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Dose Intensification of Daunorubicin and Cytarabine During Treatment of Adult Acute Lymphoblastic Leukemia: Results of Cancer and Leukemia Group B Study 19802
Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high-dose systemic and intrathecal methotrexate could replac...
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| Published in: | Cancer 2013-01, Vol.119 (1), p.90-98 |
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| creator | STOCK, Wendy JOHNSON, Jeffrey L MCDONNELL, Diane MROZEK, Krzysztof BLOOMFIELD, Clara D LARSON, Richard A STONE, Richard M KOLITZ, Jonathan E POWELL, Bayard L WETZLER, Meir WESTERVELT, Peter MARCUCCI, Guido DEANGELO, Daniel J VARDIMAN, James W |
| description | Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high-dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis.
One hundred sixty-one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged ≥60 years.
One hundred twenty-eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow-up of 10.4 years for surviving patients, the 5-year DFS rate was 25% (95% confidence interval, 18%-33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%-37%). Patients aged |
| doi_str_mv | 10.1002/cncr.27617 |
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One hundred sixty-one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged ≥60 years.
One hundred twenty-eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow-up of 10.4 years for surviving patients, the 5-year DFS rate was 25% (95% confidence interval, 18%-33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%-37%). Patients aged <60 years who received the 80 mg/m(2) dose of daunorubicin had a DFS of 33% (95% confidence interval, 22%-44%) and an OS of 39% (95% confidence interval, 29%-49%) at 5 years. Eighty-four patients (52%) relapsed, including 9 patients (6%) who had isolated CNS relapses. The omission of cranial irradiation did not result in higher than historic CNS relapse rates.
Intensive systemic, oral, and intrathecal methotrexate dosing permitted the omission of CNS irradiation in adult patients with ALL. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historic CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.27617</identifier><identifier>PMID: 22744771</identifier><identifier>CODEN: CANCAR</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley-Blackwell</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Central Nervous System Neoplasms - prevention & control ; Combined Modality Therapy ; Cytarabine - administration & dosage ; Daunorubicin - administration & dosage ; Disease-Free Survival ; Female ; Hematologic and hematopoietic diseases ; Humans ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Methotrexate - administration & dosage ; Middle Aged ; Neoplasm Metastasis - prevention & control ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - radiotherapy ; Remission Induction ; Survival Rate ; Tumors ; Young Adult</subject><ispartof>Cancer, 2013-01, Vol.119 (1), p.90-98</ispartof><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 American Cancer Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c331t-405cfb4aa1816cd548b3c65c1b99b749a7d715375cdc38e5151a93a9ad3b88db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26898615$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22744771$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>STOCK, Wendy</creatorcontrib><creatorcontrib>JOHNSON, Jeffrey L</creatorcontrib><creatorcontrib>MCDONNELL, Diane</creatorcontrib><creatorcontrib>MROZEK, Krzysztof</creatorcontrib><creatorcontrib>BLOOMFIELD, Clara D</creatorcontrib><creatorcontrib>LARSON, Richard A</creatorcontrib><creatorcontrib>STONE, Richard M</creatorcontrib><creatorcontrib>KOLITZ, Jonathan E</creatorcontrib><creatorcontrib>POWELL, Bayard L</creatorcontrib><creatorcontrib>WETZLER, Meir</creatorcontrib><creatorcontrib>WESTERVELT, Peter</creatorcontrib><creatorcontrib>MARCUCCI, Guido</creatorcontrib><creatorcontrib>DEANGELO, Daniel J</creatorcontrib><creatorcontrib>VARDIMAN, James W</creatorcontrib><title>Dose Intensification of Daunorubicin and Cytarabine During Treatment of Adult Acute Lymphoblastic Leukemia: Results of Cancer and Leukemia Group B Study 19802</title><title>Cancer</title><addtitle>Cancer</addtitle><description>Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high-dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis.
One hundred sixty-one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged ≥60 years.
One hundred twenty-eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow-up of 10.4 years for surviving patients, the 5-year DFS rate was 25% (95% confidence interval, 18%-33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%-37%). Patients aged <60 years who received the 80 mg/m(2) dose of daunorubicin had a DFS of 33% (95% confidence interval, 22%-44%) and an OS of 39% (95% confidence interval, 29%-49%) at 5 years. Eighty-four patients (52%) relapsed, including 9 patients (6%) who had isolated CNS relapses. The omission of cranial irradiation did not result in higher than historic CNS relapse rates.
Intensive systemic, oral, and intrathecal methotrexate dosing permitted the omission of CNS irradiation in adult patients with ALL. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historic CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Central Nervous System Neoplasms - prevention & control</subject><subject>Combined Modality Therapy</subject><subject>Cytarabine - administration & dosage</subject><subject>Daunorubicin - administration & dosage</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methotrexate - administration & dosage</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis - prevention & control</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - radiotherapy</subject><subject>Remission Induction</subject><subject>Survival Rate</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpVkdtqFEEQhhsxmDV64wNI33gjTNKnme7xQtjsxhhYEDSCd0N1T0_SOtO99EHYl_FZM5uTyVVR1Fd_8deP0DtKjikh7MR4E4-ZbKh8gRaUtLIiVLCXaEEIUVUt-K9D9Dql33MrWc1foUPGpBBS0gX6tw7J4gufrU9ucAayCx6HAa-h-BCLdsZ5DL7Hq12GCNp5i9clOn-FL6OFPFmf9_yyL2PGS1OyxZvdtL0OeoSUncEbW_7YycEn_N2mGUp7fAXe2Hgr_DDH5zGULT7FP3Lpd5i2irA36GCAMdm39_UI_fxydrn6Wm2-nV-slpvKcE5zJUhtBi0AqKKN6WuhNDdNbahuWy1FC7KXtOayNr3hyta0ptByaKHnWqle8yP0-U53W_RkezObijB22-gmiLsugOueT7y77q7C304wRqRgs8DHOwETQ0rRDo-7lHT7lLp9St1tSjP8_um1R_Qhlhn4cA9AMjAOcf6WS_-5RrWqmQ3dAHjUnd8</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>STOCK, Wendy</creator><creator>JOHNSON, Jeffrey L</creator><creator>MCDONNELL, Diane</creator><creator>MROZEK, Krzysztof</creator><creator>BLOOMFIELD, Clara D</creator><creator>LARSON, Richard A</creator><creator>STONE, Richard M</creator><creator>KOLITZ, Jonathan E</creator><creator>POWELL, Bayard L</creator><creator>WETZLER, Meir</creator><creator>WESTERVELT, Peter</creator><creator>MARCUCCI, Guido</creator><creator>DEANGELO, Daniel J</creator><creator>VARDIMAN, James W</creator><general>Wiley-Blackwell</general><scope>IQODW</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>5PM</scope></search><sort><creationdate>20130101</creationdate><title>Dose Intensification of Daunorubicin and Cytarabine During Treatment of Adult Acute Lymphoblastic Leukemia: Results of Cancer and Leukemia Group B Study 19802</title><author>STOCK, Wendy ; JOHNSON, Jeffrey L ; MCDONNELL, Diane ; MROZEK, Krzysztof ; BLOOMFIELD, Clara D ; LARSON, Richard A ; STONE, Richard M ; KOLITZ, Jonathan E ; POWELL, Bayard L ; WETZLER, Meir ; WESTERVELT, Peter ; MARCUCCI, Guido ; DEANGELO, Daniel J ; VARDIMAN, James W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-405cfb4aa1816cd548b3c65c1b99b749a7d715375cdc38e5151a93a9ad3b88db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Central Nervous System Neoplasms - prevention & control</topic><topic>Combined Modality Therapy</topic><topic>Cytarabine - administration & dosage</topic><topic>Daunorubicin - administration & dosage</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methotrexate - administration & dosage</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis - prevention & control</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - radiotherapy</topic><topic>Remission Induction</topic><topic>Survival Rate</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>STOCK, Wendy</creatorcontrib><creatorcontrib>JOHNSON, Jeffrey L</creatorcontrib><creatorcontrib>MCDONNELL, Diane</creatorcontrib><creatorcontrib>MROZEK, Krzysztof</creatorcontrib><creatorcontrib>BLOOMFIELD, Clara D</creatorcontrib><creatorcontrib>LARSON, Richard A</creatorcontrib><creatorcontrib>STONE, Richard M</creatorcontrib><creatorcontrib>KOLITZ, Jonathan E</creatorcontrib><creatorcontrib>POWELL, Bayard L</creatorcontrib><creatorcontrib>WETZLER, Meir</creatorcontrib><creatorcontrib>WESTERVELT, Peter</creatorcontrib><creatorcontrib>MARCUCCI, Guido</creatorcontrib><creatorcontrib>DEANGELO, Daniel J</creatorcontrib><creatorcontrib>VARDIMAN, James W</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>PubMed Central (Full Participant titles)</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>STOCK, Wendy</au><au>JOHNSON, Jeffrey L</au><au>MCDONNELL, Diane</au><au>MROZEK, Krzysztof</au><au>BLOOMFIELD, Clara D</au><au>LARSON, Richard A</au><au>STONE, Richard M</au><au>KOLITZ, Jonathan E</au><au>POWELL, Bayard L</au><au>WETZLER, Meir</au><au>WESTERVELT, Peter</au><au>MARCUCCI, Guido</au><au>DEANGELO, Daniel J</au><au>VARDIMAN, James W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dose Intensification of Daunorubicin and Cytarabine During Treatment of Adult Acute Lymphoblastic Leukemia: Results of Cancer and Leukemia Group B Study 19802</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>119</volume><issue>1</issue><spage>90</spage><epage>98</epage><pages>90-98</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><coden>CANCAR</coden><abstract>Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high-dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis.
One hundred sixty-one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged ≥60 years.
One hundred twenty-eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow-up of 10.4 years for surviving patients, the 5-year DFS rate was 25% (95% confidence interval, 18%-33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%-37%). Patients aged <60 years who received the 80 mg/m(2) dose of daunorubicin had a DFS of 33% (95% confidence interval, 22%-44%) and an OS of 39% (95% confidence interval, 29%-49%) at 5 years. Eighty-four patients (52%) relapsed, including 9 patients (6%) who had isolated CNS relapses. The omission of cranial irradiation did not result in higher than historic CNS relapse rates.
Intensive systemic, oral, and intrathecal methotrexate dosing permitted the omission of CNS irradiation in adult patients with ALL. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historic CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets.</abstract><cop>Hoboken, NJ</cop><pub>Wiley-Blackwell</pub><pmid>22744771</pmid><doi>10.1002/cncr.27617</doi><tpages>9</tpages></addata></record> |
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| ispartof | Cancer, 2013-01, Vol.119 (1), p.90-98 |
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| subjects | Adolescent Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Central Nervous System Neoplasms - prevention & control Combined Modality Therapy Cytarabine - administration & dosage Daunorubicin - administration & dosage Disease-Free Survival Female Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Methotrexate - administration & dosage Middle Aged Neoplasm Metastasis - prevention & control Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality Precursor Cell Lymphoblastic Leukemia-Lymphoma - radiotherapy Remission Induction Survival Rate Tumors Young Adult |
| title | Dose Intensification of Daunorubicin and Cytarabine During Treatment of Adult Acute Lymphoblastic Leukemia: Results of Cancer and Leukemia Group B Study 19802 |
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