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Heterogeneous Clearance of Antithymocyte Globulin after CD34 +-Selected Allogeneic Hematopoietic Progenitor Cell Transplantation
Antithymocyte globulins (ATG) are purified, concentrated preparations of polyclonal immunoglobulin G from hyperimmune serum of horses or rabbits immunized with human thymus lymphocytes. Both the horse and the rabbit products induce immunosuppression as a result of lymphocyte depletion and immune mod...
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Published in: | Biology of blood and marrow transplantation 2005-08, Vol.11 (8), p.609-618 |
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description | Antithymocyte globulins (ATG) are purified, concentrated preparations of polyclonal immunoglobulin G from hyperimmune serum of horses or rabbits immunized with human thymus lymphocytes. Both the horse and the rabbit products induce immunosuppression as a result of lymphocyte depletion and immune modulation. The exact mechanism of action is unknown but may include T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Both horse and rabbit ATG include multiple antibodies against T-cell surface antigens and have been used extensively in allogeneic hematopoietic progenitor cell transplantation (HPCT) for the treatment and prevention of graft-versus-host disease or graft rejection. To quantify the active ATG after HPCT, we developed a flow-based assay to measure residual ATG capable of binding to lymphocytes. In contrast to prior assays that measure total rabbit or horse immunoglobulin, this assay quantitates only the antibody capable of binding to lymphocytes, which presumably reflects the functionally active fraction of the xenoantiserum. Thirty patients with hematologic malignancies underwent T cell-depleted HPCT and had ATG levels assayed during the peritransplantation period. The time required for ATG levels to decay to background was quite variable (mean, 46 days; range, 14-91 days), although most patients demonstrated a rapid early clearance followed by a slower decline. The actual mean half-life was 6.8 days (range, 2.4-14.0 days). The persistence of ATG for months after administration has significant implications for the pace of immune reconstitution after transplantation and is a potentially confounding variable in any study that involves early administration of donor lymphocyte infusions or other cellular transfer. These findings indicate that ATG levels should be explicitly measured in studies that involve early donor lymphocyte administration so that proper conclusions regarding dose, safety, and efficacy can be reached. |
doi_str_mv | 10.1016/j.bbmt.2005.05.001 |
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Both the horse and the rabbit products induce immunosuppression as a result of lymphocyte depletion and immune modulation. The exact mechanism of action is unknown but may include T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Both horse and rabbit ATG include multiple antibodies against T-cell surface antigens and have been used extensively in allogeneic hematopoietic progenitor cell transplantation (HPCT) for the treatment and prevention of graft-versus-host disease or graft rejection. To quantify the active ATG after HPCT, we developed a flow-based assay to measure residual ATG capable of binding to lymphocytes. In contrast to prior assays that measure total rabbit or horse immunoglobulin, this assay quantitates only the antibody capable of binding to lymphocytes, which presumably reflects the functionally active fraction of the xenoantiserum. Thirty patients with hematologic malignancies underwent T cell-depleted HPCT and had ATG levels assayed during the peritransplantation period. The time required for ATG levels to decay to background was quite variable (mean, 46 days; range, 14-91 days), although most patients demonstrated a rapid early clearance followed by a slower decline. The actual mean half-life was 6.8 days (range, 2.4-14.0 days). The persistence of ATG for months after administration has significant implications for the pace of immune reconstitution after transplantation and is a potentially confounding variable in any study that involves early administration of donor lymphocyte infusions or other cellular transfer. These findings indicate that ATG levels should be explicitly measured in studies that involve early donor lymphocyte administration so that proper conclusions regarding dose, safety, and efficacy can be reached.</description><identifier>ISSN: 1083-8791</identifier><identifier>EISSN: 1523-6536</identifier><identifier>DOI: 10.1016/j.bbmt.2005.05.001</identifier><identifier>PMID: 16041311</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Antigens, CD34 ; Antilymphocyte globulin ; Antilymphocyte Serum - administration & dosage ; Antilymphocyte Serum - blood ; Antithymocyte globulin ; Donor lymphocyte infusion ; Female ; Hematologic Neoplasms - therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune reconstitution ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - blood ; Lymphocyte Depletion - methods ; Male ; Middle Aged ; T-cell depletion ; T-Lymphocytes - immunology ; Transplantation, Homologous</subject><ispartof>Biology of blood and marrow transplantation, 2005-08, Vol.11 (8), p.609-618</ispartof><rights>2005 American Society for Blood and Marrow Transplantation</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-74d0512da64e9aec76d33736502b0ba2ca9ba269df3826163aef74ee1a52f6643</citedby><cites>FETCH-LOGICAL-c464t-74d0512da64e9aec76d33736502b0ba2ca9ba269df3826163aef74ee1a52f6643</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/16041311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kakhniashvili, Irina</creatorcontrib><creatorcontrib>Filicko, Joanne</creatorcontrib><creatorcontrib>Kraft, Walter K.</creatorcontrib><creatorcontrib>Flomenberg, Neal</creatorcontrib><title>Heterogeneous Clearance of Antithymocyte Globulin after CD34 +-Selected Allogeneic Hematopoietic Progenitor Cell Transplantation</title><title>Biology of blood and marrow transplantation</title><addtitle>Biol Blood Marrow Transplant</addtitle><description>Antithymocyte globulins (ATG) are purified, concentrated preparations of polyclonal immunoglobulin G from hyperimmune serum of horses or rabbits immunized with human thymus lymphocytes. Both the horse and the rabbit products induce immunosuppression as a result of lymphocyte depletion and immune modulation. The exact mechanism of action is unknown but may include T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Both horse and rabbit ATG include multiple antibodies against T-cell surface antigens and have been used extensively in allogeneic hematopoietic progenitor cell transplantation (HPCT) for the treatment and prevention of graft-versus-host disease or graft rejection. To quantify the active ATG after HPCT, we developed a flow-based assay to measure residual ATG capable of binding to lymphocytes. In contrast to prior assays that measure total rabbit or horse immunoglobulin, this assay quantitates only the antibody capable of binding to lymphocytes, which presumably reflects the functionally active fraction of the xenoantiserum. Thirty patients with hematologic malignancies underwent T cell-depleted HPCT and had ATG levels assayed during the peritransplantation period. The time required for ATG levels to decay to background was quite variable (mean, 46 days; range, 14-91 days), although most patients demonstrated a rapid early clearance followed by a slower decline. The actual mean half-life was 6.8 days (range, 2.4-14.0 days). The persistence of ATG for months after administration has significant implications for the pace of immune reconstitution after transplantation and is a potentially confounding variable in any study that involves early administration of donor lymphocyte infusions or other cellular transfer. These findings indicate that ATG levels should be explicitly measured in studies that involve early donor lymphocyte administration so that proper conclusions regarding dose, safety, and efficacy can be reached.</description><subject>Adult</subject><subject>Aged</subject><subject>Antigens, CD34</subject><subject>Antilymphocyte globulin</subject><subject>Antilymphocyte Serum - administration & dosage</subject><subject>Antilymphocyte Serum - blood</subject><subject>Antithymocyte globulin</subject><subject>Donor lymphocyte infusion</subject><subject>Female</subject><subject>Hematologic Neoplasms - therapy</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Immune reconstitution</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - blood</subject><subject>Lymphocyte Depletion - methods</subject><subject>Male</subject><subject>Middle Aged</subject><subject>T-cell depletion</subject><subject>T-Lymphocytes - immunology</subject><subject>Transplantation, Homologous</subject><issn>1083-8791</issn><issn>1523-6536</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNp9kE9LIzEYh4O42Kr7BTxITl5kuskkk5kBL6VqKwi7oHsOmcw7mpKZ1CQVetuPvpm24E0I-QO_30PeB6ErSmaUUPFrPWuaPs5yQorZuAg9QVNa5CwTBROn6U4qllVlTSfoPIQ1IaTkVX2GJlQQThmlU_RvBRG8e4MB3DbghQXl1aABuw7Ph2ji-653ehcBL61rttYMWHWpgRf3jOPb7AUs6Agtnlu7pxiNV9Cr6DbOQEyvP3u6iS51wFr8mvhhY9UQVTRuuEQ_OmUD_DyeF-jv48PrYpU9_14-LebPmeaCx6zkLSlo3irBoVagS9EyVjJRkLwhjcq1qtMu6rZjVS6oYAq6kgNQVeSdEJxdoJsDd-PdxxZClL0JOn1I7SeXoiKiTMQUzA9B7V0IHjq58aZXficpkaN3uZajdzl6l-MiNJWuj_Rt00P7VTmKToG7QwDSjJ8GvAzaQBLdGp8EytaZ7_j_AdSflcg</recordid><startdate>20050801</startdate><enddate>20050801</enddate><creator>Kakhniashvili, Irina</creator><creator>Filicko, Joanne</creator><creator>Kraft, Walter K.</creator><creator>Flomenberg, Neal</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>20050801</creationdate><title>Heterogeneous Clearance of Antithymocyte Globulin after CD34 +-Selected Allogeneic Hematopoietic Progenitor Cell Transplantation</title><author>Kakhniashvili, Irina ; Filicko, Joanne ; Kraft, Walter K. ; Flomenberg, Neal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-74d0512da64e9aec76d33736502b0ba2ca9ba269df3826163aef74ee1a52f6643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigens, CD34</topic><topic>Antilymphocyte globulin</topic><topic>Antilymphocyte Serum - administration & dosage</topic><topic>Antilymphocyte Serum - blood</topic><topic>Antithymocyte globulin</topic><topic>Donor lymphocyte infusion</topic><topic>Female</topic><topic>Hematologic Neoplasms - therapy</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Immune reconstitution</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - blood</topic><topic>Lymphocyte Depletion - methods</topic><topic>Male</topic><topic>Middle Aged</topic><topic>T-cell depletion</topic><topic>T-Lymphocytes - immunology</topic><topic>Transplantation, Homologous</topic><toplevel>online_resources</toplevel><creatorcontrib>Kakhniashvili, Irina</creatorcontrib><creatorcontrib>Filicko, Joanne</creatorcontrib><creatorcontrib>Kraft, Walter K.</creatorcontrib><creatorcontrib>Flomenberg, Neal</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>Kakhniashvili, Irina</au><au>Filicko, Joanne</au><au>Kraft, Walter K.</au><au>Flomenberg, Neal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heterogeneous Clearance of Antithymocyte Globulin after CD34 +-Selected Allogeneic Hematopoietic Progenitor Cell Transplantation</atitle><jtitle>Biology of blood and marrow transplantation</jtitle><addtitle>Biol Blood Marrow Transplant</addtitle><date>2005-08-01</date><risdate>2005</risdate><volume>11</volume><issue>8</issue><spage>609</spage><epage>618</epage><pages>609-618</pages><issn>1083-8791</issn><eissn>1523-6536</eissn><abstract>Antithymocyte globulins (ATG) are purified, concentrated preparations of polyclonal immunoglobulin G from hyperimmune serum of horses or rabbits immunized with human thymus lymphocytes. Both the horse and the rabbit products induce immunosuppression as a result of lymphocyte depletion and immune modulation. The exact mechanism of action is unknown but may include T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Both horse and rabbit ATG include multiple antibodies against T-cell surface antigens and have been used extensively in allogeneic hematopoietic progenitor cell transplantation (HPCT) for the treatment and prevention of graft-versus-host disease or graft rejection. To quantify the active ATG after HPCT, we developed a flow-based assay to measure residual ATG capable of binding to lymphocytes. In contrast to prior assays that measure total rabbit or horse immunoglobulin, this assay quantitates only the antibody capable of binding to lymphocytes, which presumably reflects the functionally active fraction of the xenoantiserum. Thirty patients with hematologic malignancies underwent T cell-depleted HPCT and had ATG levels assayed during the peritransplantation period. The time required for ATG levels to decay to background was quite variable (mean, 46 days; range, 14-91 days), although most patients demonstrated a rapid early clearance followed by a slower decline. The actual mean half-life was 6.8 days (range, 2.4-14.0 days). The persistence of ATG for months after administration has significant implications for the pace of immune reconstitution after transplantation and is a potentially confounding variable in any study that involves early administration of donor lymphocyte infusions or other cellular transfer. 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subjects | Adult Aged Antigens, CD34 Antilymphocyte globulin Antilymphocyte Serum - administration & dosage Antilymphocyte Serum - blood Antithymocyte globulin Donor lymphocyte infusion Female Hematologic Neoplasms - therapy Hematopoietic Stem Cell Transplantation Humans Immune reconstitution Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - blood Lymphocyte Depletion - methods Male Middle Aged T-cell depletion T-Lymphocytes - immunology Transplantation, Homologous |
title | Heterogeneous Clearance of Antithymocyte Globulin after CD34 +-Selected Allogeneic Hematopoietic Progenitor Cell Transplantation |
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