Persistence of clonal T-cell expansions following high-dose chemotherapy and autologous peripheral blood progenitor cell rescue
Analysing the regeneration of T lymphocytes after high-dose chemotherapy with autologous peripheral blood progenitor cell rescue (PBPCR) may help elucidate the mechanisms of immune recovery. The T-cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high-dose chemotherap...
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| Veröffentlicht in: | British journal of haematology 2000-12, Vol.111 (3), p.766-773 |
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| creator | PROTHEROE, Andrew S PICKARD, Christopher JOHNSON, Peter W. M CRADDOCK, Tina SHEFTA, Jahan SHORT, Kath LANCASTER, Fiona SELBY, Peter J HENWOOD, Judy BOYLSTON, Arthur W |
| description | Analysing the regeneration of T lymphocytes after high-dose chemotherapy with autologous peripheral blood progenitor cell rescue (PBPCR) may help elucidate the mechanisms of immune recovery. The T-cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high-dose chemotherapy was analysed by flow cytometry, before and after treatment. Four patients were found to have a stable expansion present (TCRBV3, 17, 21 and 22) ranging from 8% to 42% of the CD4(+) or CD8(+) repertoire. We demonstrated that, in these patients, following high-dose chemotherapy and autologous stem cell transplantation, the clonal expansions reappeared in peripheral blood and returned to pretransplant levels. Three expansions (CD3(+)CD8(+)TCRBV3(+), CD3(+)CD4(+)TCRBV21(+) and CD3(+)CD8(+)TCRBV22(+)) were further defined by sequence analysis of the complementarity-determining region (CDR)3 portion within the TCR rearrangements. These were shown to be predominantly clonal, with the same sequences being identified in peripheral blood before and after PBPCR, providing evidence that the overwhelming majority of T cells in these expansions arise from mature lymphocytes. This study demonstrated that patients undergoing autologous PBPCR for high-dose chemotherapy regenerate clonal expansions, consistent with pretreatment levels. They also regenerate T-cell repertoires with each TCRBV family represented to a similar level as that prior to high-dose chemotherapy. |
| doi_str_mv | 10.1046/j.1365-2141.2000.02427.x |
| format | Article |
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M ; CRADDOCK, Tina ; SHEFTA, Jahan ; SHORT, Kath ; LANCASTER, Fiona ; SELBY, Peter J ; HENWOOD, Judy ; BOYLSTON, Arthur W</creator><creatorcontrib>PROTHEROE, Andrew S ; PICKARD, Christopher ; JOHNSON, Peter W. M ; CRADDOCK, Tina ; SHEFTA, Jahan ; SHORT, Kath ; LANCASTER, Fiona ; SELBY, Peter J ; HENWOOD, Judy ; BOYLSTON, Arthur W</creatorcontrib><description>Analysing the regeneration of T lymphocytes after high-dose chemotherapy with autologous peripheral blood progenitor cell rescue (PBPCR) may help elucidate the mechanisms of immune recovery. The T-cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high-dose chemotherapy was analysed by flow cytometry, before and after treatment. Four patients were found to have a stable expansion present (TCRBV3, 17, 21 and 22) ranging from 8% to 42% of the CD4(+) or CD8(+) repertoire. We demonstrated that, in these patients, following high-dose chemotherapy and autologous stem cell transplantation, the clonal expansions reappeared in peripheral blood and returned to pretransplant levels. Three expansions (CD3(+)CD8(+)TCRBV3(+), CD3(+)CD4(+)TCRBV21(+) and CD3(+)CD8(+)TCRBV22(+)) were further defined by sequence analysis of the complementarity-determining region (CDR)3 portion within the TCR rearrangements. These were shown to be predominantly clonal, with the same sequences being identified in peripheral blood before and after PBPCR, providing evidence that the overwhelming majority of T cells in these expansions arise from mature lymphocytes. This study demonstrated that patients undergoing autologous PBPCR for high-dose chemotherapy regenerate clonal expansions, consistent with pretreatment levels. They also regenerate T-cell repertoires with each TCRBV family represented to a similar level as that prior to high-dose chemotherapy.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1046/j.1365-2141.2000.02427.x</identifier><identifier>PMID: 11122136</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford: Blackwell</publisher><subject>Amino Acid Sequence ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Antineoplastic Agents, Alkylating - therapeutic use ; Biological and medical sciences ; Bone Marrow Purging ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Breast Neoplasms - immunology ; Breast Neoplasms - surgery ; Carcinoma, Small Cell - immunology ; Carcinoma, Small Cell - surgery ; Carmustine - therapeutic use ; Cyclophosphamide - therapeutic use ; Drug Administration Schedule ; Female ; Flow Cytometry ; Fluorescent Antibody Technique, Direct ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Germinoma - immunology ; Germinoma - surgery ; Hematology ; Hematopoietic Stem Cell Transplantation ; Humans ; Lung Neoplasms - immunology ; Lung Neoplasms - surgery ; Lymphoma, Non-Hodgkin - immunology ; Lymphoma, Non-Hodgkin - surgery ; Male ; Medical sciences ; Melanoma - immunology ; Melanoma - surgery ; Middle Aged ; Molecular Sequence Data ; Multiple Myeloma - immunology ; Multiple Myeloma - surgery ; Polymerase Chain Reaction - methods ; Receptor-CD3 Complex, Antigen, T-Cell - genetics ; T-Lymphocytes - immunology ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Transplantation, Autologous</subject><ispartof>British journal of haematology, 2000-12, Vol.111 (3), p.766-773</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. 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M</creatorcontrib><creatorcontrib>CRADDOCK, Tina</creatorcontrib><creatorcontrib>SHEFTA, Jahan</creatorcontrib><creatorcontrib>SHORT, Kath</creatorcontrib><creatorcontrib>LANCASTER, Fiona</creatorcontrib><creatorcontrib>SELBY, Peter J</creatorcontrib><creatorcontrib>HENWOOD, Judy</creatorcontrib><creatorcontrib>BOYLSTON, Arthur W</creatorcontrib><title>Persistence of clonal T-cell expansions following high-dose chemotherapy and autologous peripheral blood progenitor cell rescue</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Analysing the regeneration of T lymphocytes after high-dose chemotherapy with autologous peripheral blood progenitor cell rescue (PBPCR) may help elucidate the mechanisms of immune recovery. The T-cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high-dose chemotherapy was analysed by flow cytometry, before and after treatment. Four patients were found to have a stable expansion present (TCRBV3, 17, 21 and 22) ranging from 8% to 42% of the CD4(+) or CD8(+) repertoire. We demonstrated that, in these patients, following high-dose chemotherapy and autologous stem cell transplantation, the clonal expansions reappeared in peripheral blood and returned to pretransplant levels. Three expansions (CD3(+)CD8(+)TCRBV3(+), CD3(+)CD4(+)TCRBV21(+) and CD3(+)CD8(+)TCRBV22(+)) were further defined by sequence analysis of the complementarity-determining region (CDR)3 portion within the TCR rearrangements. These were shown to be predominantly clonal, with the same sequences being identified in peripheral blood before and after PBPCR, providing evidence that the overwhelming majority of T cells in these expansions arise from mature lymphocytes. This study demonstrated that patients undergoing autologous PBPCR for high-dose chemotherapy regenerate clonal expansions, consistent with pretreatment levels. They also regenerate T-cell repertoires with each TCRBV family represented to a similar level as that prior to high-dose chemotherapy.</description><subject>Amino Acid Sequence</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Antineoplastic Agents, Alkylating - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Purging</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - surgery</subject><subject>Carcinoma, Small Cell - immunology</subject><subject>Carcinoma, Small Cell - surgery</subject><subject>Carmustine - therapeutic use</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Drug Administration Schedule</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique, Direct</subject><subject>Gene Rearrangement, beta-Chain T-Cell Antigen Receptor</subject><subject>Germinoma - immunology</subject><subject>Germinoma - surgery</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Lung Neoplasms - immunology</subject><subject>Lung Neoplasms - surgery</subject><subject>Lymphoma, Non-Hodgkin - immunology</subject><subject>Lymphoma, Non-Hodgkin - surgery</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melanoma - immunology</subject><subject>Melanoma - surgery</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Multiple Myeloma - immunology</subject><subject>Multiple Myeloma - surgery</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Receptor-CD3 Complex, Antigen, T-Cell - genetics</subject><subject>T-Lymphocytes - immunology</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Transplantation, Autologous</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtOwzAURC0EgvL4BWTBOsF2HCdZooqXhAQLWFu2c92mcuNgJ6Jd8esktCorL-bM6PoghClJKeHibpXSTOQJo5ymjBCSEsZZkW6O0OwQHKPZmBTJWCjP0HmMK0JoRnJ6is4opYyN5Az9vEOITeyhNYC9xcb5Vjn8kRhwDsOmU21sfBux9c7576Zd4GWzWCa1j4DNEta-X0JQ3RartsZq6L3zCz9E3EFouilyWDvva9wFv4C26X3Af9sBohngEp1Y5SJc7d8L9Pn48DF_Tl7fnl7m96-JyYTok6KqraK1VlqDsbTKuQJQuWZQ6xwKY4ytNOeWaF1AVRCqDJRQ8EqUWoDIswt0s9sdz_gaIPZy5YcwfjVKWpVcVKzkI1TuIBN8jAGs7EKzVmErKZGTeLmSk185-ZWTePknXm7G6vV-f9BrqP-Le9MjcLsHVDTK2aBa08QDVxHKcpH9AsOikGU</recordid><startdate>20001201</startdate><enddate>20001201</enddate><creator>PROTHEROE, Andrew S</creator><creator>PICKARD, Christopher</creator><creator>JOHNSON, Peter W. 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Graft versus host reaction</topic><topic>Breast Neoplasms - immunology</topic><topic>Breast Neoplasms - surgery</topic><topic>Carcinoma, Small Cell - immunology</topic><topic>Carcinoma, Small Cell - surgery</topic><topic>Carmustine - therapeutic use</topic><topic>Cyclophosphamide - therapeutic use</topic><topic>Drug Administration Schedule</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fluorescent Antibody Technique, Direct</topic><topic>Gene Rearrangement, beta-Chain T-Cell Antigen Receptor</topic><topic>Germinoma - immunology</topic><topic>Germinoma - surgery</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Lung Neoplasms - immunology</topic><topic>Lung Neoplasms - surgery</topic><topic>Lymphoma, Non-Hodgkin - immunology</topic><topic>Lymphoma, Non-Hodgkin - surgery</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melanoma - immunology</topic><topic>Melanoma - surgery</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Multiple Myeloma - immunology</topic><topic>Multiple Myeloma - surgery</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Receptor-CD3 Complex, Antigen, T-Cell - genetics</topic><topic>T-Lymphocytes - immunology</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Transplantation, Autologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PROTHEROE, Andrew S</creatorcontrib><creatorcontrib>PICKARD, Christopher</creatorcontrib><creatorcontrib>JOHNSON, Peter W. 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M</au><au>CRADDOCK, Tina</au><au>SHEFTA, Jahan</au><au>SHORT, Kath</au><au>LANCASTER, Fiona</au><au>SELBY, Peter J</au><au>HENWOOD, Judy</au><au>BOYLSTON, Arthur W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Persistence of clonal T-cell expansions following high-dose chemotherapy and autologous peripheral blood progenitor cell rescue</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2000-12-01</date><risdate>2000</risdate><volume>111</volume><issue>3</issue><spage>766</spage><epage>773</epage><pages>766-773</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Analysing the regeneration of T lymphocytes after high-dose chemotherapy with autologous peripheral blood progenitor cell rescue (PBPCR) may help elucidate the mechanisms of immune recovery. The T-cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high-dose chemotherapy was analysed by flow cytometry, before and after treatment. Four patients were found to have a stable expansion present (TCRBV3, 17, 21 and 22) ranging from 8% to 42% of the CD4(+) or CD8(+) repertoire. We demonstrated that, in these patients, following high-dose chemotherapy and autologous stem cell transplantation, the clonal expansions reappeared in peripheral blood and returned to pretransplant levels. Three expansions (CD3(+)CD8(+)TCRBV3(+), CD3(+)CD4(+)TCRBV21(+) and CD3(+)CD8(+)TCRBV22(+)) were further defined by sequence analysis of the complementarity-determining region (CDR)3 portion within the TCR rearrangements. These were shown to be predominantly clonal, with the same sequences being identified in peripheral blood before and after PBPCR, providing evidence that the overwhelming majority of T cells in these expansions arise from mature lymphocytes. This study demonstrated that patients undergoing autologous PBPCR for high-dose chemotherapy regenerate clonal expansions, consistent with pretreatment levels. They also regenerate T-cell repertoires with each TCRBV family represented to a similar level as that prior to high-dose chemotherapy.</abstract><cop>Oxford</cop><pub>Blackwell</pub><pmid>11122136</pmid><doi>10.1046/j.1365-2141.2000.02427.x</doi><tpages>8</tpages></addata></record> |
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| ispartof | British journal of haematology, 2000-12, Vol.111 (3), p.766-773 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Amino Acid Sequence Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Antineoplastic Agents, Alkylating - therapeutic use Biological and medical sciences Bone Marrow Purging Bone marrow, stem cells transplantation. Graft versus host reaction Breast Neoplasms - immunology Breast Neoplasms - surgery Carcinoma, Small Cell - immunology Carcinoma, Small Cell - surgery Carmustine - therapeutic use Cyclophosphamide - therapeutic use Drug Administration Schedule Female Flow Cytometry Fluorescent Antibody Technique, Direct Gene Rearrangement, beta-Chain T-Cell Antigen Receptor Germinoma - immunology Germinoma - surgery Hematology Hematopoietic Stem Cell Transplantation Humans Lung Neoplasms - immunology Lung Neoplasms - surgery Lymphoma, Non-Hodgkin - immunology Lymphoma, Non-Hodgkin - surgery Male Medical sciences Melanoma - immunology Melanoma - surgery Middle Aged Molecular Sequence Data Multiple Myeloma - immunology Multiple Myeloma - surgery Polymerase Chain Reaction - methods Receptor-CD3 Complex, Antigen, T-Cell - genetics T-Lymphocytes - immunology Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation, Autologous |
| title | Persistence of clonal T-cell expansions following high-dose chemotherapy and autologous peripheral blood progenitor cell rescue |
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