Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)
Identifieur interne : 000844 ( Ncbi/Merge ); précédent : 000843; suivant : 000845Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)
Auteurs : Timothy P. Hughes [Australie] ; Andreas Hochhaus [Allemagne] ; Susan Branford [Australie] ; Martin C. Müller [Allemagne] ; Jaspal S. Kaeda [Portugal] ; Letizia Foroni [Royaume-Uni] ; Brian J. Druker [États-Unis] ; François Guilhot [France] ; Richard A. Larson [États-Unis] ; Stephen G. O'Brien [Royaume-Uni] ; Marc S. Rudoltz [États-Unis] ; Manisha Mone [États-Unis] ; Elisabeth Wehrle [Suisse] ; Vijay Modur [États-Unis] ; John M. Goldman [Royaume-Uni] ; Jerald P. Radich [États-Unis]Source :
- Blood [ 0006-4971 ] ; 2010.
Abstract
This study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases in
Url:
DOI: 10.1182/blood-2010-03-273979
PubMed: 20679528
PubMed Central: 3266053
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)</title><author><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide</wicri:regionArea><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name><affiliation wicri:level="1"><nlm:aff id="aff2">Abt Hämatologie und internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abt Hämatologie und internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name><affiliation wicri:level="1"><nlm:aff id="aff3">Molecular Pathology, SA Pathology, Adelaide, Australia and School of Medicine, University of Adelaide, Adelaide, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Molecular Pathology, SA Pathology, Adelaide, Australia and School of Medicine, University of Adelaide, Adelaide</wicri:regionArea><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Muller, Martin C" sort="Muller, Martin C" uniqKey="Muller M" first="Martin C." last="Müller">Martin C. 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Larson</name><affiliation wicri:level="2"><nlm:aff id="aff9">University of Chicago, Chicago, IL;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>University of Chicago, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="O Brien, Stephen G" sort="O Brien, Stephen G" uniqKey="O Brien S" first="Stephen G." last="O'Brien">Stephen G. O'Brien</name><affiliation wicri:level="1"><nlm:aff id="aff10">Newcastle University Medical School, Newcastle, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Newcastle University Medical School, Newcastle</wicri:regionArea><wicri:noRegion>Newcastle</wicri:noRegion></affiliation></author><author><name sortKey="Rudoltz, Marc S" sort="Rudoltz, Marc S" uniqKey="Rudoltz M" first="Marc S." last="Rudoltz">Marc S. Rudoltz</name><affiliation wicri:level="2"><nlm:aff id="aff11">Novartis Pharmaceuticals Corporation, East Hanover, NJ;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Novartis Pharmaceuticals Corporation, East Hanover</wicri:cityArea></affiliation></author><author><name sortKey="Mone, Manisha" sort="Mone, Manisha" uniqKey="Mone M" first="Manisha" last="Mone">Manisha Mone</name><affiliation wicri:level="2"><nlm:aff id="aff11">Novartis Pharmaceuticals Corporation, East Hanover, NJ;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Novartis Pharmaceuticals Corporation, East Hanover</wicri:cityArea></affiliation></author><author><name sortKey="Wehrle, Elisabeth" sort="Wehrle, Elisabeth" uniqKey="Wehrle E" first="Elisabeth" last="Wehrle">Elisabeth Wehrle</name><affiliation wicri:level="1"><nlm:aff id="aff12">Novartis Pharma AG, Basel, Switzerland;</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Novartis Pharma AG, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation></author><author><name sortKey="Modur, Vijay" sort="Modur, Vijay" uniqKey="Modur V" first="Vijay" last="Modur">Vijay Modur</name><affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="aff13">Novartis Institute of Biomedical Research, Cambridge, MA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Novartis Institute of Biomedical Research, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Goldman, John M" sort="Goldman, John M" uniqKey="Goldman J" first="John M." last="Goldman">John M. Goldman</name><affiliation wicri:level="3"><nlm:aff id="aff6">Haematology Department, Hammersmith Hospital, London, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Haematology Department, Hammersmith Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Radich, Jerald P" sort="Radich, Jerald P" uniqKey="Radich J" first="Jerald P." last="Radich">Jerald P. 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Hughes</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide</wicri:regionArea><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name><affiliation wicri:level="1"><nlm:aff id="aff2">Abt Hämatologie und internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Abt Hämatologie und internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name><affiliation wicri:level="1"><nlm:aff id="aff3">Molecular Pathology, SA Pathology, Adelaide, Australia and School of Medicine, University of Adelaide, Adelaide, Australia;</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Molecular Pathology, SA Pathology, Adelaide, Australia and School of Medicine, University of Adelaide, Adelaide</wicri:regionArea><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Muller, Martin C" sort="Muller, Martin C" uniqKey="Muller M" first="Martin C." last="Müller">Martin C. Müller</name><affiliation wicri:level="3"><nlm:aff id="aff4">III Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>III Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Kaeda, Jaspal S" sort="Kaeda, Jaspal S" uniqKey="Kaeda J" first="Jaspal S." last="Kaeda">Jaspal S. Kaeda</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Hematology, Central Hospital of Coimbra, Coimbra, Portugal;</nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>Department of Hematology, Central Hospital of Coimbra, Coimbra</wicri:regionArea><wicri:noRegion>Coimbra</wicri:noRegion></affiliation></author><author><name sortKey="Foroni, Letizia" sort="Foroni, Letizia" uniqKey="Foroni L" first="Letizia" last="Foroni">Letizia Foroni</name><affiliation wicri:level="3"><nlm:aff id="aff6">Haematology Department, Hammersmith Hospital, London, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Haematology Department, Hammersmith Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name><affiliation wicri:level="2"><nlm:aff id="aff7">Knight Cancer Institute, Oregon Health & Science University, Portland, OR;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oregon</region></placeName><wicri:cityArea>Knight Cancer Institute, Oregon Health & Science University, Portland</wicri:cityArea></affiliation></author><author><name sortKey="Guilhot, Francois" sort="Guilhot, Francois" uniqKey="Guilhot F" first="François" last="Guilhot">François Guilhot</name><affiliation wicri:level="3"><nlm:aff id="aff8">Centre d'Investigation Clinique CIC P 802, Inserm, Centre Hospitalier Universitaire de Poitiers, Poitiers, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre d'Investigation Clinique CIC P 802, Inserm, Centre Hospitalier Universitaire de Poitiers, Poitiers</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Poitou-Charentes</region><settlement type="city">Poitiers</settlement></placeName></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 wicri:level="2"><nlm:aff id="aff9">University of Chicago, Chicago, IL;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>University of Chicago, Chicago</wicri:cityArea></affiliation></author><author><name sortKey="O Brien, Stephen G" sort="O Brien, Stephen G" uniqKey="O Brien S" first="Stephen G." last="O'Brien">Stephen G. O'Brien</name><affiliation wicri:level="1"><nlm:aff id="aff10">Newcastle University Medical School, Newcastle, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Newcastle University Medical School, Newcastle</wicri:regionArea><wicri:noRegion>Newcastle</wicri:noRegion></affiliation></author><author><name sortKey="Rudoltz, Marc S" sort="Rudoltz, Marc S" uniqKey="Rudoltz M" first="Marc S." last="Rudoltz">Marc S. Rudoltz</name><affiliation wicri:level="2"><nlm:aff id="aff11">Novartis Pharmaceuticals Corporation, East Hanover, NJ;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Novartis Pharmaceuticals Corporation, East Hanover</wicri:cityArea></affiliation></author><author><name sortKey="Mone, Manisha" sort="Mone, Manisha" uniqKey="Mone M" first="Manisha" last="Mone">Manisha Mone</name><affiliation wicri:level="2"><nlm:aff id="aff11">Novartis Pharmaceuticals Corporation, East Hanover, NJ;</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Novartis Pharmaceuticals Corporation, East Hanover</wicri:cityArea></affiliation></author><author><name sortKey="Wehrle, Elisabeth" sort="Wehrle, Elisabeth" uniqKey="Wehrle E" first="Elisabeth" last="Wehrle">Elisabeth Wehrle</name><affiliation wicri:level="1"><nlm:aff id="aff12">Novartis Pharma AG, Basel, Switzerland;</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Novartis Pharma AG, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation></author><author><name sortKey="Modur, Vijay" sort="Modur, Vijay" uniqKey="Modur V" first="Vijay" last="Modur">Vijay Modur</name><affiliation wicri:level="2"><nlm:aff wicri:cut="; and" id="aff13">Novartis Institute of Biomedical Research, Cambridge, MA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Novartis Institute of Biomedical Research, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Goldman, John M" sort="Goldman, John M" uniqKey="Goldman J" first="John M." last="Goldman">John M. Goldman</name><affiliation wicri:level="3"><nlm:aff id="aff6">Haematology Department, Hammersmith Hospital, London, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Haematology Department, Hammersmith Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Radich, Jerald P" sort="Radich, Jerald P" uniqKey="Radich J" first="Jerald P." last="Radich">Jerald P. Radich</name><affiliation wicri:level="2"><nlm:aff id="aff14">Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea></affiliation></author></analytic><series><title level="j">Blood</title><idno type="ISSN">0006-4971</idno><idno type="eISSN">1528-0020</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>This study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases in <italic>BCR-ABL</italic> transcripts over time. Analyses of event-free survival (EFS) and time to progression to accelerated phase/blast crisis (AP/BC) at 7 years were based on molecular responses using the international scale (IS) at 6-, 12-, and 18-month landmarks. Patients with <italic>BCR-ABL</italic> transcripts > 10% at 6 months and > 1% at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups. Conversely, patients who achieved major molecular response [MMR: <italic>BCR-ABL</italic> (IS) ≤ 0.1%] by 18 months enjoyed remarkably durable responses, with no progression to AP/BC and 95% EFS at 7 years. The probability of loss of complete cytogenetic response by 7 years was only 3% for patients in MMR at 18 months versus 26% for patients with complete cytogenetic response but not MMR (<italic>P</italic> < .001). This study shows a strong association between the degree to which <italic>BCR-ABL</italic> transcript numbers are reduced by therapy and long-term clinical outcome, supporting the use of time-dependent molecular measures to determine optimal response to therapy. This study is registered at <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link> as NCT00006343.</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="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">20679528</article-id><article-id pub-id-type="pmc">3266053</article-id><article-id pub-id-type="publisher-id">2010/273979</article-id><article-id pub-id-type="doi">10.1182/blood-2010-03-273979</article-id><article-categories><subj-group subj-group-type="heading"><subject>Clinical Trials and Observations</subject></subj-group><series-title>Clinical Trials and Observations</series-title></article-categories><title-group><article-title>Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Hughes</surname><given-names>Timothy P.</given-names></name><xref ref-type="author-notes" rid="FN1">*</xref><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hochhaus</surname><given-names>Andreas</given-names></name><xref ref-type="author-notes" rid="FN1">*</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Branford</surname><given-names>Susan</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Müller</surname><given-names>Martin C.</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Kaeda</surname><given-names>Jaspal S.</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Foroni</surname><given-names>Letizia</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Druker</surname><given-names>Brian J.</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Guilhot</surname><given-names>François</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Larson</surname><given-names>Richard A.</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>O'Brien</surname><given-names>Stephen G.</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author"><name><surname>Rudoltz</surname><given-names>Marc S.</given-names></name><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author"><name><surname>Mone</surname><given-names>Manisha</given-names></name><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author"><name><surname>Wehrle</surname><given-names>Elisabeth</given-names></name><xref ref-type="aff" rid="aff12">12</xref></contrib><contrib contrib-type="author"><name><surname>Modur</surname><given-names>Vijay</given-names></name><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Goldman</surname><given-names>John M.</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Radich</surname><given-names>Jerald P.</given-names></name><xref ref-type="aff" rid="aff14">14</xref><on-behalf-of>on behalf of the IRIS investigators</on-behalf-of></contrib><aff id="aff1"><label>1</label>Department of Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide, Australia;</aff><aff id="aff2"><label>2</label>Abt Hämatologie und internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany;</aff><aff id="aff3"><label>3</label>Molecular Pathology, SA Pathology, Adelaide, Australia and School of Medicine, University of Adelaide, Adelaide, Australia;</aff><aff id="aff4"><label>4</label>III Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany;</aff><aff id="aff5"><label>5</label>Department of Hematology, Central Hospital of Coimbra, Coimbra, Portugal;</aff><aff id="aff6"><label>6</label>Haematology Department, Hammersmith Hospital, London, United Kingdom;</aff><aff id="aff7"><label>7</label>Knight Cancer Institute, Oregon Health & Science University, Portland, OR;</aff><aff id="aff8"><label>8</label>Centre d'Investigation Clinique CIC P 802, Inserm, Centre Hospitalier Universitaire de Poitiers, Poitiers, France;</aff><aff id="aff9"><label>9</label>University of Chicago, Chicago, IL;</aff><aff id="aff10"><label>10</label>Newcastle University Medical School, Newcastle, United Kingdom;</aff><aff id="aff11"><label>11</label>Novartis Pharmaceuticals Corporation, East Hanover, NJ;</aff><aff id="aff12"><label>12</label>Novartis Pharma AG, Basel, Switzerland;</aff><aff id="aff13"><label>13</label>Novartis Institute of Biomedical Research, Cambridge, MA; and</aff><aff id="aff14"><label>14</label>Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA</aff></contrib-group><author-notes><fn fn-type="equal" id="FN1"><label>*</label><p>T.H. and A.H. contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><day>11</day><month>11</month><year>2010</year></pub-date><pub-date pub-type="epreprint"><day>2</day><month>8</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>11</day><month>11</month><year>2011</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>116</volume><issue>19</issue><fpage>3758</fpage><lpage>3765</lpage><history><date date-type="received"><day>19</day><month>3</month><year>2010</year></date><date date-type="accepted"><day>19</day><month>7</month><year>2010</year></date></history><permissions><copyright-statement>© 2010 by The American Society of Hematology</copyright-statement><copyright-year>2010</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zh804510003758.pdf"></self-uri><abstract><p>This study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases in <italic>BCR-ABL</italic> transcripts over time. Analyses of event-free survival (EFS) and time to progression to accelerated phase/blast crisis (AP/BC) at 7 years were based on molecular responses using the international scale (IS) at 6-, 12-, and 18-month landmarks. Patients with <italic>BCR-ABL</italic> transcripts > 10% at 6 months and > 1% at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups. Conversely, patients who achieved major molecular response [MMR: <italic>BCR-ABL</italic> (IS) ≤ 0.1%] by 18 months enjoyed remarkably durable responses, with no progression to AP/BC and 95% EFS at 7 years. The probability of loss of complete cytogenetic response by 7 years was only 3% for patients in MMR at 18 months versus 26% for patients with complete cytogenetic response but not MMR (<italic>P</italic> < .001). This study shows a strong association between the degree to which <italic>BCR-ABL</italic> transcript numbers are reduced by therapy and long-term clinical outcome, supporting the use of time-dependent molecular measures to determine optimal response to therapy. This study is registered at <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link> as NCT00006343.</p></abstract></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Portugal</li><li>Royaume-Uni</li><li>Suisse</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Bade-Wurtemberg</li><li>District de Karlsruhe</li><li>Grand Londres</li><li>Illinois</li><li>Massachusetts</li><li>New Jersey</li><li>Nouvelle-Aquitaine</li><li>Oregon</li><li>Poitou-Charentes</li><li>Washington (État)</li></region><settlement><li>Londres</li><li>Mannheim</li><li>Poitiers</li></settlement></list><tree><country name="Australie"><noRegion><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</name></noRegion><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name></country><country name="Allemagne"><noRegion><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name></noRegion><name sortKey="Muller, Martin C" sort="Muller, Martin C" uniqKey="Muller M" first="Martin C." last="Müller">Martin C. Müller</name></country><country name="Portugal"><noRegion><name sortKey="Kaeda, Jaspal S" sort="Kaeda, Jaspal S" uniqKey="Kaeda J" first="Jaspal S." last="Kaeda">Jaspal S. Kaeda</name></noRegion></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Foroni, Letizia" sort="Foroni, Letizia" uniqKey="Foroni L" first="Letizia" last="Foroni">Letizia Foroni</name></region><name sortKey="Goldman, John M" sort="Goldman, John M" uniqKey="Goldman J" first="John M." last="Goldman">John M. Goldman</name><name sortKey="O Brien, Stephen G" sort="O Brien, Stephen G" uniqKey="O Brien S" first="Stephen G." last="O'Brien">Stephen G. O'Brien</name></country><country name="États-Unis"><region name="Oregon"><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name></region><name sortKey="Larson, Richard A" sort="Larson, Richard A" uniqKey="Larson R" first="Richard A." last="Larson">Richard A. Larson</name><name sortKey="Modur, Vijay" sort="Modur, Vijay" uniqKey="Modur V" first="Vijay" last="Modur">Vijay Modur</name><name sortKey="Mone, Manisha" sort="Mone, Manisha" uniqKey="Mone M" first="Manisha" last="Mone">Manisha Mone</name><name sortKey="Radich, Jerald P" sort="Radich, Jerald P" uniqKey="Radich J" first="Jerald P." last="Radich">Jerald P. Radich</name><name sortKey="Rudoltz, Marc S" sort="Rudoltz, Marc S" uniqKey="Rudoltz M" first="Marc S." last="Rudoltz">Marc S. Rudoltz</name></country><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Guilhot, Francois" sort="Guilhot, Francois" uniqKey="Guilhot F" first="François" last="Guilhot">François Guilhot</name></region></country><country name="Suisse"><noRegion><name sortKey="Wehrle, Elisabeth" sort="Wehrle, Elisabeth" uniqKey="Wehrle E" first="Elisabeth" last="Wehrle">Elisabeth Wehrle</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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