Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation
Abstract Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), b...
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| Veröffentlicht in: | Biology of blood and marrow transplantation 2015-09, Vol.21 (9), p.1589-1596 |
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| creator | Sobecks, Ronald M Wang, Tao Askar, Medhat Gallagher, Meighan M Haagenson, Michael Spellman, Stephen Fernandez-Vina, Marcelo Malmberg, Karl-Johan Müller, Carlheinz Battiwalla, Minoo Gajewski, James Verneris, Michael R Ringdén, Olle Marino, Susana Davies, Stella Dehn, Jason Bornhäuser, Martin Inamoto, Yoshihiro Woolfrey, Ann Shaw, Peter Pollack, Marilyn Weisdorf, Daniel Milller, Jeffrey Hurley, Carolyn Lee, Stephanie J Hsu, Katharine |
| description | Abstract Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2+ patients. AML patients with KIR2DS1+ , HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor–recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT. |
| doi_str_mv | 10.1016/j.bbmt.2015.05.002 |
| format | Article |
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Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2+ patients. AML patients with KIR2DS1+ , HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor–recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.</description><identifier>ISSN: 1083-8791</identifier><identifier>ISSN: 1523-6536</identifier><identifier>EISSN: 1523-6536</identifier><identifier>DOI: 10.1016/j.bbmt.2015.05.002</identifier><identifier>PMID: 25960307</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; AML/MDS ; Disease-Free Survival ; Female ; Genotype ; Graft vs Host Disease - genetics ; Graft vs Host Disease - mortality ; Graft vs Host Disease - prevention & control ; Hematology, Oncology and Palliative Medicine ; Hematopoietic Stem Cell Transplantation ; HLA-C Antigens - genetics ; Humans ; Killer immunoglobulin-like receptor (KIR) ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - mortality ; Leukemia, Myeloid, Acute - therapy ; Male ; Medicin och hälsovetenskap ; Middle Aged ; Myelodysplastic Syndromes - genetics ; Myelodysplastic Syndromes - mortality ; Myelodysplastic Syndromes - therapy ; Receptors, KIR2DL1 - genetics ; Reduced-intensity conditioning HCT ; Retrospective Studies ; Survival Rate ; Transplantation Conditioning</subject><ispartof>Biology of blood and marrow transplantation, 2015-09, Vol.21 (9), p.1589-1596</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-c734t-448e4c7f1b204e23ae58d92d954c778ae17fbc47b82e648809fce66c37102a923</citedby><cites>FETCH-LOGICAL-c734t-448e4c7f1b204e23ae58d92d954c778ae17fbc47b82e648809fce66c37102a923</cites><orcidid>0000-0002-5359-9606</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbmt.2015.05.002$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,553,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25960307$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:131872903$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Sobecks, Ronald M</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Askar, Medhat</creatorcontrib><creatorcontrib>Gallagher, Meighan M</creatorcontrib><creatorcontrib>Haagenson, Michael</creatorcontrib><creatorcontrib>Spellman, Stephen</creatorcontrib><creatorcontrib>Fernandez-Vina, Marcelo</creatorcontrib><creatorcontrib>Malmberg, Karl-Johan</creatorcontrib><creatorcontrib>Müller, Carlheinz</creatorcontrib><creatorcontrib>Battiwalla, Minoo</creatorcontrib><creatorcontrib>Gajewski, James</creatorcontrib><creatorcontrib>Verneris, Michael R</creatorcontrib><creatorcontrib>Ringdén, Olle</creatorcontrib><creatorcontrib>Marino, Susana</creatorcontrib><creatorcontrib>Davies, Stella</creatorcontrib><creatorcontrib>Dehn, Jason</creatorcontrib><creatorcontrib>Bornhäuser, Martin</creatorcontrib><creatorcontrib>Inamoto, Yoshihiro</creatorcontrib><creatorcontrib>Woolfrey, Ann</creatorcontrib><creatorcontrib>Shaw, Peter</creatorcontrib><creatorcontrib>Pollack, Marilyn</creatorcontrib><creatorcontrib>Weisdorf, Daniel</creatorcontrib><creatorcontrib>Milller, Jeffrey</creatorcontrib><creatorcontrib>Hurley, Carolyn</creatorcontrib><creatorcontrib>Lee, Stephanie J</creatorcontrib><creatorcontrib>Hsu, Katharine</creatorcontrib><title>Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation</title><title>Biology of blood and marrow transplantation</title><addtitle>Biol Blood Marrow Transplant</addtitle><description>Abstract Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2+ patients. AML patients with KIR2DS1+ , HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor–recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.</description><subject>Adult</subject><subject>AML/MDS</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Genotype</subject><subject>Graft vs Host Disease - genetics</subject><subject>Graft vs Host Disease - mortality</subject><subject>Graft vs Host Disease - prevention & control</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>HLA-C Antigens - genetics</subject><subject>Humans</subject><subject>Killer immunoglobulin-like receptor (KIR)</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - mortality</subject><subject>Leukemia, Myeloid, Acute - therapy</subject><subject>Male</subject><subject>Medicin och hälsovetenskap</subject><subject>Middle Aged</subject><subject>Myelodysplastic Syndromes - genetics</subject><subject>Myelodysplastic Syndromes - mortality</subject><subject>Myelodysplastic Syndromes - therapy</subject><subject>Receptors, KIR2DL1 - genetics</subject><subject>Reduced-intensity conditioning HCT</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><subject>Transplantation Conditioning</subject><issn>1083-8791</issn><issn>1523-6536</issn><issn>1523-6536</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9klFrFDEUhQdRbF39Az5IHn2Z9SaZmcyAFMqi3cVCodbnkM3cqdnOJGOSqey_N8NuqxUUArkk3zkJ954se0thSYFWH3bL7XaISwa0XEJawJ5lp7RkPK9KXj1PNdQ8r0VDT7JXIewAQBR18zI7YWVTAQdxmoXNMCodievIl801UbYl68tzcoHWxf2IgThLrqao3ZBq1UX05BrbSWObb2xEG0zck5WzrYnGWWNvyRoHFd3oDEajyQr7ntx4ZcPYKxvVTL3OXnSqD_jmuC-yb58_3azW-eXVxWZ1fplrwYuYF0WNhRYd3TIokHGFZd02rG3KdCpqhVR0W12Ibc2wKuoamk5jVWkuKDDVML7I8oNv-InjtJWjN4Pye-mUkceju1ShLCmvOE18809-9K79LXoQUk5rwRrgSXt20CZgwFajjV71Ty2e3FjzXd66e1mUXNRcJIP3RwPvfkwYohxM0Kl7yqKbgqQCCp5akuBFxg6o9i4Ej93jMxTknAy5k3My5JwMCWnB3Ix3f37wUfIQhQR8PACYRnJv0MugDdo0aeNRR9k683__s7_kujfWaNXf4R7Dzk3epmFLKgOTIL_O2ZyjSUsAzkrgvwCUTeI6</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Sobecks, Ronald M</creator><creator>Wang, Tao</creator><creator>Askar, Medhat</creator><creator>Gallagher, Meighan M</creator><creator>Haagenson, Michael</creator><creator>Spellman, Stephen</creator><creator>Fernandez-Vina, Marcelo</creator><creator>Malmberg, Karl-Johan</creator><creator>Müller, Carlheinz</creator><creator>Battiwalla, Minoo</creator><creator>Gajewski, James</creator><creator>Verneris, Michael R</creator><creator>Ringdén, Olle</creator><creator>Marino, Susana</creator><creator>Davies, Stella</creator><creator>Dehn, Jason</creator><creator>Bornhäuser, Martin</creator><creator>Inamoto, Yoshihiro</creator><creator>Woolfrey, Ann</creator><creator>Shaw, Peter</creator><creator>Pollack, Marilyn</creator><creator>Weisdorf, Daniel</creator><creator>Milller, Jeffrey</creator><creator>Hurley, Carolyn</creator><creator>Lee, Stephanie J</creator><creator>Hsu, Katharine</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><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-5359-9606</orcidid></search><sort><creationdate>20150901</creationdate><title>Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation</title><author>Sobecks, Ronald M ; Wang, Tao ; Askar, Medhat ; Gallagher, Meighan M ; Haagenson, Michael ; Spellman, Stephen ; Fernandez-Vina, Marcelo ; Malmberg, Karl-Johan ; Müller, Carlheinz ; Battiwalla, Minoo ; Gajewski, James ; Verneris, Michael R ; Ringdén, Olle ; Marino, Susana ; Davies, Stella ; Dehn, Jason ; Bornhäuser, Martin ; Inamoto, Yoshihiro ; Woolfrey, Ann ; Shaw, Peter ; Pollack, Marilyn ; Weisdorf, Daniel ; Milller, Jeffrey ; Hurley, Carolyn ; Lee, Stephanie J ; Hsu, Katharine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c734t-448e4c7f1b204e23ae58d92d954c778ae17fbc47b82e648809fce66c37102a923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>AML/MDS</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Genotype</topic><topic>Graft vs Host Disease - 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Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2+ patients. AML patients with KIR2DS1+ , HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor–recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25960307</pmid><doi>10.1016/j.bbmt.2015.05.002</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-5359-9606</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1083-8791 |
| ispartof | Biology of blood and marrow transplantation, 2015-09, Vol.21 (9), p.1589-1596 |
| issn | 1083-8791 1523-6536 1523-6536 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_513631 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Access via ScienceDirect (Elsevier); Alma/SFX Local Collection |
| subjects | Adult AML/MDS Disease-Free Survival Female Genotype Graft vs Host Disease - genetics Graft vs Host Disease - mortality Graft vs Host Disease - prevention & control Hematology, Oncology and Palliative Medicine Hematopoietic Stem Cell Transplantation HLA-C Antigens - genetics Humans Killer immunoglobulin-like receptor (KIR) Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - mortality Leukemia, Myeloid, Acute - therapy Male Medicin och hälsovetenskap Middle Aged Myelodysplastic Syndromes - genetics Myelodysplastic Syndromes - mortality Myelodysplastic Syndromes - therapy Receptors, KIR2DL1 - genetics Reduced-intensity conditioning HCT Retrospective Studies Survival Rate Transplantation Conditioning |
| title | Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T21%3A24%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Impact%20of%20KIR%20and%20HLA%20Genotypes%20on%20Outcomes%20after%20Reduced-Intensity%20Conditioning%20Hematopoietic%20Cell%20Transplantation&rft.jtitle=Biology%20of%20blood%20and%20marrow%20transplantation&rft.au=Sobecks,%20Ronald%20M&rft.date=2015-09-01&rft.volume=21&rft.issue=9&rft.spage=1589&rft.epage=1596&rft.pages=1589-1596&rft.issn=1083-8791&rft.eissn=1523-6536&rft_id=info:doi/10.1016/j.bbmt.2015.05.002&rft_dat=%3Cproquest_swepu%3E1704344878%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1704344878&rft_id=info:pmid/25960307&rft_els_id=S1083879115003250&rfr_iscdi=true |