Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes

Summary Background About 50% of patients (age ≥60 years) who have acute myeloid leukaemia and are otherwise medically healthy (ie, able to undergo intensive chemotherapy) achieve a complete remission (CR) after intensive chemotherapy, but with a substantially increased risk of early death (ED) compa...

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Veröffentlicht in:The Lancet (British edition) 2010-12, Vol.376 (9757), p.2000-2008
Hauptverfasser: Krug, Utz, Dr, Röllig, Christoph, MD, Koschmieder, Anja, Heinecke, Achim, PhD, Sauerland, Maria Cristina, MSc, Schaich, Markus, Prof, Thiede, Christian, Prof, Kramer, Michael, Braess, Jan, Prof, Spiekermann, Karsten, MD, Haferlach, Torsten, Prof, Haferlach, Claudia, MD, Koschmieder, Steffen, MD, Rohde, Christian, PhD, Serve, Hubert, Prof, Wörmann, Bernhard, Prof, Hiddemann, Wolfgang, Prof, Ehninger, Gerhard, Prof, Berdel, Wolfgang E, Prof, Büchner, Thomas, Prof, Müller-Tidow, Carsten, Prof
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container_end_page 2008
container_issue 9757
container_start_page 2000
container_title The Lancet (British edition)
container_volume 376
creator Krug, Utz, Dr
Röllig, Christoph, MD
Koschmieder, Anja
Heinecke, Achim, PhD
Sauerland, Maria Cristina, MSc
Schaich, Markus, Prof
Thiede, Christian, Prof
Kramer, Michael
Braess, Jan, Prof
Spiekermann, Karsten, MD
Haferlach, Torsten, Prof
Haferlach, Claudia, MD
Koschmieder, Steffen, MD
Rohde, Christian, PhD
Serve, Hubert, Prof
Wörmann, Bernhard, Prof
Hiddemann, Wolfgang, Prof
Ehninger, Gerhard, Prof
Berdel, Wolfgang E, Prof
Büchner, Thomas, Prof
Müller-Tidow, Carsten, Prof
description Summary Background About 50% of patients (age ≥60 years) who have acute myeloid leukaemia and are otherwise medically healthy (ie, able to undergo intensive chemotherapy) achieve a complete remission (CR) after intensive chemotherapy, but with a substantially increased risk of early death (ED) compared with younger patients. We verified the association of standard clinical and laboratory variables with CR and ED and developed a web-based application for risk assessment of intensive chemotherapy in these patients. Methods Multivariate regression analysis was used to develop risk scores with or without knowledge of the cytogenetic and molecular risk profiles for a cohort of 1406 patients (aged ≥60 years) with acute myeloid leukaemia, but otherwise medically healthy, who were treated with two courses of intensive induction chemotherapy (tioguanine, standard-dose cytarabine, and daunorubicin followed by high-dose cytarabine and mitoxantrone; or with high-dose cytarabine and mitoxantrone in the first and second induction courses) in the German Acute Myeloid Leukaemia Cooperative Group 1999 study. Risk prediction was validated in an independent cohort of 801 patients (aged >60 years) with acute myeloid leukaemia who were given two courses of cytarabine and daunorubicin in the Acute Myeloid Leukaemia 1996 study. Findings Body temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2, from 7% to 61%). Interpretation The scores for acute myeloid leukaemia can be used to predict the probability of CR and the risk of ED in older patients with acute myeloid leukaemia, but otherwise medically healthy, for whom intensive induction chemotherapy is planned. This information can help physicians with difficult decisions for treatment of these patients. Funding Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft.
doi_str_mv 10.1016/S0140-6736(10)62105-8
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We verified the association of standard clinical and laboratory variables with CR and ED and developed a web-based application for risk assessment of intensive chemotherapy in these patients. Methods Multivariate regression analysis was used to develop risk scores with or without knowledge of the cytogenetic and molecular risk profiles for a cohort of 1406 patients (aged ≥60 years) with acute myeloid leukaemia, but otherwise medically healthy, who were treated with two courses of intensive induction chemotherapy (tioguanine, standard-dose cytarabine, and daunorubicin followed by high-dose cytarabine and mitoxantrone; or with high-dose cytarabine and mitoxantrone in the first and second induction courses) in the German Acute Myeloid Leukaemia Cooperative Group 1999 study. Risk prediction was validated in an independent cohort of 801 patients (aged &gt;60 years) with acute myeloid leukaemia who were given two courses of cytarabine and daunorubicin in the Acute Myeloid Leukaemia 1996 study. Findings Body temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2, from 7% to 61%). Interpretation The scores for acute myeloid leukaemia can be used to predict the probability of CR and the risk of ED in older patients with acute myeloid leukaemia, but otherwise medically healthy, for whom intensive induction chemotherapy is planned. This information can help physicians with difficult decisions for treatment of these patients. Funding Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(10)62105-8</identifier><identifier>PMID: 21131036</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Body temperature ; Bone marrow ; Chemotherapy ; Conferences ; Cytarabine - administration &amp; dosage ; Daunorubicin - administration &amp; dosage ; Female ; General aspects ; Germany ; Hematologic and hematopoietic diseases ; Humans ; Internal Medicine ; Internet ; Leukemia ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - mortality ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Meetings ; Middle Aged ; Mitoxantrone - administration &amp; dosage ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Public speaking ; Regression Analysis ; Remission Induction ; Risk Assessment ; Risk Factors ; Studies ; Surveys and Questionnaires ; Time Factors ; Transplants &amp; implants</subject><ispartof>The Lancet (British edition), 2010-12, Vol.376 (9757), p.2000-2008</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier Ltd. 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We verified the association of standard clinical and laboratory variables with CR and ED and developed a web-based application for risk assessment of intensive chemotherapy in these patients. Methods Multivariate regression analysis was used to develop risk scores with or without knowledge of the cytogenetic and molecular risk profiles for a cohort of 1406 patients (aged ≥60 years) with acute myeloid leukaemia, but otherwise medically healthy, who were treated with two courses of intensive induction chemotherapy (tioguanine, standard-dose cytarabine, and daunorubicin followed by high-dose cytarabine and mitoxantrone; or with high-dose cytarabine and mitoxantrone in the first and second induction courses) in the German Acute Myeloid Leukaemia Cooperative Group 1999 study. Risk prediction was validated in an independent cohort of 801 patients (aged &gt;60 years) with acute myeloid leukaemia who were given two courses of cytarabine and daunorubicin in the Acute Myeloid Leukaemia 1996 study. Findings Body temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2, from 7% to 61%). Interpretation The scores for acute myeloid leukaemia can be used to predict the probability of CR and the risk of ED in older patients with acute myeloid leukaemia, but otherwise medically healthy, for whom intensive induction chemotherapy is planned. This information can help physicians with difficult decisions for treatment of these patients. Funding Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Body temperature</subject><subject>Bone marrow</subject><subject>Chemotherapy</subject><subject>Conferences</subject><subject>Cytarabine - administration &amp; dosage</subject><subject>Daunorubicin - administration &amp; dosage</subject><subject>Female</subject><subject>General aspects</subject><subject>Germany</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Internet</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Leukemia, Myeloid, Acute - mortality</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. 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Röllig, Christoph, MD ; Koschmieder, Anja ; Heinecke, Achim, PhD ; Sauerland, Maria Cristina, MSc ; Schaich, Markus, Prof ; Thiede, Christian, Prof ; Kramer, Michael ; Braess, Jan, Prof ; Spiekermann, Karsten, MD ; Haferlach, Torsten, Prof ; Haferlach, Claudia, MD ; Koschmieder, Steffen, MD ; Rohde, Christian, PhD ; Serve, Hubert, Prof ; Wörmann, Bernhard, Prof ; Hiddemann, Wolfgang, Prof ; Ehninger, Gerhard, Prof ; Berdel, Wolfgang E, Prof ; Büchner, Thomas, Prof ; Müller-Tidow, Carsten, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c476t-27a27279ed97c77a27477ff0ad7bbf75b05b9c10de283ee536358c57e5de14c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Body temperature</topic><topic>Bone marrow</topic><topic>Chemotherapy</topic><topic>Conferences</topic><topic>Cytarabine - administration &amp; 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Meetings</topic><topic>Middle Aged</topic><topic>Mitoxantrone - administration &amp; dosage</topic><topic>Multivariate Analysis</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Public speaking</topic><topic>Regression Analysis</topic><topic>Remission Induction</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Studies</topic><topic>Surveys and Questionnaires</topic><topic>Time Factors</topic><topic>Transplants &amp; implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krug, Utz, Dr</creatorcontrib><creatorcontrib>Röllig, Christoph, MD</creatorcontrib><creatorcontrib>Koschmieder, Anja</creatorcontrib><creatorcontrib>Heinecke, Achim, PhD</creatorcontrib><creatorcontrib>Sauerland, Maria Cristina, MSc</creatorcontrib><creatorcontrib>Schaich, Markus, Prof</creatorcontrib><creatorcontrib>Thiede, Christian, Prof</creatorcontrib><creatorcontrib>Kramer, Michael</creatorcontrib><creatorcontrib>Braess, Jan, Prof</creatorcontrib><creatorcontrib>Spiekermann, Karsten, MD</creatorcontrib><creatorcontrib>Haferlach, Torsten, Prof</creatorcontrib><creatorcontrib>Haferlach, Claudia, MD</creatorcontrib><creatorcontrib>Koschmieder, Steffen, MD</creatorcontrib><creatorcontrib>Rohde, Christian, PhD</creatorcontrib><creatorcontrib>Serve, Hubert, Prof</creatorcontrib><creatorcontrib>Wörmann, Bernhard, Prof</creatorcontrib><creatorcontrib>Hiddemann, Wolfgang, Prof</creatorcontrib><creatorcontrib>Ehninger, Gerhard, Prof</creatorcontrib><creatorcontrib>Berdel, Wolfgang E, Prof</creatorcontrib><creatorcontrib>Büchner, Thomas, Prof</creatorcontrib><creatorcontrib>Müller-Tidow, Carsten, Prof</creatorcontrib><creatorcontrib>for the German Acute Myeloid Leukaemia Cooperative Group and the Study Alliance Leukemia Investigators</creatorcontrib><creatorcontrib>Study Alliance Leukemia Investigators</creatorcontrib><creatorcontrib>German Acute Myeloid Leukaemia Cooperative Group</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>News PRO</collection><collection>Pharma and Biotech Premium PRO</collection><collection>Global News &amp; ABI/Inform Professional</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</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>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Newsstand Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing &amp; Allied Health Premium</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 One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krug, Utz, Dr</au><au>Röllig, Christoph, MD</au><au>Koschmieder, Anja</au><au>Heinecke, Achim, PhD</au><au>Sauerland, Maria Cristina, MSc</au><au>Schaich, Markus, Prof</au><au>Thiede, Christian, Prof</au><au>Kramer, Michael</au><au>Braess, Jan, Prof</au><au>Spiekermann, Karsten, MD</au><au>Haferlach, Torsten, Prof</au><au>Haferlach, Claudia, MD</au><au>Koschmieder, Steffen, MD</au><au>Rohde, Christian, PhD</au><au>Serve, Hubert, Prof</au><au>Wörmann, Bernhard, Prof</au><au>Hiddemann, Wolfgang, Prof</au><au>Ehninger, Gerhard, Prof</au><au>Berdel, Wolfgang E, Prof</au><au>Büchner, Thomas, Prof</au><au>Müller-Tidow, Carsten, Prof</au><aucorp>for the German Acute Myeloid Leukaemia Cooperative Group and the Study Alliance Leukemia Investigators</aucorp><aucorp>Study Alliance Leukemia Investigators</aucorp><aucorp>German Acute Myeloid Leukaemia Cooperative Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2010-12-11</date><risdate>2010</risdate><volume>376</volume><issue>9757</issue><spage>2000</spage><epage>2008</epage><pages>2000-2008</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Summary Background About 50% of patients (age ≥60 years) who have acute myeloid leukaemia and are otherwise medically healthy (ie, able to undergo intensive chemotherapy) achieve a complete remission (CR) after intensive chemotherapy, but with a substantially increased risk of early death (ED) compared with younger patients. We verified the association of standard clinical and laboratory variables with CR and ED and developed a web-based application for risk assessment of intensive chemotherapy in these patients. Methods Multivariate regression analysis was used to develop risk scores with or without knowledge of the cytogenetic and molecular risk profiles for a cohort of 1406 patients (aged ≥60 years) with acute myeloid leukaemia, but otherwise medically healthy, who were treated with two courses of intensive induction chemotherapy (tioguanine, standard-dose cytarabine, and daunorubicin followed by high-dose cytarabine and mitoxantrone; or with high-dose cytarabine and mitoxantrone in the first and second induction courses) in the German Acute Myeloid Leukaemia Cooperative Group 1999 study. Risk prediction was validated in an independent cohort of 801 patients (aged &gt;60 years) with acute myeloid leukaemia who were given two courses of cytarabine and daunorubicin in the Acute Myeloid Leukaemia 1996 study. Findings Body temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2, from 7% to 61%). Interpretation The scores for acute myeloid leukaemia can be used to predict the probability of CR and the risk of ED in older patients with acute myeloid leukaemia, but otherwise medically healthy, for whom intensive induction chemotherapy is planned. This information can help physicians with difficult decisions for treatment of these patients. Funding Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>21131036</pmid><doi>10.1016/S0140-6736(10)62105-8</doi><tpages>9</tpages></addata></record>
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identifier ISSN: 0140-6736
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issn 0140-6736
1474-547X
language eng
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source MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland
subjects Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Body temperature
Bone marrow
Chemotherapy
Conferences
Cytarabine - administration & dosage
Daunorubicin - administration & dosage
Female
General aspects
Germany
Hematologic and hematopoietic diseases
Humans
Internal Medicine
Internet
Leukemia
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - mortality
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Meetings
Middle Aged
Mitoxantrone - administration & dosage
Multivariate Analysis
Predictive Value of Tests
Prognosis
Public speaking
Regression Analysis
Remission Induction
Risk Assessment
Risk Factors
Studies
Surveys and Questionnaires
Time Factors
Transplants & implants
title Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes
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