Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial
Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR...
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| Veröffentlicht in: | Journal of clinical oncology 2014-05, Vol.32 (15), p.1595-1604 |
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| creator | Ribera, Josep-Maria Oriol, Albert Morgades, Mireia Montesinos, Pau Sarrà, Josep González-Campos, José Brunet, Salut Tormo, Mar Fernández-Abellán, Pascual Guàrdia, Ramon Bernal, María-Teresa Esteve, Jordi Barba, Pere Moreno, María-José Bermúdez, Arancha Cladera, Antonia Escoda, Lourdes García-Boyero, Raimundo Del Potro, Eloy Bergua, Juan Amigo, María-Luz Grande, Carlos Rabuñal, María-José Hernández-Rivas, Jesús-María Feliu, Evarist |
| description | Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation.
Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4).
Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS.
Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS. |
| doi_str_mv | 10.1200/JCO.2013.52.2425 |
| format | Article |
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Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4).
Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS.
Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.</description><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.2013.52.2425</identifier><identifier>PMID: 24752047</identifier><language>eng</language><publisher>United States</publisher><subject>Adolescent ; Adult ; Age Factors ; Consolidation Chemotherapy - adverse effects ; Consolidation Chemotherapy - mortality ; Disease-Free Survival ; Female ; Flow Cytometry ; Genetic Predisposition to Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Maintenance Chemotherapy ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm, Residual ; Patient Selection ; Phenotype ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Predictive Value of Tests ; Proportional Hazards Models ; Risk Factors ; Spain ; Time Factors ; Treatment Outcome ; Young Adult</subject><ispartof>Journal of clinical oncology, 2014-05, Vol.32 (15), p.1595-1604</ispartof><rights>2014 by American Society of Clinical Oncology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-47471b26adfa39306e2aa13b90fbb3e9b782f4abde4970a86cf76fb02f245c593</citedby><cites>FETCH-LOGICAL-c365t-47471b26adfa39306e2aa13b90fbb3e9b782f4abde4970a86cf76fb02f245c593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3716,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24752047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ribera, Josep-Maria</creatorcontrib><creatorcontrib>Oriol, Albert</creatorcontrib><creatorcontrib>Morgades, Mireia</creatorcontrib><creatorcontrib>Montesinos, Pau</creatorcontrib><creatorcontrib>Sarrà, Josep</creatorcontrib><creatorcontrib>González-Campos, José</creatorcontrib><creatorcontrib>Brunet, Salut</creatorcontrib><creatorcontrib>Tormo, Mar</creatorcontrib><creatorcontrib>Fernández-Abellán, Pascual</creatorcontrib><creatorcontrib>Guàrdia, Ramon</creatorcontrib><creatorcontrib>Bernal, María-Teresa</creatorcontrib><creatorcontrib>Esteve, Jordi</creatorcontrib><creatorcontrib>Barba, Pere</creatorcontrib><creatorcontrib>Moreno, María-José</creatorcontrib><creatorcontrib>Bermúdez, Arancha</creatorcontrib><creatorcontrib>Cladera, Antonia</creatorcontrib><creatorcontrib>Escoda, Lourdes</creatorcontrib><creatorcontrib>García-Boyero, Raimundo</creatorcontrib><creatorcontrib>Del Potro, Eloy</creatorcontrib><creatorcontrib>Bergua, Juan</creatorcontrib><creatorcontrib>Amigo, María-Luz</creatorcontrib><creatorcontrib>Grande, Carlos</creatorcontrib><creatorcontrib>Rabuñal, María-José</creatorcontrib><creatorcontrib>Hernández-Rivas, Jesús-María</creatorcontrib><creatorcontrib>Feliu, Evarist</creatorcontrib><title>Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation.
Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4).
Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS.
Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Consolidation Chemotherapy - adverse effects</subject><subject>Consolidation Chemotherapy - mortality</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Genetic Predisposition to Disease</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Logistic Models</subject><subject>Maintenance Chemotherapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neoplasm, Residual</subject><subject>Patient Selection</subject><subject>Phenotype</subject><subject>Philadelphia Chromosome</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Predictive Value of Tests</subject><subject>Proportional Hazards Models</subject><subject>Risk Factors</subject><subject>Spain</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9Uk2P0zAQDQjElgXOnJCPXFL8EccNt6oqLKhoV6hI3CLHGTdmnThrO6D8e5x2QbLkGfu95_HMy7K3BK8JxfjD193tmmLC1pyuaUH502xFOBW5EJw_y1ZYMJqTDft5lb0M4RfGpNgw_iK7ooXgFBdi9eTN0YOMPQwROY06c-pyb8I9uuuMlS3YsTMSqc673gXXQz7ASUbzG5BUUwRk537sXGNliEYhC9M99IlgBiRbZyGoJByQHNqUT3YJlXK-NcMJRYdAejsjNUdn3SnxPYTRDQHOhN4Mppd2OTTtlILWBJDLpY7gkUpAZ02bqnHptRAgrRY1M9LW_TmL9hD9_BFpM1xkzgWkX8YO0N3-eLP_tkXbwyHffs8xQ9EbaV9lz7W0AV4_7tfZj0_74-4mP9x-_rLbHnLFSh7zQhSCNLSUrZasYrgEKiVhTYV10zCoGrGhupBNC0UlsNyUSotSN5hqWnDFK3advb_ojt49TBBi3ZvULGvlAG4KdZpiSeimIkWC4gtUeReCB12PPjXGzzXB9eKCOrmgXlxQc1ovLkiUd4_qU9ND-5_wb-zsLxvJtAU</recordid><startdate>20140520</startdate><enddate>20140520</enddate><creator>Ribera, Josep-Maria</creator><creator>Oriol, Albert</creator><creator>Morgades, Mireia</creator><creator>Montesinos, Pau</creator><creator>Sarrà, Josep</creator><creator>González-Campos, José</creator><creator>Brunet, Salut</creator><creator>Tormo, Mar</creator><creator>Fernández-Abellán, Pascual</creator><creator>Guàrdia, Ramon</creator><creator>Bernal, María-Teresa</creator><creator>Esteve, Jordi</creator><creator>Barba, Pere</creator><creator>Moreno, María-José</creator><creator>Bermúdez, Arancha</creator><creator>Cladera, Antonia</creator><creator>Escoda, Lourdes</creator><creator>García-Boyero, Raimundo</creator><creator>Del Potro, Eloy</creator><creator>Bergua, Juan</creator><creator>Amigo, María-Luz</creator><creator>Grande, Carlos</creator><creator>Rabuñal, María-José</creator><creator>Hernández-Rivas, Jesús-María</creator><creator>Feliu, Evarist</creator><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>7X8</scope></search><sort><creationdate>20140520</creationdate><title>Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial</title><author>Ribera, Josep-Maria ; Oriol, Albert ; Morgades, Mireia ; Montesinos, Pau ; Sarrà, Josep ; González-Campos, José ; Brunet, Salut ; Tormo, Mar ; Fernández-Abellán, Pascual ; Guàrdia, Ramon ; Bernal, María-Teresa ; Esteve, Jordi ; Barba, Pere ; Moreno, María-José ; Bermúdez, Arancha ; Cladera, Antonia ; Escoda, Lourdes ; García-Boyero, Raimundo ; Del Potro, Eloy ; Bergua, Juan ; Amigo, María-Luz ; Grande, Carlos ; Rabuñal, María-José ; Hernández-Rivas, Jesús-María ; Feliu, Evarist</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-47471b26adfa39306e2aa13b90fbb3e9b782f4abde4970a86cf76fb02f245c593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age Factors</topic><topic>Consolidation Chemotherapy - 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Academic</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ribera, Josep-Maria</au><au>Oriol, Albert</au><au>Morgades, Mireia</au><au>Montesinos, Pau</au><au>Sarrà, Josep</au><au>González-Campos, José</au><au>Brunet, Salut</au><au>Tormo, Mar</au><au>Fernández-Abellán, Pascual</au><au>Guàrdia, Ramon</au><au>Bernal, María-Teresa</au><au>Esteve, Jordi</au><au>Barba, Pere</au><au>Moreno, María-José</au><au>Bermúdez, Arancha</au><au>Cladera, Antonia</au><au>Escoda, Lourdes</au><au>García-Boyero, Raimundo</au><au>Del Potro, Eloy</au><au>Bergua, Juan</au><au>Amigo, María-Luz</au><au>Grande, Carlos</au><au>Rabuñal, María-José</au><au>Hernández-Rivas, Jesús-María</au><au>Feliu, Evarist</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2014-05-20</date><risdate>2014</risdate><volume>32</volume><issue>15</issue><spage>1595</spage><epage>1604</epage><pages>1595-1604</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation.
Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4).
Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS.
Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.</abstract><cop>United States</cop><pmid>24752047</pmid><doi>10.1200/JCO.2013.52.2425</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0732-183X |
| ispartof | Journal of clinical oncology, 2014-05, Vol.32 (15), p.1595-1604 |
| issn | 0732-183X 1527-7755 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1526128914 |
| source | MEDLINE; American Society of Clinical Oncology Online Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Age Factors Consolidation Chemotherapy - adverse effects Consolidation Chemotherapy - mortality Disease-Free Survival Female Flow Cytometry Genetic Predisposition to Disease Hematopoietic Stem Cell Transplantation Humans Kaplan-Meier Estimate Logistic Models Maintenance Chemotherapy Male Middle Aged Multivariate Analysis Neoplasm, Residual Patient Selection Phenotype Philadelphia Chromosome Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Predictive Value of Tests Proportional Hazards Models Risk Factors Spain Time Factors Treatment Outcome Young Adult |
| title | Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T22%3A45%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Treatment%20of%20high-risk%20Philadelphia%20chromosome-negative%20acute%20lymphoblastic%20leukemia%20in%20adolescents%20and%20adults%20according%20to%20early%20cytologic%20response%20and%20minimal%20residual%20disease%20after%20consolidation%20assessed%20by%20flow%20cytometry:%20final%20results%20of%20the%20PETHEMA%20ALL-AR-03%20trial&rft.jtitle=Journal%20of%20clinical%20oncology&rft.au=Ribera,%20Josep-Maria&rft.date=2014-05-20&rft.volume=32&rft.issue=15&rft.spage=1595&rft.epage=1604&rft.pages=1595-1604&rft.issn=0732-183X&rft.eissn=1527-7755&rft_id=info:doi/10.1200/JCO.2013.52.2425&rft_dat=%3Cproquest_cross%3E1526128914%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1526128914&rft_id=info:pmid/24752047&rfr_iscdi=true |