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Targeted pretransplant host lymphocyte depletion prior to T‐cell depleted reduced‐intensity allogeneic stem cell transplantation
Summary Mixed chimaerism and graft rejection are higher after reduced‐intensity allogeneic stem cell transplantation (RIST) with T‐cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would ab...
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| Published in: | British journal of haematology 2004-09, Vol.126 (6), p.837-843 |
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| Main Authors: | , , , , , , , , , , , , , , , |
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| cites | cdi_FETCH-LOGICAL-c4413-d25048d81c6261668a652a21684ea8cd9c247eaee9d12b27cbaa6f72d1e7c4b43 |
| container_end_page | 843 |
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| container_title | British journal of haematology |
| container_volume | 126 |
| creator | Bishop, Michael R. Steinberg, Seth M. Gress, Ronald E. Hardy, Nancy M. Marchigiani, Donna Kasten‐Sportes, Claude Dean, Robert Pavletic, Steven Z. Gea‐Banacloche, Juan Castro, Kathleen Hakim, Fran Krumlauf, Michael Read, Elizabeth J. Carter, Charles Leitman, Susan F. Fowler, Daniel H. |
| description | Summary
Mixed chimaerism and graft rejection are higher after reduced‐intensity allogeneic stem cell transplantation (RIST) with T‐cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would abrogate graft rejection and promote donor chimaerism. Lymphocyte‐depleting chemotherapy was administered at conventional doses to subjects prior to RIST with the intent of decreasing CD4+ counts to |
| doi_str_mv | 10.1111/j.1365-2141.2004.05133.x |
| format | article |
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Mixed chimaerism and graft rejection are higher after reduced‐intensity allogeneic stem cell transplantation (RIST) with T‐cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would abrogate graft rejection and promote donor chimaerism. Lymphocyte‐depleting chemotherapy was administered at conventional doses to subjects prior to RIST with the intent of decreasing CD4+ counts to <0·05 × 109cells/l. Subjects (n = 18) then received reduced‐intensity conditioning followed by ex vivo TCD human leucocyte antigen‐matched sibling allografts. All evaluable patients (n = 17) were engrafted; there were no late graft failures. At day +28 post‐RIST, 12 patients showed complete donor chimaerism. Mixed chimaerism in the remaining five patients was associated with higher numbers of circulating host CD3+ cells (P = 0·0032) after lymphocyte‐depleting chemotherapy and was preferentially observed in T lymphoid rather than myeloid cells. Full donor chimaerism was achieved in all patients after planned donor lymphocyte infusions. These data reflect the importance of host immune status prior to RIST and suggest that targeted host lymphocyte depletion facilitates the engraftment of TCD allografts. Targeted lymphocyte depletion may permit an individualized approach to conditioning based on host immune status prior to RIST.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/j.1365-2141.2004.05133.x</identifier><identifier>PMID: 15352988</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; allogeneic ; Antigens, CD34 - analysis ; Biological and medical sciences ; Breast Neoplasms - therapy ; CD4 Lymphocyte Count ; Female ; graft rejection ; Graft Rejection - prevention & control ; Graft Survival ; Graft vs Host Disease - prevention & control ; Hematologic and hematopoietic diseases ; Hematology ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation - methods ; Humans ; Lymphocyte Depletion - methods ; Lymphocyte Transfusion ; Medical sciences ; Middle Aged ; reduced‐intensity ; T-Lymphocytes - immunology ; Transplantation Chimera ; Transplantation Conditioning - methods ; T‐cell depletion</subject><ispartof>British journal of haematology, 2004-09, Vol.126 (6), p.837-843</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. Sep 2, 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4413-d25048d81c6261668a652a21684ea8cd9c247eaee9d12b27cbaa6f72d1e7c4b43</citedby><cites>FETCH-LOGICAL-c4413-d25048d81c6261668a652a21684ea8cd9c247eaee9d12b27cbaa6f72d1e7c4b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16086794$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15352988$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bishop, Michael R.</creatorcontrib><creatorcontrib>Steinberg, Seth M.</creatorcontrib><creatorcontrib>Gress, Ronald E.</creatorcontrib><creatorcontrib>Hardy, Nancy M.</creatorcontrib><creatorcontrib>Marchigiani, Donna</creatorcontrib><creatorcontrib>Kasten‐Sportes, Claude</creatorcontrib><creatorcontrib>Dean, Robert</creatorcontrib><creatorcontrib>Pavletic, Steven Z.</creatorcontrib><creatorcontrib>Gea‐Banacloche, Juan</creatorcontrib><creatorcontrib>Castro, Kathleen</creatorcontrib><creatorcontrib>Hakim, Fran</creatorcontrib><creatorcontrib>Krumlauf, Michael</creatorcontrib><creatorcontrib>Read, Elizabeth J.</creatorcontrib><creatorcontrib>Carter, Charles</creatorcontrib><creatorcontrib>Leitman, Susan F.</creatorcontrib><creatorcontrib>Fowler, Daniel H.</creatorcontrib><title>Targeted pretransplant host lymphocyte depletion prior to T‐cell depleted reduced‐intensity allogeneic stem cell transplantation</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
Mixed chimaerism and graft rejection are higher after reduced‐intensity allogeneic stem cell transplantation (RIST) with T‐cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would abrogate graft rejection and promote donor chimaerism. Lymphocyte‐depleting chemotherapy was administered at conventional doses to subjects prior to RIST with the intent of decreasing CD4+ counts to <0·05 × 109cells/l. Subjects (n = 18) then received reduced‐intensity conditioning followed by ex vivo TCD human leucocyte antigen‐matched sibling allografts. All evaluable patients (n = 17) were engrafted; there were no late graft failures. At day +28 post‐RIST, 12 patients showed complete donor chimaerism. Mixed chimaerism in the remaining five patients was associated with higher numbers of circulating host CD3+ cells (P = 0·0032) after lymphocyte‐depleting chemotherapy and was preferentially observed in T lymphoid rather than myeloid cells. Full donor chimaerism was achieved in all patients after planned donor lymphocyte infusions. These data reflect the importance of host immune status prior to RIST and suggest that targeted host lymphocyte depletion facilitates the engraftment of TCD allografts. Targeted lymphocyte depletion may permit an individualized approach to conditioning based on host immune status prior to RIST.</description><subject>Adult</subject><subject>allogeneic</subject><subject>Antigens, CD34 - analysis</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - therapy</subject><subject>CD4 Lymphocyte Count</subject><subject>Female</subject><subject>graft rejection</subject><subject>Graft Rejection - prevention & control</subject><subject>Graft Survival</subject><subject>Graft vs Host Disease - prevention & control</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Hematopoiesis</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Humans</subject><subject>Lymphocyte Depletion - methods</subject><subject>Lymphocyte Transfusion</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>reduced‐intensity</subject><subject>T-Lymphocytes - immunology</subject><subject>Transplantation Chimera</subject><subject>Transplantation Conditioning - methods</subject><subject>T‐cell depletion</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqNkMFu1DAQhi1ERZfCKyALiWNSj-M4zoEDVECLKnFZzpbXnm2z8ibB9ormxoEH4Bl5EpxuxF7riy3P9_8z8xNCgZWQz-WuhErWBQcBJWdMlKyGqiofnpHV_8JzsmKMNQUwoc7Jyxh3jEGVwRfkHOqq5q1SK_J7bcIdJnR0DJiC6ePoTZ_o_RAT9dN-vB_slJA6HD2mbugz1w2BpoGu__76Y9H7pZYtArqDRZf_uz5hH7s0UeP9cIc9dpbGhHv6qDg1MrPnK3K2NT7i6-W-IN8_f1pfXRe3377cXH24LawQUBWO13kXp8BKLkFKZWTNDQepBBplXWu5aNAgtg74hjd2Y4zcNtwBNlZsRHVB3h59xzD8OGBMejccQp9bamiVbAVIyJA6QjYMMQbc6rzx3oRJA9Nz-nqn55D1HLKe09eP6euHLH2z-B82e3Qn4RJ3Bt4tgInW-G2OwXbxxEmmZNPOg74_cj87j9OTB9Afv17Pr-of5NalKA</recordid><startdate>200409</startdate><enddate>200409</enddate><creator>Bishop, Michael R.</creator><creator>Steinberg, Seth M.</creator><creator>Gress, Ronald E.</creator><creator>Hardy, Nancy M.</creator><creator>Marchigiani, Donna</creator><creator>Kasten‐Sportes, Claude</creator><creator>Dean, Robert</creator><creator>Pavletic, Steven Z.</creator><creator>Gea‐Banacloche, Juan</creator><creator>Castro, Kathleen</creator><creator>Hakim, Fran</creator><creator>Krumlauf, Michael</creator><creator>Read, Elizabeth J.</creator><creator>Carter, Charles</creator><creator>Leitman, Susan F.</creator><creator>Fowler, Daniel H.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Blackwell Publishing Ltd</general><scope>IQODW</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>7T5</scope><scope>H94</scope></search><sort><creationdate>200409</creationdate><title>Targeted pretransplant host lymphocyte depletion prior to T‐cell depleted reduced‐intensity allogeneic stem cell transplantation</title><author>Bishop, Michael R. ; Steinberg, Seth M. ; Gress, Ronald E. ; Hardy, Nancy M. ; Marchigiani, Donna ; Kasten‐Sportes, Claude ; Dean, Robert ; Pavletic, Steven Z. ; Gea‐Banacloche, Juan ; Castro, Kathleen ; Hakim, Fran ; Krumlauf, Michael ; Read, Elizabeth J. ; Carter, Charles ; Leitman, Susan F. ; Fowler, Daniel H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4413-d25048d81c6261668a652a21684ea8cd9c247eaee9d12b27cbaa6f72d1e7c4b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>allogeneic</topic><topic>Antigens, CD34 - analysis</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - therapy</topic><topic>CD4 Lymphocyte Count</topic><topic>Female</topic><topic>graft rejection</topic><topic>Graft Rejection - prevention & control</topic><topic>Graft Survival</topic><topic>Graft vs Host Disease - prevention & control</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Hematopoiesis</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Humans</topic><topic>Lymphocyte Depletion - methods</topic><topic>Lymphocyte Transfusion</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>reduced‐intensity</topic><topic>T-Lymphocytes - immunology</topic><topic>Transplantation Chimera</topic><topic>Transplantation Conditioning - methods</topic><topic>T‐cell depletion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bishop, Michael R.</creatorcontrib><creatorcontrib>Steinberg, Seth M.</creatorcontrib><creatorcontrib>Gress, Ronald E.</creatorcontrib><creatorcontrib>Hardy, Nancy M.</creatorcontrib><creatorcontrib>Marchigiani, Donna</creatorcontrib><creatorcontrib>Kasten‐Sportes, Claude</creatorcontrib><creatorcontrib>Dean, Robert</creatorcontrib><creatorcontrib>Pavletic, Steven Z.</creatorcontrib><creatorcontrib>Gea‐Banacloche, Juan</creatorcontrib><creatorcontrib>Castro, Kathleen</creatorcontrib><creatorcontrib>Hakim, Fran</creatorcontrib><creatorcontrib>Krumlauf, Michael</creatorcontrib><creatorcontrib>Read, Elizabeth J.</creatorcontrib><creatorcontrib>Carter, Charles</creatorcontrib><creatorcontrib>Leitman, Susan F.</creatorcontrib><creatorcontrib>Fowler, Daniel H.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bishop, Michael R.</au><au>Steinberg, Seth M.</au><au>Gress, Ronald E.</au><au>Hardy, Nancy M.</au><au>Marchigiani, Donna</au><au>Kasten‐Sportes, Claude</au><au>Dean, Robert</au><au>Pavletic, Steven Z.</au><au>Gea‐Banacloche, Juan</au><au>Castro, Kathleen</au><au>Hakim, Fran</au><au>Krumlauf, Michael</au><au>Read, Elizabeth J.</au><au>Carter, Charles</au><au>Leitman, Susan F.</au><au>Fowler, Daniel H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted pretransplant host lymphocyte depletion prior to T‐cell depleted reduced‐intensity allogeneic stem cell transplantation</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2004-09</date><risdate>2004</risdate><volume>126</volume><issue>6</issue><spage>837</spage><epage>843</epage><pages>837-843</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Summary
Mixed chimaerism and graft rejection are higher after reduced‐intensity allogeneic stem cell transplantation (RIST) with T‐cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would abrogate graft rejection and promote donor chimaerism. Lymphocyte‐depleting chemotherapy was administered at conventional doses to subjects prior to RIST with the intent of decreasing CD4+ counts to <0·05 × 109cells/l. Subjects (n = 18) then received reduced‐intensity conditioning followed by ex vivo TCD human leucocyte antigen‐matched sibling allografts. All evaluable patients (n = 17) were engrafted; there were no late graft failures. At day +28 post‐RIST, 12 patients showed complete donor chimaerism. Mixed chimaerism in the remaining five patients was associated with higher numbers of circulating host CD3+ cells (P = 0·0032) after lymphocyte‐depleting chemotherapy and was preferentially observed in T lymphoid rather than myeloid cells. Full donor chimaerism was achieved in all patients after planned donor lymphocyte infusions. These data reflect the importance of host immune status prior to RIST and suggest that targeted host lymphocyte depletion facilitates the engraftment of TCD allografts. Targeted lymphocyte depletion may permit an individualized approach to conditioning based on host immune status prior to RIST.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15352988</pmid><doi>10.1111/j.1365-2141.2004.05133.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of haematology, 2004-09, Vol.126 (6), p.837-843 |
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| language | eng |
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| subjects | Adult allogeneic Antigens, CD34 - analysis Biological and medical sciences Breast Neoplasms - therapy CD4 Lymphocyte Count Female graft rejection Graft Rejection - prevention & control Graft Survival Graft vs Host Disease - prevention & control Hematologic and hematopoietic diseases Hematology Hematopoiesis Hematopoietic Stem Cell Transplantation - methods Humans Lymphocyte Depletion - methods Lymphocyte Transfusion Medical sciences Middle Aged reduced‐intensity T-Lymphocytes - immunology Transplantation Chimera Transplantation Conditioning - methods T‐cell depletion |
| title | Targeted pretransplant host lymphocyte depletion prior to T‐cell depleted reduced‐intensity allogeneic stem cell transplantation |
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