adelaide, Adelaide, SA, Australia</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">23502220</idno>
<idno type="pmc">4915803</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915803</idno>
<idno type="RBID">PMC:4915803</idno>
<idno type="doi">10.1182/blood-2012-04-423418</idno>
<date when="2013">2013</date>
<idno type="wicri:Area/Pmc/Corpus">000434</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000434</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase</title>
<author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name>
<affiliation><nlm:aff id="aff1">Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Saglio, Giuseppe" sort="Saglio, Giuseppe" uniqKey="Saglio G" first="Giuseppe" last="Saglio">Giuseppe Saglio</name>
<affiliation><nlm:aff id="aff2">San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Larson, Richard A" sort="Larson, Richard A" uniqKey="Larson R" first="Richard A." last="Larson">Richard A. Larson</name>
<affiliation><nlm:aff id="aff3">University of Chicago Medical Center, Chicago, IL;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kim, Dong Wook" sort="Kim, Dong Wook" uniqKey="Kim D" first="Dong-Wook" last="Kim">Dong-Wook Kim</name>
<affiliation><nlm:aff id="aff4">St. Mary’s Hospital, Catholic University of Korea, Seoul, Korea;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Etienne, Gabriel" sort="Etienne, Gabriel" uniqKey="Etienne G" first="Gabriel" last="Etienne">Gabriel Etienne</name>
<affiliation><nlm:aff id="aff5">Institut Bergonié, Bordeaux, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rosti, Gianantonio" sort="Rosti, Gianantonio" uniqKey="Rosti G" first="Gianantonio" last="Rosti">Gianantonio Rosti</name>
<affiliation><nlm:aff id="aff6">Institute L. e A. Seràgnoli, University of Bologna, Bologna, Italy;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="De Souza, Carmino" sort="De Souza, Carmino" uniqKey="De Souza C" first="Carmino" last="De Souza">Carmino De Souza</name>
<affiliation><nlm:aff id="aff7">UNICAMP, University of Campinas-SP, Campinas, Brazil;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kurokawa, Mineo" sort="Kurokawa, Mineo" uniqKey="Kurokawa M" first="Mineo" last="Kurokawa">Mineo Kurokawa</name>
<affiliation><nlm:aff id="aff8">University of Tokyo Hospital, Tokyo, Japan;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kalaycio, Matt E" sort="Kalaycio, Matt E" uniqKey="Kalaycio M" first="Matt E." last="Kalaycio">Matt E. Kalaycio</name>
<affiliation><nlm:aff id="aff9">Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoenekopp, Albert" sort="Hoenekopp, Albert" uniqKey="Hoenekopp A" first="Albert" last="Hoenekopp">Albert Hoenekopp</name>
<affiliation><nlm:aff id="aff10">Novartis Pharma AG, Basel, Switzerland;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fan, Xiaolin" sort="Fan, Xiaolin" uniqKey="Fan X" first="Xiaolin" last="Fan">Xiaolin Fan</name>
<affiliation><nlm:aff id="aff11">Novartis Pharmaceuticals Corporation, East Hanover, NJ;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shou, Yaping" sort="Shou, Yaping" uniqKey="Shou Y" first="Yaping" last="Shou">Yaping Shou</name>
<affiliation><nlm:aff id="aff11">Novartis Pharmaceuticals Corporation, East Hanover, NJ;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff12">MD Anderson Cancer Center, University of Texas, Houston, TX</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</name>
<affiliation><nlm:aff id="aff13">Centre for Cancer Biology, SA Pathology, University of Adelaide, Adelaide, SA, Australia</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Blood</title>
<idno type="ISSN">0006-4971</idno>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Key Points</title>
<p><list list-type="bullet"><list-item><p>Frontline nilotinib led to fewer, less diverse BCR-ABL mutations than imatinib in patients with chronic myeloid leukemia in chronic phase.</p>
</list-item>
<list-item><p>Rates of progression to accelerated phase/blast crisis were lower with nilotinib than imatinib in patients with emergent BCR-ABL mutations.</p>
</list-item>
</list>
</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Blood</journal-id>
<journal-id journal-id-type="iso-abbrev">Blood</journal-id>
<journal-id journal-id-type="hwp">bloodjournal</journal-id>
<journal-id journal-id-type="pmc">blood</journal-id>
<journal-id journal-id-type="publisher-id">Blood</journal-id>
<journal-title-group><journal-title>Blood</journal-title>
</journal-title-group>
<issn pub-type="ppub">0006-4971</issn>
<issn pub-type="epub">1528-0020</issn>
<publisher><publisher-name>American Society of Hematology</publisher-name>
<publisher-loc>Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23502220</article-id>
<article-id pub-id-type="pmc">4915803</article-id>
<article-id pub-id-type="publisher-id">2012/423418</article-id>
<article-id pub-id-type="doi">10.1182/blood-2012-04-423418</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Myeloid Neoplasia</subject>
</subj-group>
</article-categories>
<title-group><article-title>Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Hochhaus</surname>
<given-names>Andreas</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Saglio</surname>
<given-names>Giuseppe</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Larson</surname>
<given-names>Richard A.</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kim</surname>
<given-names>Dong-Wook</given-names>
</name>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Etienne</surname>
<given-names>Gabriel</given-names>
</name>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rosti</surname>
<given-names>Gianantonio</given-names>
</name>
<xref ref-type="aff" rid="aff6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>De Souza</surname>
<given-names>Carmino</given-names>
</name>
<xref ref-type="aff" rid="aff7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kurokawa</surname>
<given-names>Mineo</given-names>
</name>
<xref ref-type="aff" rid="aff8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kalaycio</surname>
<given-names>Matt E.</given-names>
</name>
<xref ref-type="aff" rid="aff9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hoenekopp</surname>
<given-names>Albert</given-names>
</name>
<xref ref-type="aff" rid="aff10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fan</surname>
<given-names>Xiaolin</given-names>
</name>
<xref ref-type="aff" rid="aff11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shou</surname>
<given-names>Yaping</given-names>
</name>
<xref ref-type="aff" rid="aff11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kantarjian</surname>
<given-names>Hagop M.</given-names>
</name>
<xref ref-type="aff" rid="aff12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hughes</surname>
<given-names>Timothy P.</given-names>
</name>
<xref ref-type="aff" rid="aff13">13</xref>
</contrib>
<aff id="aff1"><label>1</label>
Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany;</aff>
<aff id="aff2"><label>2</label>
San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy;</aff>
<aff id="aff3"><label>3</label>
University of Chicago Medical Center, Chicago, IL;</aff>
<aff id="aff4"><label>4</label>
St. Mary’s Hospital, Catholic University of Korea, Seoul, Korea;</aff>
<aff id="aff5"><label>5</label>
Institut Bergonié, Bordeaux, France;</aff>
<aff id="aff6"><label>6</label>
Institute L. e A. Seràgnoli, University of Bologna, Bologna, Italy;</aff>
<aff id="aff7"><label>7</label>
UNICAMP, University of Campinas-SP, Campinas, Brazil;</aff>
<aff id="aff8"><label>8</label>
University of Tokyo Hospital, Tokyo, Japan;</aff>
<aff id="aff9"><label>9</label>
Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH;</aff>
<aff id="aff10"><label>10</label>
Novartis Pharma AG, Basel, Switzerland;</aff>
<aff id="aff11"><label>11</label>
Novartis Pharmaceuticals Corporation, East Hanover, NJ;</aff>
<aff id="aff12"><label>12</label>
MD Anderson Cancer Center, University of Texas, Houston, TX; and</aff>
<aff id="aff13"><label>13</label>
Centre for Cancer Biology, SA Pathology, University of Adelaide, Adelaide, SA, Australia</aff>
</contrib-group>
<pub-date pub-type="ppub"><day>02</day>
<month>5</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epreprint"><day>15</day>
<month>3</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>02</day>
<month>5</month>
<year>2013</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>121</volume>
<issue>18</issue>
<fpage>3703</fpage>
<lpage>3708</lpage>
<history><date date-type="received"><day>12</day>
<month>4</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>04</day>
<month>3</month>
<year>2013</year>
</date>
</history>
<permissions><copyright-statement>© 2013 by The American Society of Hematology</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="3703.pdf"></self-uri>
<abstract abstract-type="executive-summary"><title>Key Points</title>
<p><list list-type="bullet"><list-item><p>Frontline nilotinib led to fewer, less diverse BCR-ABL mutations than imatinib in patients with chronic myeloid leukemia in chronic phase.</p>
</list-item>
<list-item><p>Rates of progression to accelerated phase/blast crisis were lower with nilotinib than imatinib in patients with emergent BCR-ABL mutations.</p>
</list-item>
</list>
</p>
</abstract>
<abstract><p>In patients with chronic myeloid leukemia, BCR-ABL mutations contribute to resistance to tyrosine kinase inhibitor therapy. We examined the occurrence of treatment-emergent mutations and their impact on response in patients from the ENESTnd phase 3 trial. At the 3-year data cutoff, mutations were detected in approximately twice as many patients (21) on imatinib 400 mg once daily as on nilotinib (11 patients each on nilotinib 300 mg twice daily and nilotinib 400 mg twice daily). The majority of mutations occurred in patients with intermediate or high Sokal scores. Most mutations (14 [66.7%]) emerging during imatinib treatment were imatinib-resistant and nilotinib-sensitive. Incidence of the T315I mutation was low (found in 3, 2, and 3 patients on nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib, respectively) and mostly occurred in patients with high Sokal scores. Of the patients with emergent mutations, 1 of 11, 2 of 11, and 7 of 21 patients on nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib, respectively, progressed to accelerated phase/blast crisis (AP/BC) on treatment. Overall, nilotinib led to fewer treatment-emergent BCR-ABL mutations than imatinib and reduced rates of progression to AP/BC in patients with these mutations. (<ext-link ext-link-type="uri" xlink:href="Clinicaltrials.gov">Clinicaltrials.gov</ext-link>
NCT00471497).</p>
</abstract>
<counts><page-count count="6"></page-count>
</counts>
<custom-meta-group><custom-meta><meta-name>access</meta-name>
<meta-value>free</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
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