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Impact of chronic graft-versus-host disease on late relapse and survival on 7489 patients after myeloablative allogeneic hematopoietic cell transplantation for leukemia

Identifieur interne : 001012 ( Pmc/Checkpoint ); précédent : 001011; suivant : 001013

Impact of chronic graft-versus-host disease on late relapse and survival on 7489 patients after myeloablative allogeneic hematopoietic cell transplantation for leukemia

Auteurs : Michael Boyiadzis [États-Unis] ; Mukta Arora [États-Unis] ; John P. Klein [États-Unis] ; Anna Hassebroek [États-Unis] ; Michael Hemmer [États-Unis] ; Alvaro Urbano-Ispizua ; Joseph H. Antin [États-Unis] ; Brian J. Bolwell [États-Unis] ; Jean-Yves Y. Cahn [France] ; Mitchell S. Cairo [États-Unis] ; Corey S. Cutler [États-Unis] ; Mary E. Flowers [États-Unis] ; Robert P. Gale [Royaume-Uni] ; Roger Herzig [États-Unis] ; Luis M. Isola [États-Unis] ; David A. Jacobsohn [États-Unis] ; Madan H. Jagasia [États-Unis] ; Thomas R. Klumpp [États-Unis] ; Stephanie J. Lee [États-Unis] ; Effie W. Petersdorf [États-Unis] ; Stella Santarone [Italie] ; Stephen R. Spellman [États-Unis] ; Harry C. Schouten [Pays-Bas] ; Leo F. Verdonck [Pays-Bas] ; John R. Wingard [États-Unis] ; Daniel J. Weisdorf [États-Unis] ; Mary M. Horowitz [États-Unis] ; Steven Z. Pavletic [États-Unis]

Source :

RBID : PMC:4411210

Abstract

Purpose

Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year post-transplant at the time when acute GVHD is still active.

Experimental design

The current study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7489 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) who were leukemia-free at12 months after myeloablative allogeneic HCT.

Results

Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on relapse was present only in patients with CML (RR: 0.47, 95% CI: 0.37-0.59, P <0.0001). cGVHD was significantly associated with higher risk of treatment related mortality, (RR: 2.43, 95% CI: 2.09-2.82, P <0.0001) and inferior overall survival (RR: 1.56, 95% CI: 1.41-1.73, P <0.0001) for all diseases. In patients with CML all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse.

Conclusions

These results indicate that clinically relevant anti-leukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL or MDS. Chronic GVHD in patients who are one year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival.


Url:
DOI: 10.1158/1078-0432.CCR-14-0586
PubMed: 25348512
PubMed Central: 4411210


Affiliations:


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PMC:4411210

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<name sortKey="Lee, Stephanie J" sort="Lee, Stephanie J" uniqKey="Lee S" first="Stephanie J." last="Lee">Stephanie J. Lee</name>
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<name sortKey="Bolwell, Brian J" sort="Bolwell, Brian J" uniqKey="Bolwell B" first="Brian J." last="Bolwell">Brian J. Bolwell</name>
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</author>
<author>
<name sortKey="Cairo, Mitchell S" sort="Cairo, Mitchell S" uniqKey="Cairo M" first="Mitchell S." last="Cairo">Mitchell S. Cairo</name>
<affiliation wicri:level="2">
<nlm:aff id="A9">New York Medical College, Valhalla, NY</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">État de New York</region>
</placeName>
<wicri:cityArea>New York Medical College, Valhalla</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Cutler, Corey S" sort="Cutler, Corey S" uniqKey="Cutler C" first="Corey S." last="Cutler">Corey S. Cutler</name>
<affiliation wicri:level="2">
<nlm:aff id="A6">Dana Farber Cancer Institute, Boston, MA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Dana Farber Cancer Institute, Boston</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Flowers, Mary E" sort="Flowers, Mary E" uniqKey="Flowers M" first="Mary E." last="Flowers">Mary E. Flowers</name>
<affiliation wicri:level="2">
<nlm:aff id="A10">Fred Hutchinson Cancer Research Center, Seattle, WA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Gale, Robert P" sort="Gale, Robert P" uniqKey="Gale R" first="Robert P." last="Gale">Robert P. Gale</name>
<affiliation wicri:level="3">
<nlm:aff id="A11">Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Imperial College, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Herzig, Roger" sort="Herzig, Roger" uniqKey="Herzig R" first="Roger" last="Herzig">Roger Herzig</name>
<affiliation wicri:level="2">
<nlm:aff id="A12">University of Louisville, Hospital/James Brown Cancer Center, Louisville, KY USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Kentucky</region>
</placeName>
<wicri:cityArea>University of Louisville, Hospital/James Brown Cancer Center, Louisville</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Isola, Luis M" sort="Isola, Luis M" uniqKey="Isola L" first="Luis M." last="Isola">Luis M. Isola</name>
<affiliation wicri:level="2">
<nlm:aff id="A13">Mount Sinai Medical Center, Miami, FL USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Floride</region>
</placeName>
<wicri:cityArea>Mount Sinai Medical Center, Miami</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Jacobsohn, David A" sort="Jacobsohn, David A" uniqKey="Jacobsohn D" first="David A." last="Jacobsohn">David A. Jacobsohn</name>
<affiliation wicri:level="2">
<nlm:aff id="A14">National Medical Center, Washington, DC USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">District de Columbia</region>
</placeName>
<wicri:cityArea>National Medical Center, Washington</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Jagasia, Madan H" sort="Jagasia, Madan H" uniqKey="Jagasia M" first="Madan H." last="Jagasia">Madan H. Jagasia</name>
<affiliation wicri:level="2">
<nlm:aff id="A15">Vanderbilt University Medical Center; Nashville, TN USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Vanderbilt University Medical Center; Nashville</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Klumpp, Thomas R" sort="Klumpp, Thomas R" uniqKey="Klumpp T" first="Thomas R." last="Klumpp">Thomas R. Klumpp</name>
<affiliation wicri:level="2">
<nlm:aff id="A16">Temple Bone Marrow Transplant Program, Philadelphia, PA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Temple Bone Marrow Transplant Program, Philadelphia</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Lee, Stephanie J" sort="Lee, Stephanie J" uniqKey="Lee S" first="Stephanie J." last="Lee">Stephanie J. Lee</name>
<affiliation wicri:level="2">
<nlm:aff id="A10">Fred Hutchinson Cancer Research Center, Seattle, WA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Petersdorf, Effie W" sort="Petersdorf, Effie W" uniqKey="Petersdorf E" first="Effie W." last="Petersdorf">Effie W. Petersdorf</name>
<affiliation wicri:level="2">
<nlm:aff id="A10">Fred Hutchinson Cancer Research Center, Seattle, WA USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Santarone, Stella" sort="Santarone, Stella" uniqKey="Santarone S" first="Stella" last="Santarone">Stella Santarone</name>
<affiliation wicri:level="1">
<nlm:aff id="A17">Ospedale Civile BMT Center, Pescara, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Ospedale Civile BMT Center, Pescara</wicri:regionArea>
<wicri:noRegion>Pescara</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Spellman, Stephen R" sort="Spellman, Stephen R" uniqKey="Spellman S" first="Stephen R." last="Spellman">Stephen R. Spellman</name>
<affiliation wicri:level="2">
<nlm:aff id="A4">Center for International Blood and Marrow Transplant Research, Minneapolis, MN USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Center for International Blood and Marrow Transplant Research, Minneapolis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Schouten, Harry C" sort="Schouten, Harry C" uniqKey="Schouten H" first="Harry C." last="Schouten">Harry C. Schouten</name>
<affiliation wicri:level="1">
<nlm:aff id="A18">Academische Ziekenhuis Maastricht, Maastricht, Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Academische Ziekenhuis Maastricht, Maastricht</wicri:regionArea>
<wicri:noRegion>Maastricht</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Verdonck, Leo F" sort="Verdonck, Leo F" uniqKey="Verdonck L" first="Leo F." last="Verdonck">Leo F. Verdonck</name>
<affiliation wicri:level="1">
<nlm:aff id="A19">Isala Clinics, Zwolle, Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Isala Clinics, Zwolle</wicri:regionArea>
<wicri:noRegion>Zwolle</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Wingard, John R" sort="Wingard, John R" uniqKey="Wingard J" first="John R." last="Wingard">John R. Wingard</name>
<affiliation wicri:level="2">
<nlm:aff id="A20">Shands HealthCare & University of Florida, Gainesville, FL, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Shands HealthCare & University of Florida, Gainesville, FL</wicri:regionArea>
<placeName>
<region type="state">Floride</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Weisdorf, Daniel J" sort="Weisdorf, Daniel J" uniqKey="Weisdorf D" first="Daniel J." last="Weisdorf">Daniel J. Weisdorf</name>
<affiliation wicri:level="2">
<nlm:aff id="A2">University of Minnesota Medical Center, Fairview, Minneapolis, MN USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>University of Minnesota Medical Center, Fairview, Minneapolis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Horowitz, Mary M" sort="Horowitz, Mary M" uniqKey="Horowitz M" first="Mary M." last="Horowitz">Mary M. Horowitz</name>
<affiliation wicri:level="2">
<nlm:aff id="A3">Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI USA</nlm:aff>
<country>États-Unis</country>
<placeName>
<region type="state">Wisconsin</region>
</placeName>
<wicri:cityArea>Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Pavletic, Steven Z" sort="Pavletic, Steven Z" uniqKey="Pavletic S" first="Steven Z." last="Pavletic">Steven Z. Pavletic</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">National Cancer Institute, Bethesda, MD</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
<wicri:cityArea>National Cancer Institute, Bethesda</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Clinical cancer research : an official journal of the American Association for Cancer Research</title>
<idno type="ISSN">1078-0432</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec id="S1">
<title>Purpose</title>
<p id="P1">Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year post-transplant at the time when acute GVHD is still active.</p>
</sec>
<sec id="S2">
<title>Experimental design</title>
<p id="P2">The current study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7489 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) who were leukemia-free at12 months after myeloablative allogeneic HCT.</p>
</sec>
<sec id="S3">
<title>Results</title>
<p id="P3">Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on relapse was present only in patients with CML (RR: 0.47, 95% CI: 0.37-0.59, P <0.0001). cGVHD was significantly associated with higher risk of treatment related mortality, (RR: 2.43, 95% CI: 2.09-2.82, P <0.0001) and inferior overall survival (RR: 1.56, 95% CI: 1.41-1.73, P <0.0001) for all diseases. In patients with CML all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse.</p>
</sec>
<sec id="S4">
<title>Conclusions</title>
<p id="P4">These results indicate that clinically relevant anti-leukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL or MDS. Chronic GVHD in patients who are one year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">9502500</journal-id>
<journal-id journal-id-type="pubmed-jr-id">8794</journal-id>
<journal-id journal-id-type="nlm-ta">Clin Cancer Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Clin. Cancer Res.</journal-id>
<journal-title-group>
<journal-title>Clinical cancer research : an official journal of the American Association for Cancer Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">1078-0432</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">25348512</article-id>
<article-id pub-id-type="pmc">4411210</article-id>
<article-id pub-id-type="doi">10.1158/1078-0432.CCR-14-0586</article-id>
<article-id pub-id-type="manuscript">NIHMS638601</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Impact of chronic graft-versus-host disease on late relapse and survival on 7489 patients after myeloablative allogeneic hematopoietic cell transplantation for leukemia</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Boyiadzis</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Arora</surname>
<given-names>Mukta</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Klein</surname>
<given-names>John P.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hassebroek</surname>
<given-names>Anna</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hemmer</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Urbano-Ispizua</surname>
<given-names>Alvaro</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Antin</surname>
<given-names>Joseph H.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bolwell</surname>
<given-names>Brian J.</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cahn</surname>
<given-names>Jean-Yves Y.</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cairo</surname>
<given-names>Mitchell S.</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cutler</surname>
<given-names>Corey S.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Flowers</surname>
<given-names>Mary E.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gale</surname>
<given-names>Robert P.</given-names>
</name>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Herzig</surname>
<given-names>Roger</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Isola</surname>
<given-names>Luis M.</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jacobsohn</surname>
<given-names>David A.</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jagasia</surname>
<given-names>Madan H.</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Klumpp</surname>
<given-names>Thomas R.</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lee</surname>
<given-names>Stephanie J.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Petersdorf</surname>
<given-names>Effie W.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Santarone</surname>
<given-names>Stella</given-names>
</name>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Spellman</surname>
<given-names>Stephen R.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schouten</surname>
<given-names>Harry C.</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Verdonck</surname>
<given-names>Leo F.</given-names>
</name>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wingard</surname>
<given-names>John R.</given-names>
</name>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Weisdorf</surname>
<given-names>Daniel J.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Horowitz</surname>
<given-names>Mary M.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pavletic</surname>
<given-names>Steven Z.</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
University of Pittsburgh School of Medicine, Pittsburgh, PA USA</aff>
<aff id="A2">
<label>2</label>
University of Minnesota Medical Center, Fairview, Minneapolis, MN USA</aff>
<aff id="A3">
<label>3</label>
Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI USA</aff>
<aff id="A4">
<label>4</label>
Center for International Blood and Marrow Transplant Research, Minneapolis, MN USA</aff>
<aff id="A5">
<label>5</label>
Institute of Hematology and Oncology, Hospital Clínic.</aff>
<aff id="A6">
<label>6</label>
Dana Farber Cancer Institute, Boston, MA USA</aff>
<aff id="A7">
<label>7</label>
Cleveland Clinic Foundation, Cleveland, OH USA</aff>
<aff id="A8">
<label>8</label>
Hopital Michallon, CHU de Grenoble, Grenoble, France</aff>
<aff id="A9">
<label>9</label>
New York Medical College, Valhalla, NY</aff>
<aff id="A10">
<label>10</label>
Fred Hutchinson Cancer Research Center, Seattle, WA USA</aff>
<aff id="A11">
<label>11</label>
Imperial College, London, UK</aff>
<aff id="A12">
<label>12</label>
University of Louisville, Hospital/James Brown Cancer Center, Louisville, KY USA</aff>
<aff id="A13">
<label>13</label>
Mount Sinai Medical Center, Miami, FL USA</aff>
<aff id="A14">
<label>14</label>
National Medical Center, Washington, DC USA</aff>
<aff id="A15">
<label>15</label>
Vanderbilt University Medical Center; Nashville, TN USA</aff>
<aff id="A16">
<label>16</label>
Temple Bone Marrow Transplant Program, Philadelphia, PA USA</aff>
<aff id="A17">
<label>17</label>
Ospedale Civile BMT Center, Pescara, Italy</aff>
<aff id="A18">
<label>18</label>
Academische Ziekenhuis Maastricht, Maastricht, Netherlands</aff>
<aff id="A19">
<label>19</label>
Isala Clinics, Zwolle, Netherlands</aff>
<aff id="A20">
<label>20</label>
Shands HealthCare & University of Florida, Gainesville, FL, USA</aff>
<aff id="A21">
<label>21</label>
National Cancer Institute, Bethesda, MD</aff>
<author-notes>
<corresp id="CR1">
<bold>Corresponding Author:</bold>
Michael Boyiadzis, MD, MHSc. University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Suite 572,Pittsburgh, PA 15232. Phone: 412-648-6589, Fax:412-648-6579,
<email>boyiadzism@upmc.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>9</day>
<month>1</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>27</day>
<month>10</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub">
<day>1</day>
<month>5</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>01</day>
<month>5</month>
<year>2016</year>
</pub-date>
<volume>21</volume>
<issue>9</issue>
<fpage>2020</fpage>
<lpage>2028</lpage>
<pmc-comment>elocation-id from pubmed: 10.1158/1078-0432.CCR-14-0586</pmc-comment>
<abstract>
<sec id="S1">
<title>Purpose</title>
<p id="P1">Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year post-transplant at the time when acute GVHD is still active.</p>
</sec>
<sec id="S2">
<title>Experimental design</title>
<p id="P2">The current study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7489 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) who were leukemia-free at12 months after myeloablative allogeneic HCT.</p>
</sec>
<sec id="S3">
<title>Results</title>
<p id="P3">Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on relapse was present only in patients with CML (RR: 0.47, 95% CI: 0.37-0.59, P <0.0001). cGVHD was significantly associated with higher risk of treatment related mortality, (RR: 2.43, 95% CI: 2.09-2.82, P <0.0001) and inferior overall survival (RR: 1.56, 95% CI: 1.41-1.73, P <0.0001) for all diseases. In patients with CML all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse.</p>
</sec>
<sec id="S4">
<title>Conclusions</title>
<p id="P4">These results indicate that clinically relevant anti-leukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL or MDS. Chronic GVHD in patients who are one year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival.</p>
</sec>
</abstract>
<kwd-group>
<kwd>allogeneic hematopoietic cell transplantation</kwd>
<kwd>chronic graft-versus-host disease</kwd>
<kwd>relapse</kwd>
<kwd>leukemia</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>France</li>
<li>Italie</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Auvergne-Rhône-Alpes</li>
<li>District de Columbia</li>
<li>Floride</li>
<li>Grand Londres</li>
<li>Kentucky</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Minnesota</li>
<li>Ohio</li>
<li>Pennsylvanie</li>
<li>Rhône-Alpes</li>
<li>Tennessee</li>
<li>Washington (État)</li>
<li>Wisconsin</li>
<li>État de New York</li>
</region>
<settlement>
<li>Grenoble</li>
<li>Londres</li>
</settlement>
</list>
<tree>
<noCountry>
<name sortKey="Urbano Ispizua, Alvaro" sort="Urbano Ispizua, Alvaro" uniqKey="Urbano Ispizua A" first="Alvaro" last="Urbano-Ispizua">Alvaro Urbano-Ispizua</name>
</noCountry>
<country name="États-Unis">
<region name="Pennsylvanie">
<name sortKey="Boyiadzis, Michael" sort="Boyiadzis, Michael" uniqKey="Boyiadzis M" first="Michael" last="Boyiadzis">Michael Boyiadzis</name>
</region>
<name sortKey="Antin, Joseph H" sort="Antin, Joseph H" uniqKey="Antin J" first="Joseph H." last="Antin">Joseph H. Antin</name>
<name sortKey="Arora, Mukta" sort="Arora, Mukta" uniqKey="Arora M" first="Mukta" last="Arora">Mukta Arora</name>
<name sortKey="Bolwell, Brian J" sort="Bolwell, Brian J" uniqKey="Bolwell B" first="Brian J." last="Bolwell">Brian J. Bolwell</name>
<name sortKey="Cairo, Mitchell S" sort="Cairo, Mitchell S" uniqKey="Cairo M" first="Mitchell S." last="Cairo">Mitchell S. Cairo</name>
<name sortKey="Cutler, Corey S" sort="Cutler, Corey S" uniqKey="Cutler C" first="Corey S." last="Cutler">Corey S. Cutler</name>
<name sortKey="Flowers, Mary E" sort="Flowers, Mary E" uniqKey="Flowers M" first="Mary E." last="Flowers">Mary E. Flowers</name>
<name sortKey="Hassebroek, Anna" sort="Hassebroek, Anna" uniqKey="Hassebroek A" first="Anna" last="Hassebroek">Anna Hassebroek</name>
<name sortKey="Hemmer, Michael" sort="Hemmer, Michael" uniqKey="Hemmer M" first="Michael" last="Hemmer">Michael Hemmer</name>
<name sortKey="Herzig, Roger" sort="Herzig, Roger" uniqKey="Herzig R" first="Roger" last="Herzig">Roger Herzig</name>
<name sortKey="Horowitz, Mary M" sort="Horowitz, Mary M" uniqKey="Horowitz M" first="Mary M." last="Horowitz">Mary M. Horowitz</name>
<name sortKey="Isola, Luis M" sort="Isola, Luis M" uniqKey="Isola L" first="Luis M." last="Isola">Luis M. Isola</name>
<name sortKey="Jacobsohn, David A" sort="Jacobsohn, David A" uniqKey="Jacobsohn D" first="David A." last="Jacobsohn">David A. Jacobsohn</name>
<name sortKey="Jagasia, Madan H" sort="Jagasia, Madan H" uniqKey="Jagasia M" first="Madan H." last="Jagasia">Madan H. Jagasia</name>
<name sortKey="Klein, John P" sort="Klein, John P" uniqKey="Klein J" first="John P." last="Klein">John P. Klein</name>
<name sortKey="Klumpp, Thomas R" sort="Klumpp, Thomas R" uniqKey="Klumpp T" first="Thomas R." last="Klumpp">Thomas R. Klumpp</name>
<name sortKey="Lee, Stephanie J" sort="Lee, Stephanie J" uniqKey="Lee S" first="Stephanie J." last="Lee">Stephanie J. Lee</name>
<name sortKey="Pavletic, Steven Z" sort="Pavletic, Steven Z" uniqKey="Pavletic S" first="Steven Z." last="Pavletic">Steven Z. Pavletic</name>
<name sortKey="Petersdorf, Effie W" sort="Petersdorf, Effie W" uniqKey="Petersdorf E" first="Effie W." last="Petersdorf">Effie W. Petersdorf</name>
<name sortKey="Spellman, Stephen R" sort="Spellman, Stephen R" uniqKey="Spellman S" first="Stephen R." last="Spellman">Stephen R. Spellman</name>
<name sortKey="Weisdorf, Daniel J" sort="Weisdorf, Daniel J" uniqKey="Weisdorf D" first="Daniel J." last="Weisdorf">Daniel J. Weisdorf</name>
<name sortKey="Wingard, John R" sort="Wingard, John R" uniqKey="Wingard J" first="John R." last="Wingard">John R. Wingard</name>
</country>
<country name="France">
<region name="Auvergne-Rhône-Alpes">
<name sortKey="Cahn, Jean Yves Y" sort="Cahn, Jean Yves Y" uniqKey="Cahn J" first="Jean-Yves Y." last="Cahn">Jean-Yves Y. Cahn</name>
</region>
</country>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Gale, Robert P" sort="Gale, Robert P" uniqKey="Gale R" first="Robert P." last="Gale">Robert P. Gale</name>
</region>
</country>
<country name="Italie">
<noRegion>
<name sortKey="Santarone, Stella" sort="Santarone, Stella" uniqKey="Santarone S" first="Stella" last="Santarone">Stella Santarone</name>
</noRegion>
</country>
<country name="Pays-Bas">
<noRegion>
<name sortKey="Schouten, Harry C" sort="Schouten, Harry C" uniqKey="Schouten H" first="Harry C." last="Schouten">Harry C. Schouten</name>
</noRegion>
<name sortKey="Verdonck, Leo F" sort="Verdonck, Leo F" uniqKey="Verdonck L" first="Leo F." last="Verdonck">Leo F. Verdonck</name>
</country>
</tree>
</affiliations>
</record>

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