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Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors
Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated ( n = 18) and mismatched related (haploidentical, n = 29) donor...
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| Published in: | Best practice & research. Clinical haematology 2011-09, Vol.24 (3), p.403-411 |
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| container_title | Best practice & research. Clinical haematology |
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| creator | Lang, Peter, MD, PhD Pfeiffer, Matthias, MD Teltschik, Heiko-Manuel, MD Schlegel, Patrick, MD Feuchtinger, Tobias, MD, PhD Ebinger, Martin, MD Klingebiel, Thomas, MD, PhD Bader, Peter, MD, PhD Schlegel, Paul-Gerhard, MD, PhD Beck, James, MD, PhD Greil, Johann, MD, PhD Handgretinger, Rupert, MD, PhD |
| description | Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated ( n = 18) and mismatched related (haploidentical, n = 29) donors. CD34 + selection with magnetic microbeads resulted in 8 × 103 /kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/μL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/μL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreasing and increasing activity. Patients with consistently high or increasing activity had significantly lower relapse probability than patients with consistently low or decreasing levels (0.18 vs 0.73 at 2 years, p |
| doi_str_mv | 10.1016/j.beha.2011.04.009 |
| format | article |
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CD34 + selection with magnetic microbeads resulted in 8 × 103 /kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/μL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/μL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreasing and increasing activity. Patients with consistently high or increasing activity had significantly lower relapse probability than patients with consistently low or decreasing levels (0.18 vs 0.73 at 2 years, p < 0.05). The subgroup of patients with ALL showed similar results (0.75 vs 0.14 at 2 years, p < 0.05). Speed of T cell recovery had no influence. These data suggest that both achieving and maintaining a high level of NK activity may contribute to prevent relapse. Since NK activity could be markedly increased by in vitro stimulation with Interleukin 2 (IL-2), in vivo administration should be considered.</description><identifier>ISSN: 1521-6926</identifier><identifier>EISSN: 1532-1924</identifier><identifier>DOI: 10.1016/j.beha.2011.04.009</identifier><identifier>PMID: 21925093</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adolescent ; Antigens, CD34 - immunology ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; haploidentical ; Hematologic Neoplasms - immunology ; Hematologic Neoplasms - therapy ; Hematology, Oncology and Palliative Medicine ; Humans ; K562 Cells ; Killer Cells, Natural - immunology ; leukemia ; Lymphocyte Depletion ; Male ; natural killer ; Peripheral Blood Stem Cell Transplantation ; Recurrence ; relapse ; Time Factors ; Tissue Donors ; transplantation ; Transplantation, Homologous</subject><ispartof>Best practice & research. Clinical haematology, 2011-09, Vol.24 (3), p.403-411</ispartof><rights>Elsevier Ltd</rights><rights>2011 Elsevier Ltd</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-2c64839889361f5bd780bb2bd2b6345fb1359339371aa3aa38a75a8c4b2001f63</citedby><cites>FETCH-LOGICAL-c410t-2c64839889361f5bd780bb2bd2b6345fb1359339371aa3aa38a75a8c4b2001f63</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/21925093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lang, Peter, MD, PhD</creatorcontrib><creatorcontrib>Pfeiffer, Matthias, MD</creatorcontrib><creatorcontrib>Teltschik, Heiko-Manuel, MD</creatorcontrib><creatorcontrib>Schlegel, Patrick, MD</creatorcontrib><creatorcontrib>Feuchtinger, Tobias, MD, PhD</creatorcontrib><creatorcontrib>Ebinger, Martin, MD</creatorcontrib><creatorcontrib>Klingebiel, Thomas, MD, PhD</creatorcontrib><creatorcontrib>Bader, Peter, MD, PhD</creatorcontrib><creatorcontrib>Schlegel, Paul-Gerhard, MD, PhD</creatorcontrib><creatorcontrib>Beck, James, MD, PhD</creatorcontrib><creatorcontrib>Greil, Johann, MD, PhD</creatorcontrib><creatorcontrib>Handgretinger, Rupert, MD, PhD</creatorcontrib><title>Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors</title><title>Best practice & research. Clinical haematology</title><addtitle>Best Pract Res Clin Haematol</addtitle><description>Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated ( n = 18) and mismatched related (haploidentical, n = 29) donors. CD34 + selection with magnetic microbeads resulted in 8 × 103 /kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/μL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/μL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreasing and increasing activity. Patients with consistently high or increasing activity had significantly lower relapse probability than patients with consistently low or decreasing levels (0.18 vs 0.73 at 2 years, p < 0.05). The subgroup of patients with ALL showed similar results (0.75 vs 0.14 at 2 years, p < 0.05). Speed of T cell recovery had no influence. These data suggest that both achieving and maintaining a high level of NK activity may contribute to prevent relapse. Since NK activity could be markedly increased by in vitro stimulation with Interleukin 2 (IL-2), in vivo administration should be considered.</description><subject>Adolescent</subject><subject>Antigens, CD34 - immunology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>haploidentical</subject><subject>Hematologic Neoplasms - immunology</subject><subject>Hematologic Neoplasms - therapy</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>K562 Cells</subject><subject>Killer Cells, Natural - immunology</subject><subject>leukemia</subject><subject>Lymphocyte Depletion</subject><subject>Male</subject><subject>natural killer</subject><subject>Peripheral Blood Stem Cell Transplantation</subject><subject>Recurrence</subject><subject>relapse</subject><subject>Time Factors</subject><subject>Tissue Donors</subject><subject>transplantation</subject><subject>Transplantation, Homologous</subject><issn>1521-6926</issn><issn>1532-1924</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp9kk2L1TAUhosozjj6B1xIdq5a89XeBkSQwS8YdOG4Dmlyys2dNKlJOnD_hT_ZhI4uXAiBhPC8h3Pe9zTNS4I7gsnw5tRNcFQdxYR0mHcYi0fNJekZbYmg_HF9U9IOgg4XzbOUThgzJih72lzQAvRYsMvm11eVt6gcurPOQUQanENKZ3tv8xlZP7sNvIaEwpZ1WACpORfsdgcNrA4yGJQyLPtXjsqn1SmfVbbBozmGBS0q62PBNh_BqSpQ3qCjWl2wBny2unRggg8xPW-ezMolePFwXzU_Pn64vf7c3nz79OX6_U2rOcG5pXrgIxPjKNhA5n4yhxFPE50MnQbG-3kirBdlXHYgSrFyRnXo1aj5RDEm88Cumtd73TWGnxukLBeb6gTKQ9iSHAUV_IAJLyTdSR1DShFmuUa7qHiWBMsahDzJGoSsQUjMZQmiiF49lN-mBcxfyR_nC_B2B6AMeW8hyqRttdrYCDpLE-z_67_7R66d9dXHOzhDOoUt-mKfJDJRieX3ugp1EwjBGPOes9_JHLDn</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Lang, Peter, MD, PhD</creator><creator>Pfeiffer, Matthias, MD</creator><creator>Teltschik, Heiko-Manuel, MD</creator><creator>Schlegel, Patrick, MD</creator><creator>Feuchtinger, Tobias, MD, PhD</creator><creator>Ebinger, Martin, MD</creator><creator>Klingebiel, Thomas, MD, PhD</creator><creator>Bader, Peter, MD, PhD</creator><creator>Schlegel, Paul-Gerhard, MD, PhD</creator><creator>Beck, James, MD, PhD</creator><creator>Greil, Johann, MD, PhD</creator><creator>Handgretinger, Rupert, MD, PhD</creator><general>Elsevier Ltd</general><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>20110901</creationdate><title>Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors</title><author>Lang, Peter, MD, PhD ; Pfeiffer, Matthias, MD ; Teltschik, Heiko-Manuel, MD ; Schlegel, Patrick, MD ; Feuchtinger, Tobias, MD, PhD ; Ebinger, Martin, MD ; Klingebiel, Thomas, MD, PhD ; Bader, Peter, MD, PhD ; Schlegel, Paul-Gerhard, MD, PhD ; Beck, James, MD, PhD ; Greil, Johann, MD, PhD ; Handgretinger, Rupert, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-2c64839889361f5bd780bb2bd2b6345fb1359339371aa3aa38a75a8c4b2001f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>Antigens, CD34 - immunology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>haploidentical</topic><topic>Hematologic Neoplasms - immunology</topic><topic>Hematologic Neoplasms - therapy</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>K562 Cells</topic><topic>Killer Cells, Natural - immunology</topic><topic>leukemia</topic><topic>Lymphocyte Depletion</topic><topic>Male</topic><topic>natural killer</topic><topic>Peripheral Blood Stem Cell Transplantation</topic><topic>Recurrence</topic><topic>relapse</topic><topic>Time Factors</topic><topic>Tissue Donors</topic><topic>transplantation</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lang, Peter, MD, PhD</creatorcontrib><creatorcontrib>Pfeiffer, Matthias, MD</creatorcontrib><creatorcontrib>Teltschik, Heiko-Manuel, MD</creatorcontrib><creatorcontrib>Schlegel, Patrick, MD</creatorcontrib><creatorcontrib>Feuchtinger, Tobias, MD, PhD</creatorcontrib><creatorcontrib>Ebinger, Martin, MD</creatorcontrib><creatorcontrib>Klingebiel, Thomas, MD, PhD</creatorcontrib><creatorcontrib>Bader, Peter, MD, PhD</creatorcontrib><creatorcontrib>Schlegel, Paul-Gerhard, MD, PhD</creatorcontrib><creatorcontrib>Beck, James, MD, PhD</creatorcontrib><creatorcontrib>Greil, Johann, MD, PhD</creatorcontrib><creatorcontrib>Handgretinger, Rupert, MD, PhD</creatorcontrib><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>Best practice & research. Clinical haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lang, Peter, MD, PhD</au><au>Pfeiffer, Matthias, MD</au><au>Teltschik, Heiko-Manuel, MD</au><au>Schlegel, Patrick, MD</au><au>Feuchtinger, Tobias, MD, PhD</au><au>Ebinger, Martin, MD</au><au>Klingebiel, Thomas, MD, PhD</au><au>Bader, Peter, MD, PhD</au><au>Schlegel, Paul-Gerhard, MD, PhD</au><au>Beck, James, MD, PhD</au><au>Greil, Johann, MD, PhD</au><au>Handgretinger, Rupert, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors</atitle><jtitle>Best practice & research. Clinical haematology</jtitle><addtitle>Best Pract Res Clin Haematol</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>24</volume><issue>3</issue><spage>403</spage><epage>411</epage><pages>403-411</pages><issn>1521-6926</issn><eissn>1532-1924</eissn><abstract>Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated ( n = 18) and mismatched related (haploidentical, n = 29) donors. CD34 + selection with magnetic microbeads resulted in 8 × 103 /kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/μL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/μL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreasing and increasing activity. Patients with consistently high or increasing activity had significantly lower relapse probability than patients with consistently low or decreasing levels (0.18 vs 0.73 at 2 years, p < 0.05). The subgroup of patients with ALL showed similar results (0.75 vs 0.14 at 2 years, p < 0.05). Speed of T cell recovery had no influence. These data suggest that both achieving and maintaining a high level of NK activity may contribute to prevent relapse. Since NK activity could be markedly increased by in vitro stimulation with Interleukin 2 (IL-2), in vivo administration should be considered.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>21925093</pmid><doi>10.1016/j.beha.2011.04.009</doi><tpages>9</tpages></addata></record> |
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| identifier | ISSN: 1521-6926 |
| ispartof | Best practice & research. Clinical haematology, 2011-09, Vol.24 (3), p.403-411 |
| issn | 1521-6926 1532-1924 |
| language | eng |
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| source | ScienceDirect Journals |
| subjects | Adolescent Antigens, CD34 - immunology Child Child, Preschool Female Follow-Up Studies haploidentical Hematologic Neoplasms - immunology Hematologic Neoplasms - therapy Hematology, Oncology and Palliative Medicine Humans K562 Cells Killer Cells, Natural - immunology leukemia Lymphocyte Depletion Male natural killer Peripheral Blood Stem Cell Transplantation Recurrence relapse Time Factors Tissue Donors transplantation Transplantation, Homologous |
| title | Natural killer cell activity influences outcome after T cell depleted stem cell transplantation from matched unrelated and haploidentical donors |
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