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Upfront Consolidation Combining Yttrium-90 Ibritumomab Tiuxetan and High-Dose Therapy with Stem Cell Transplantation in Poor-Risk Patients with Diffuse Large B Cell Lymphoma

Abstract We evaluated the safety and efficacy of standard-dose yttrium-90 (Y90 ) ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma (DLBCL) (clin...

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Published in:Biology of blood and marrow transplantation 2014-12, Vol.20 (12), p.1905-1911
Main Authors: Fruchart, Christophe, Tilly, Hervé, Morschhauser, Franck, Ghesquières, Hervé, Bouteloup, Marie, Fermé, Christophe, Van Den Neste, Eric, Bordessoule, Dominique, Bouabdallah, Reda, Delmer, Alain, Casasnovas, René Olivier, Ysebaert, Loïc, Ciappuccini, Renaud, Briere, Josette, Gisselbrecht, Christian
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container_issue 12
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container_title Biology of blood and marrow transplantation
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creator Fruchart, Christophe
Tilly, Hervé
Morschhauser, Franck
Ghesquières, Hervé
Bouteloup, Marie
Fermé, Christophe
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Bordessoule, Dominique
Bouabdallah, Reda
Delmer, Alain
Casasnovas, René Olivier
Ysebaert, Loïc
Ciappuccini, Renaud
Briere, Josette
Gisselbrecht, Christian
description Abstract We evaluated the safety and efficacy of standard-dose yttrium-90 (Y90 ) ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma (DLBCL) (clinicaltrials.gov: NCT00689169 ). Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y90 ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of >500/μL and platelet count of >20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus >2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y90 ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. First-line consolidation with Y90 ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET status after induction treatment and warrants a randomized study.
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Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y90 ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of &gt;500/μL and platelet count of &gt;20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus &gt;2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y90 ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. First-line consolidation with Y90 ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET status after induction treatment and warrants a randomized study.</description><identifier>ISSN: 1083-8791</identifier><identifier>EISSN: 1523-6536</identifier><identifier>DOI: 10.1016/j.bbmt.2014.07.024</identifier><identifier>PMID: 25072780</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject><![CDATA[90Y-ibritumomab tiuxetan ; Adolescent ; Adult ; Aged ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal, Murine-Derived - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Autografts ; BEAM regimen ; Carmustine - administration & dosage ; Consolidation Chemotherapy ; Cytarabine - administration & dosage ; Diffuse large B cell lymphoma (DLBCL) ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hematology, Oncology and Palliative Medicine ; Humans ; Lymphoma, Large B-Cell, Diffuse - mortality ; Lymphoma, Large B-Cell, Diffuse - therapy ; Male ; Melphalan - administration & dosage ; Middle Aged ; Podophyllotoxin - administration & dosage ; Prospective Studies ; Risk Factors ; Rituximab ; Stem Cell Transplantation ; Survival Rate ; Transplantation]]></subject><ispartof>Biology of blood and marrow transplantation, 2014-12, Vol.20 (12), p.1905-1911</ispartof><rights>American Society for Blood and Marrow Transplantation</rights><rights>2014 American Society for Blood and Marrow Transplantation</rights><rights>Copyright © 2014 American Society for Blood and Marrow Transplantation. 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All rights reserved.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-b8ad764ca773431fadf809052acb2e02b2edf6e8ba81e93522de9814a75385a93</citedby><cites>FETCH-LOGICAL-c455t-b8ad764ca773431fadf809052acb2e02b2edf6e8ba81e93522de9814a75385a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25072780$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fruchart, Christophe</creatorcontrib><creatorcontrib>Tilly, Hervé</creatorcontrib><creatorcontrib>Morschhauser, Franck</creatorcontrib><creatorcontrib>Ghesquières, Hervé</creatorcontrib><creatorcontrib>Bouteloup, Marie</creatorcontrib><creatorcontrib>Fermé, Christophe</creatorcontrib><creatorcontrib>Van Den Neste, Eric</creatorcontrib><creatorcontrib>Bordessoule, Dominique</creatorcontrib><creatorcontrib>Bouabdallah, Reda</creatorcontrib><creatorcontrib>Delmer, Alain</creatorcontrib><creatorcontrib>Casasnovas, René Olivier</creatorcontrib><creatorcontrib>Ysebaert, Loïc</creatorcontrib><creatorcontrib>Ciappuccini, Renaud</creatorcontrib><creatorcontrib>Briere, Josette</creatorcontrib><creatorcontrib>Gisselbrecht, Christian</creatorcontrib><title>Upfront Consolidation Combining Yttrium-90 Ibritumomab Tiuxetan and High-Dose Therapy with Stem Cell Transplantation in Poor-Risk Patients with Diffuse Large B Cell Lymphoma</title><title>Biology of blood and marrow transplantation</title><addtitle>Biol Blood Marrow Transplant</addtitle><description>Abstract We evaluated the safety and efficacy of standard-dose yttrium-90 (Y90 ) ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma (DLBCL) (clinicaltrials.gov: NCT00689169 ). Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y90 ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of &gt;500/μL and platelet count of &gt;20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus &gt;2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y90 ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. 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dosage</subject><subject>Middle Aged</subject><subject>Podophyllotoxin - administration &amp; dosage</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Rituximab</subject><subject>Stem Cell Transplantation</subject><subject>Survival Rate</subject><subject>Transplantation</subject><issn>1083-8791</issn><issn>1523-6536</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNp9kstu1DAUhiMEohd4ARbISzYJviVOJIQEU6CVRqKiUwlWluOczHia2MF2KPNQvCMepbBgwcY3_f9v-3wny14QXBBMqtf7om3HWFBMeIFFgSl_lJ2SkrK8Kln1OK1xzfJaNOQkOwthjzEWvG6eZie0xIKKGp9mv26n3jsb0crZ4AbTqWicTbuxNdbYLfoWozfzmDcYXbXexHl0o2rRxsw_ISqLlO3Qpdnu8gsXAG124NV0QPcm7tBNhBGtYBjQxisbpkHZuMQbi66d8_kXE-7QdToDG8NiujB9P6ektfJbQO8X__owTrt077PsSa-GAM8f5vPs9uOHzeoyX3_-dLV6t841L8uYt7XqRMW1EoJxRnrV9TVucEmVbilgmoaur6BuVU2gYSWlHTQ14UqUrC5Vw86zV0vu5N33GUKUowk6vURZcHOQpKJNU3FBqiSli1R7F4KHXk7ejMofJMHyiEnu5RGTPGKSWMiEKZlePuTP7QjdX8sfLknwZhFA-uUPA14GnYqkoTMedJSdM__Pf_uPXQ8Jp1bDHRwg7N3sbaqfJDJQieXNsVGOfUI4xlywr-w3WVW7UQ</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Fruchart, Christophe</creator><creator>Tilly, Hervé</creator><creator>Morschhauser, Franck</creator><creator>Ghesquières, Hervé</creator><creator>Bouteloup, Marie</creator><creator>Fermé, Christophe</creator><creator>Van Den Neste, Eric</creator><creator>Bordessoule, Dominique</creator><creator>Bouabdallah, Reda</creator><creator>Delmer, Alain</creator><creator>Casasnovas, René Olivier</creator><creator>Ysebaert, Loïc</creator><creator>Ciappuccini, Renaud</creator><creator>Briere, Josette</creator><creator>Gisselbrecht, Christian</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20141201</creationdate><title>Upfront Consolidation Combining Yttrium-90 Ibritumomab Tiuxetan and High-Dose Therapy with Stem Cell Transplantation in Poor-Risk Patients with Diffuse Large B Cell Lymphoma</title><author>Fruchart, Christophe ; 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Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y90 ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of &gt;500/μL and platelet count of &gt;20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus &gt;2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y90 ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. First-line consolidation with Y90 ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET status after induction treatment and warrants a randomized study.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25072780</pmid><doi>10.1016/j.bbmt.2014.07.024</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1083-8791
ispartof Biology of blood and marrow transplantation, 2014-12, Vol.20 (12), p.1905-1911
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subjects 90Y-ibritumomab tiuxetan
Adolescent
Adult
Aged
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal, Murine-Derived - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Autografts
BEAM regimen
Carmustine - administration & dosage
Consolidation Chemotherapy
Cytarabine - administration & dosage
Diffuse large B cell lymphoma (DLBCL)
Disease-Free Survival
Female
Follow-Up Studies
Hematology, Oncology and Palliative Medicine
Humans
Lymphoma, Large B-Cell, Diffuse - mortality
Lymphoma, Large B-Cell, Diffuse - therapy
Male
Melphalan - administration & dosage
Middle Aged
Podophyllotoxin - administration & dosage
Prospective Studies
Risk Factors
Rituximab
Stem Cell Transplantation
Survival Rate
Transplantation
title Upfront Consolidation Combining Yttrium-90 Ibritumomab Tiuxetan and High-Dose Therapy with Stem Cell Transplantation in Poor-Risk Patients with Diffuse Large B Cell Lymphoma
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