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 : 007757 ( Main/Exploration ); précédent : 007756; suivant : 007758Long-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.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
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 BCR-ABL transcripts overtime. 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 BCR-ABL 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: BCR-ABL (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 (P < .001). This study shows a strong association between the degree to which BCR-ABL 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.
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Affiliations:
- Allemagne, Australie, France, Portugal, Royaume-Uni, Suisse, États-Unis
- Angleterre, Bade-Wurtemberg, District de Karlsruhe, Grand Londres, Nouvelle-Aquitaine, Poitou-Charentes
- Londres, Mannheim, Poitiers
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">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"><inist:fA14 i1="01"><s1>Department of Haematology, SA Pathology, Royal Adelaide Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>1 aut.</sZ></inist:fA14><country>Australie</country><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"><inist:fA14 i1="02"><s1>Abt Hämatoiogie und internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena</s1><s2>Jena</s2><s3>DEU</s3><sZ>2 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Universitätsklinikum 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"><inist:fA14 i1="03"><s1>Molecular Pathology, SA Pathology, Adelaide, Australia and School of Medicine, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>3 aut.</sZ></inist:fA14><country>Australie</country><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"><inist:fA14 i1="04"><s1>III Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>4 aut.</sZ></inist:fA14><country>Allemagne</country><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"><inist:fA14 i1="05"><s1>Department of Hematology, Central Hospital of Coimbra</s1><s2>Coimbra</s2><s3>PRT</s3><sZ>5 aut.</sZ></inist:fA14><country>Portugal</country><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"><inist:fA14 i1="06"><s1>Haematology Department, Hammersmith Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>6 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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. 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Larson</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>University of Chicago</s1><s2>Chicago, IL</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>University of Chicago</wicri:noRegion></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"><inist:fA14 i1="10"><s1>Newcastle University Medical School</s1><s2>Newcastle</s2><s3>GBR</s3><sZ>10 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Newcastle University Medical School</wicri:noRegion></affiliation></author><author><name sortKey="Rudoltz, Marc S" sort="Rudoltz, Marc S" uniqKey="Rudoltz M" first="Marc S." last="Rudoltz">Marc S. 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Hughes</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Haematology, SA Pathology, Royal Adelaide Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>1 aut.</sZ></inist:fA14><country>Australie</country><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"><inist:fA14 i1="02"><s1>Abt Hämatoiogie und internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena</s1><s2>Jena</s2><s3>DEU</s3><sZ>2 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Universitätsklinikum 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"><inist:fA14 i1="03"><s1>Molecular Pathology, SA Pathology, Adelaide, Australia and School of Medicine, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>3 aut.</sZ></inist:fA14><country>Australie</country><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"><inist:fA14 i1="04"><s1>III Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>4 aut.</sZ></inist:fA14><country>Allemagne</country><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"><inist:fA14 i1="05"><s1>Department of Hematology, Central Hospital of Coimbra</s1><s2>Coimbra</s2><s3>PRT</s3><sZ>5 aut.</sZ></inist:fA14><country>Portugal</country><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"><inist:fA14 i1="06"><s1>Haematology Department, Hammersmith Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>6 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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="1"><inist:fA14 i1="07"><s1>Knight Cancer Institute, Oregon Health & Science University</s1><s2>Portland, OR</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Portland, OR</wicri:noRegion></affiliation></author><author><name sortKey="Guilhot, Francois" sort="Guilhot, Francois" uniqKey="Guilhot F" first="François" last="Guilhot">François Guilhot</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Centre d'Investigation Clinique CIC P 802, Inserm, Centre Hospitalier Universitaire de Poitiers</s1><s2>Poitiers</s2><s3>FRA</s3><sZ>8 aut.</sZ></inist:fA14><country>France</country><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="1"><inist:fA14 i1="09"><s1>University of Chicago</s1><s2>Chicago, IL</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>University of Chicago</wicri:noRegion></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"><inist:fA14 i1="10"><s1>Newcastle University Medical School</s1><s2>Newcastle</s2><s3>GBR</s3><sZ>10 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Newcastle University Medical School</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="1"><inist:fA14 i1="11"><s1>Novartis Pharmaceuticals Corporation</s1><s2>East Hanover, NJ</s2><s3>USA</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Novartis Pharmaceuticals Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Mone, Manisha" sort="Mone, Manisha" uniqKey="Mone M" first="Manisha" last="Mone">Manisha Mone</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Novartis Pharmaceuticals Corporation</s1><s2>East Hanover, NJ</s2><s3>USA</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Novartis Pharmaceuticals Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Wehrle, Elisabeth" sort="Wehrle, Elisabeth" uniqKey="Wehrle E" first="Elisabeth" last="Wehrle">Elisabeth Wehrle</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Novartis Pharma AG</s1><s2>Basel</s2><s3>CHE</s3><sZ>13 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>Novartis Pharma AG</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="1"><inist:fA14 i1="13"><s1>Novartis Institute of Biomedical Research</s1><s2>Cambridge, MA</s2><s3>USA</s3><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Novartis Institute of Biomedical Research</wicri:noRegion></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"><inist:fA14 i1="06"><s1>Haematology Department, Hammersmith Hospital</s1><s2>London</s2><s3>GBR</s3><sZ>6 aut.</sZ><sZ>15 aut.</sZ></inist:fA14><country>Royaume-Uni</country><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="1"><inist:fA14 i1="14"><s1>Clinical Research Division, Fred Hutchinson Cancer Research Center</s1><s2>Seattle, WA</s2><s3>USA</s3><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Seattle, WA</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Blood</title><title level="j" type="abbreviated">Blood</title><idno type="ISSN">0006-4971</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Blood</title><title level="j" type="abbreviated">Blood</title><idno type="ISSN">0006-4971</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term><term>Chronic myelogenous leukemia</term><term>Early</term><term>Early stage</term><term>Hematology</term><term>Imatinib</term><term>Interferon</term><term>International</term><term>Iris (eye)</term><term>Long term</term><term>Prognosis</term><term>Randomization</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Imatinib</term><term>Long terme</term><term>Pronostic</term><term>Interféron</term><term>Précoce</term><term>Stade précoce</term><term>Leucémie myéloïde chronique</term><term>International</term><term>Randomisation</term><term>Iris (oeil)</term><term>Hématologie</term><term>Anticancéreux</term><term>STI 571</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 BCR-ABL transcripts overtime. 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 BCR-ABL 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: BCR-ABL (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 (P < .001). This study shows a strong association between the degree to which BCR-ABL 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.</div></front></TEI><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>Nouvelle-Aquitaine</li><li>Poitou-Charentes</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"><noRegion><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name></noRegion><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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