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Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?
Abstract Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was...
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Published in: | Biology of blood and marrow transplantation 2015-07, Vol.21 (7), p.1230-1236 |
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creator | Radujkovic, Aleksandar Guglielmi, Cesare Bergantini, Stefania Iacobelli, Simona van Biezen, Anja Milojkovic, Dragana Gratwohl, Alois Schattenberg, Antonius V.M.B Verdonck, Leo F Niederwieser, Dietger W de Witte, Theo Kröger, Nicolaus Olavarria, Eduardo |
description | Abstract Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD–free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval 50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD. |
doi_str_mv | 10.1016/j.bbmt.2015.03.012 |
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Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD–free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3+ cells ≥ 50 × 106 /kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.</description><identifier>ISSN: 1083-8791</identifier><identifier>EISSN: 1523-6536</identifier><identifier>DOI: 10.1016/j.bbmt.2015.03.012</identifier><identifier>PMID: 25797175</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Allogeneic stem cell transplantation ; Child ; Child, Preschool ; Chromosome Aberrations ; Chronic Disease ; Chronic myeloid leukemia ; Donor lymphocyte infusions ; Female ; Graft vs Host Disease - etiology ; Graft vs Host Disease - immunology ; Graft vs Host Disease - mortality ; Graft vs Host Disease - prevention & control ; Graft vs Leukemia Effect ; Graft-versus-host disease ; Graft-versus-leukemia ; Hematology, Oncology and Palliative Medicine ; Hematopoietic Stem Cell Transplantation - adverse effects ; Humans ; Immunosuppressive Agents - therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy ; Lymphocyte Transfusion ; Male ; Middle Aged ; Myeloablative Agonists - therapeutic use ; Prognosis ; Recurrence ; Relapse ; Retrospective Studies ; Sex Factors ; Siblings ; Survival Analysis ; Transplantation Conditioning ; Transplantation, Homologous ; Unrelated Donors</subject><ispartof>Biology of blood and marrow transplantation, 2015-07, Vol.21 (7), p.1230-1236</ispartof><rights>American Society for Blood and Marrow Transplantation</rights><rights>2015 American Society for Blood and Marrow Transplantation</rights><rights>Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-79bcfd6d49993d7daf692fb78ded5cdb9cb0607734aef2d17f0f32bcdab706bf3</citedby><cites>FETCH-LOGICAL-c525t-79bcfd6d49993d7daf692fb78ded5cdb9cb0607734aef2d17f0f32bcdab706bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25797175$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Radujkovic, Aleksandar</creatorcontrib><creatorcontrib>Guglielmi, Cesare</creatorcontrib><creatorcontrib>Bergantini, Stefania</creatorcontrib><creatorcontrib>Iacobelli, Simona</creatorcontrib><creatorcontrib>van Biezen, Anja</creatorcontrib><creatorcontrib>Milojkovic, Dragana</creatorcontrib><creatorcontrib>Gratwohl, Alois</creatorcontrib><creatorcontrib>Schattenberg, Antonius V.M.B</creatorcontrib><creatorcontrib>Verdonck, Leo F</creatorcontrib><creatorcontrib>Niederwieser, Dietger W</creatorcontrib><creatorcontrib>de Witte, Theo</creatorcontrib><creatorcontrib>Kröger, Nicolaus</creatorcontrib><creatorcontrib>Olavarria, Eduardo</creatorcontrib><creatorcontrib>Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation</creatorcontrib><title>Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?</title><title>Biology of blood and marrow transplantation</title><addtitle>Biol Blood Marrow Transplant</addtitle><description>Abstract Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD–free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3+ cells ≥ 50 × 106 /kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Allogeneic stem cell transplantation</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromosome Aberrations</subject><subject>Chronic Disease</subject><subject>Chronic myeloid leukemia</subject><subject>Donor lymphocyte infusions</subject><subject>Female</subject><subject>Graft vs Host Disease - etiology</subject><subject>Graft vs Host Disease - immunology</subject><subject>Graft vs Host Disease - mortality</subject><subject>Graft vs Host Disease - prevention & control</subject><subject>Graft vs Leukemia Effect</subject><subject>Graft-versus-host disease</subject><subject>Graft-versus-leukemia</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Humans</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy</subject><subject>Lymphocyte Transfusion</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myeloablative Agonists - therapeutic use</subject><subject>Prognosis</subject><subject>Recurrence</subject><subject>Relapse</subject><subject>Retrospective Studies</subject><subject>Sex Factors</subject><subject>Siblings</subject><subject>Survival Analysis</subject><subject>Transplantation Conditioning</subject><subject>Transplantation, Homologous</subject><subject>Unrelated Donors</subject><issn>1083-8791</issn><issn>1523-6536</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9ksFu1DAURSMEoqXwAyyQl2wSbGcSJwiBqim0laYC0aIuLcd-7nia2MF2KuXD-n91NKWLLljZ0rv3Su-el2XvCS4IJvWnXdF1QywoJlWBywIT-iI7JBUt87oq65fpj5syb1hLDrI3IewwxmzVtK-zA1qxlhFWHWb3J846jzbzMG6dnCOgc6unYJwNSKfBeuudNRJdzNA7o9AGplsYjEC_oRdjMPYGCR3Bo-O-dzdgIWkvIwxoDX2PrrywYeyFjSKmyM_oQszoGtAvD8rIiE59Mud34MMU8qfoaxO3bno2PXMhohMTQAT49jZ7pUUf4N3je5T9-fH9an2Wb36enq-PN7msaBVz1nZSq1qt2rYtFVNC1y3VHWsUqEqqrpUdrjFj5UqApoowjXVJO6lEx3Dd6fIo-7jPHb37O0GIfDBBps2EBTcFTuqmSa1WhCUp3UuldyF40Hz0ZhB-5gTzBRff8QUXX3BxXPKEK5k-POZP3QDqyfKPTxJ82QsgbXlnwPMgDViZ6vMgI1fO_D__6zO77E3CKfpbmCHs3ORt6o8THijH_HI5mOVeSIUxaVZ1-QDMTMBJ</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Radujkovic, Aleksandar</creator><creator>Guglielmi, Cesare</creator><creator>Bergantini, Stefania</creator><creator>Iacobelli, Simona</creator><creator>van Biezen, Anja</creator><creator>Milojkovic, Dragana</creator><creator>Gratwohl, Alois</creator><creator>Schattenberg, Antonius V.M.B</creator><creator>Verdonck, Leo F</creator><creator>Niederwieser, Dietger W</creator><creator>de Witte, Theo</creator><creator>Kröger, Nicolaus</creator><creator>Olavarria, Eduardo</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>20150701</creationdate><title>Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?</title><author>Radujkovic, Aleksandar ; Guglielmi, Cesare ; Bergantini, Stefania ; Iacobelli, Simona ; van Biezen, Anja ; Milojkovic, Dragana ; Gratwohl, Alois ; Schattenberg, Antonius V.M.B ; Verdonck, Leo F ; Niederwieser, Dietger W ; de Witte, Theo ; Kröger, Nicolaus ; Olavarria, Eduardo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-79bcfd6d49993d7daf692fb78ded5cdb9cb0607734aef2d17f0f32bcdab706bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Allogeneic stem cell transplantation</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromosome Aberrations</topic><topic>Chronic Disease</topic><topic>Chronic myeloid leukemia</topic><topic>Donor lymphocyte infusions</topic><topic>Female</topic><topic>Graft vs Host Disease - etiology</topic><topic>Graft vs Host Disease - immunology</topic><topic>Graft vs Host Disease - mortality</topic><topic>Graft vs Host Disease - prevention & control</topic><topic>Graft vs Leukemia Effect</topic><topic>Graft-versus-host disease</topic><topic>Graft-versus-leukemia</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Humans</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy</topic><topic>Lymphocyte Transfusion</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myeloablative Agonists - therapeutic use</topic><topic>Prognosis</topic><topic>Recurrence</topic><topic>Relapse</topic><topic>Retrospective Studies</topic><topic>Sex Factors</topic><topic>Siblings</topic><topic>Survival Analysis</topic><topic>Transplantation Conditioning</topic><topic>Transplantation, Homologous</topic><topic>Unrelated Donors</topic><toplevel>online_resources</toplevel><creatorcontrib>Radujkovic, Aleksandar</creatorcontrib><creatorcontrib>Guglielmi, Cesare</creatorcontrib><creatorcontrib>Bergantini, Stefania</creatorcontrib><creatorcontrib>Iacobelli, Simona</creatorcontrib><creatorcontrib>van Biezen, Anja</creatorcontrib><creatorcontrib>Milojkovic, Dragana</creatorcontrib><creatorcontrib>Gratwohl, Alois</creatorcontrib><creatorcontrib>Schattenberg, Antonius V.M.B</creatorcontrib><creatorcontrib>Verdonck, Leo F</creatorcontrib><creatorcontrib>Niederwieser, Dietger W</creatorcontrib><creatorcontrib>de Witte, Theo</creatorcontrib><creatorcontrib>Kröger, Nicolaus</creatorcontrib><creatorcontrib>Olavarria, Eduardo</creatorcontrib><creatorcontrib>Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biology of blood and marrow transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Radujkovic, Aleksandar</au><au>Guglielmi, Cesare</au><au>Bergantini, Stefania</au><au>Iacobelli, Simona</au><au>van Biezen, Anja</au><au>Milojkovic, Dragana</au><au>Gratwohl, Alois</au><au>Schattenberg, Antonius V.M.B</au><au>Verdonck, Leo F</au><au>Niederwieser, Dietger W</au><au>de Witte, Theo</au><au>Kröger, Nicolaus</au><au>Olavarria, Eduardo</au><aucorp>Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?</atitle><jtitle>Biology of blood and marrow transplantation</jtitle><addtitle>Biol Blood Marrow Transplant</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>21</volume><issue>7</issue><spage>1230</spage><epage>1236</epage><pages>1230-1236</pages><issn>1083-8791</issn><eissn>1523-6536</eissn><abstract>Abstract Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD–free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3+ cells ≥ 50 × 106 /kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25797175</pmid><doi>10.1016/j.bbmt.2015.03.012</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Allogeneic stem cell transplantation Child Child, Preschool Chromosome Aberrations Chronic Disease Chronic myeloid leukemia Donor lymphocyte infusions Female Graft vs Host Disease - etiology Graft vs Host Disease - immunology Graft vs Host Disease - mortality Graft vs Host Disease - prevention & control Graft vs Leukemia Effect Graft-versus-host disease Graft-versus-leukemia Hematology, Oncology and Palliative Medicine Hematopoietic Stem Cell Transplantation - adverse effects Humans Immunosuppressive Agents - therapeutic use Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy Lymphocyte Transfusion Male Middle Aged Myeloablative Agonists - therapeutic use Prognosis Recurrence Relapse Retrospective Studies Sex Factors Siblings Survival Analysis Transplantation Conditioning Transplantation, Homologous Unrelated Donors |
title | Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease? |
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