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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
Main Authors: 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
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container_title Biology of blood and marrow transplantation
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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.
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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 &lt; .001). Chronic GVHD before DLI and an interval &lt;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. 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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 &lt; .001). Chronic GVHD before DLI and an interval &lt;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. 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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 &amp; 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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 &lt; .001). Chronic GVHD before DLI and an interval &lt;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 (&gt;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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