Rapid immune reconstitution after a reduced‐intensity conditioning regimen and a CD3‐depleted haploidentical stem cell graft for paediatric refractory haematological malignancies
Summary The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft‐versus‐host disease (GvHD). We designed a reduced‐intensity conditioning regimen that...
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| Veröffentlicht in: | British journal of haematology 2006-11, Vol.135 (4), p.524-532 |
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| creator | Chen, Xiaohua Hale, Gregory A. Barfield, Raymond Benaim, Ely Leung, Wing H. Knowles, James Horwitz, Edwin M. Woodard, Paul Kasow, Kimberly Yusuf, Usman Behm, Frederick G. Hayden, Randall T. Shurtleff, Sheila A. Turner, Victoria Srivastava, Deo Kumar Handgretinger, Rupert |
| description | Summary
The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft‐versus‐host disease (GvHD). We designed a reduced‐intensity conditioning regimen that excluded total body irradiation and anti‐thymocyte globulin in order to expedite immune reconstitution after a CD3‐depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3+ T‐cells, T‐cell receptor (TCR) excision circle counts, TCRβ repertoire diversity and natural killer (NK)‐cells during the first 4 months post‐transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well‐tolerated regimen appears to accelerate immune recovery and shorten the duration of early post‐transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T‐cell reconstitution, retention of NK‐cells in the graft and induction of low grade GvHD may also enhance the potential anti‐cancer immune effect. |
| doi_str_mv | 10.1111/j.1365-2141.2006.06330.x |
| format | Article |
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The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft‐versus‐host disease (GvHD). We designed a reduced‐intensity conditioning regimen that excluded total body irradiation and anti‐thymocyte globulin in order to expedite immune reconstitution after a CD3‐depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3+ T‐cells, T‐cell receptor (TCR) excision circle counts, TCRβ repertoire diversity and natural killer (NK)‐cells during the first 4 months post‐transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well‐tolerated regimen appears to accelerate immune recovery and shorten the duration of early post‐transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T‐cell reconstitution, retention of NK‐cells in the graft and induction of low grade GvHD may also enhance the potential anti‐cancer immune effect.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/j.1365-2141.2006.06330.x</identifier><identifier>PMID: 17010105</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescent ; B-Lymphocytes - immunology ; Biological and medical sciences ; CD3 Complex - blood ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Graft Survival - immunology ; Graft vs Host Disease - immunology ; haploidentical haematopoietic stem cell transplantation ; Hematologic and hematopoietic diseases ; Hematologic Neoplasms - immunology ; Hematologic Neoplasms - therapy ; Hematopoietic Stem Cell Transplantation - methods ; Humans ; immune reconstitution ; Killer Cells, Natural - immunology ; Lymphocyte Count ; Lymphocyte Depletion ; Male ; Medical sciences ; Opportunistic Infections - immunology ; Opportunistic Infections - prevention & control ; Receptors, Antigen, T-Cell, alpha-beta - analysis ; reduced intensity conditioning regimen ; T-Lymphocyte Subsets - immunology ; Transplantation Chimera - immunology ; Transplantation Conditioning - methods ; T‐cell receptor beta CDR3 size spectratyping ; T‐cell receptor excision circle ; Viral Load ; Viremia - immunology ; Viremia - prevention & control</subject><ispartof>British journal of haematology, 2006-11, Vol.135 (4), p.524-532</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3970-bcda280d2695b36563250eaf87812b777f7b85246d3887bb39dc080f244185713</citedby><cites>FETCH-LOGICAL-c3970-bcda280d2695b36563250eaf87812b777f7b85246d3887bb39dc080f244185713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2141.2006.06330.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2141.2006.06330.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18245349$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17010105$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xiaohua</creatorcontrib><creatorcontrib>Hale, Gregory A.</creatorcontrib><creatorcontrib>Barfield, Raymond</creatorcontrib><creatorcontrib>Benaim, Ely</creatorcontrib><creatorcontrib>Leung, Wing H.</creatorcontrib><creatorcontrib>Knowles, James</creatorcontrib><creatorcontrib>Horwitz, Edwin M.</creatorcontrib><creatorcontrib>Woodard, Paul</creatorcontrib><creatorcontrib>Kasow, Kimberly</creatorcontrib><creatorcontrib>Yusuf, Usman</creatorcontrib><creatorcontrib>Behm, Frederick G.</creatorcontrib><creatorcontrib>Hayden, Randall T.</creatorcontrib><creatorcontrib>Shurtleff, Sheila A.</creatorcontrib><creatorcontrib>Turner, Victoria</creatorcontrib><creatorcontrib>Srivastava, Deo Kumar</creatorcontrib><creatorcontrib>Handgretinger, Rupert</creatorcontrib><title>Rapid immune reconstitution after a reduced‐intensity conditioning regimen and a CD3‐depleted haploidentical stem cell graft for paediatric refractory haematological malignancies</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft‐versus‐host disease (GvHD). We designed a reduced‐intensity conditioning regimen that excluded total body irradiation and anti‐thymocyte globulin in order to expedite immune reconstitution after a CD3‐depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3+ T‐cells, T‐cell receptor (TCR) excision circle counts, TCRβ repertoire diversity and natural killer (NK)‐cells during the first 4 months post‐transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well‐tolerated regimen appears to accelerate immune recovery and shorten the duration of early post‐transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T‐cell reconstitution, retention of NK‐cells in the graft and induction of low grade GvHD may also enhance the potential anti‐cancer immune effect.</description><subject>Adolescent</subject><subject>B-Lymphocytes - immunology</subject><subject>Biological and medical sciences</subject><subject>CD3 Complex - blood</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Graft Survival - immunology</subject><subject>Graft vs Host Disease - immunology</subject><subject>haploidentical haematopoietic stem cell transplantation</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematologic Neoplasms - immunology</subject><subject>Hematologic Neoplasms - therapy</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Humans</subject><subject>immune reconstitution</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lymphocyte Count</subject><subject>Lymphocyte Depletion</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Opportunistic Infections - immunology</subject><subject>Opportunistic Infections - prevention & control</subject><subject>Receptors, Antigen, T-Cell, alpha-beta - analysis</subject><subject>reduced intensity conditioning regimen</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>Transplantation Chimera - immunology</subject><subject>Transplantation Conditioning - methods</subject><subject>T‐cell receptor beta CDR3 size spectratyping</subject><subject>T‐cell receptor excision circle</subject><subject>Viral Load</subject><subject>Viremia - immunology</subject><subject>Viremia - prevention & control</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc-O1SAUxhujca6jr2DY6K4VSlvowoVe_4xmEhOja0LhtHLT0go0zt35CD6ND-STeDr3xtkKCwj8vnPg-7KMMFowHC8OBeNNnZesYkVJaVPQhnNa3NzLdv8u7mc7SqnIGa3kRfYoxgOljNOaPcwumKAMZ73Lfn_Wi7PETdPqgQQws4_JpTW52RPdJwhE47FdDdg_P385n8BHl44EQes2yvkBgcFNgAJvEd-_4YhaWEZIYMk3vYyzs-CTM3okMcFEDIwjGQI2IP0cyKLBOp2CM1iqD9qkORxRCJNO8zgPt8JJj27w2hsH8XH2oNdjhCfn9TL7-u7tl_1Vfv3p_Yf9q-vc8FbQvDNWl5LasmnrDo1peFlT0L0UkpWdEKIXnazLqrFcStF1vLWGStqXVcVkLRi_zJ6f6i5h_r5CTGpycXu89jCvUTWylQ1qEZQn0IQ5RvyEWoKbdDgqRtWWmTqoLRq1RaO2zNRtZuoGpU_PPdZuAnsnPIeEwLMzoCMagf6gB_GOk2VV86pF7uWJ--FGOP73A9Trj1fbjv8F71G33A</recordid><startdate>200611</startdate><enddate>200611</enddate><creator>Chen, Xiaohua</creator><creator>Hale, Gregory A.</creator><creator>Barfield, Raymond</creator><creator>Benaim, Ely</creator><creator>Leung, Wing H.</creator><creator>Knowles, James</creator><creator>Horwitz, Edwin M.</creator><creator>Woodard, Paul</creator><creator>Kasow, Kimberly</creator><creator>Yusuf, Usman</creator><creator>Behm, Frederick G.</creator><creator>Hayden, Randall T.</creator><creator>Shurtleff, Sheila A.</creator><creator>Turner, Victoria</creator><creator>Srivastava, Deo Kumar</creator><creator>Handgretinger, Rupert</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</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>7X8</scope></search><sort><creationdate>200611</creationdate><title>Rapid immune reconstitution after a reduced‐intensity conditioning regimen and a CD3‐depleted haploidentical stem cell graft for paediatric refractory haematological malignancies</title><author>Chen, Xiaohua ; Hale, Gregory A. ; Barfield, Raymond ; Benaim, Ely ; Leung, Wing H. ; Knowles, James ; Horwitz, Edwin M. ; Woodard, Paul ; Kasow, Kimberly ; Yusuf, Usman ; Behm, Frederick G. ; Hayden, Randall T. ; Shurtleff, Sheila A. ; Turner, Victoria ; Srivastava, Deo Kumar ; Handgretinger, Rupert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3970-bcda280d2695b36563250eaf87812b777f7b85246d3887bb39dc080f244185713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>B-Lymphocytes - immunology</topic><topic>Biological and medical sciences</topic><topic>CD3 Complex - blood</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Graft Survival - immunology</topic><topic>Graft vs Host Disease - immunology</topic><topic>haploidentical haematopoietic stem cell transplantation</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematologic Neoplasms - immunology</topic><topic>Hematologic Neoplasms - therapy</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Humans</topic><topic>immune reconstitution</topic><topic>Killer Cells, Natural - immunology</topic><topic>Lymphocyte Count</topic><topic>Lymphocyte Depletion</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Opportunistic Infections - immunology</topic><topic>Opportunistic Infections - prevention & control</topic><topic>Receptors, Antigen, T-Cell, alpha-beta - analysis</topic><topic>reduced intensity conditioning regimen</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>Transplantation Chimera - immunology</topic><topic>Transplantation Conditioning - methods</topic><topic>T‐cell receptor beta CDR3 size spectratyping</topic><topic>T‐cell receptor excision circle</topic><topic>Viral Load</topic><topic>Viremia - immunology</topic><topic>Viremia - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xiaohua</creatorcontrib><creatorcontrib>Hale, Gregory A.</creatorcontrib><creatorcontrib>Barfield, Raymond</creatorcontrib><creatorcontrib>Benaim, Ely</creatorcontrib><creatorcontrib>Leung, Wing H.</creatorcontrib><creatorcontrib>Knowles, James</creatorcontrib><creatorcontrib>Horwitz, Edwin M.</creatorcontrib><creatorcontrib>Woodard, Paul</creatorcontrib><creatorcontrib>Kasow, Kimberly</creatorcontrib><creatorcontrib>Yusuf, Usman</creatorcontrib><creatorcontrib>Behm, Frederick G.</creatorcontrib><creatorcontrib>Hayden, Randall T.</creatorcontrib><creatorcontrib>Shurtleff, Sheila A.</creatorcontrib><creatorcontrib>Turner, Victoria</creatorcontrib><creatorcontrib>Srivastava, Deo Kumar</creatorcontrib><creatorcontrib>Handgretinger, Rupert</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>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xiaohua</au><au>Hale, Gregory A.</au><au>Barfield, Raymond</au><au>Benaim, Ely</au><au>Leung, Wing H.</au><au>Knowles, James</au><au>Horwitz, Edwin M.</au><au>Woodard, Paul</au><au>Kasow, Kimberly</au><au>Yusuf, Usman</au><au>Behm, Frederick G.</au><au>Hayden, Randall T.</au><au>Shurtleff, Sheila A.</au><au>Turner, Victoria</au><au>Srivastava, Deo Kumar</au><au>Handgretinger, Rupert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid immune reconstitution after a reduced‐intensity conditioning regimen and a CD3‐depleted haploidentical stem cell graft for paediatric refractory haematological malignancies</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2006-11</date><risdate>2006</risdate><volume>135</volume><issue>4</issue><spage>524</spage><epage>532</epage><pages>524-532</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Summary
The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft‐versus‐host disease (GvHD). We designed a reduced‐intensity conditioning regimen that excluded total body irradiation and anti‐thymocyte globulin in order to expedite immune reconstitution after a CD3‐depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3+ T‐cells, T‐cell receptor (TCR) excision circle counts, TCRβ repertoire diversity and natural killer (NK)‐cells during the first 4 months post‐transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well‐tolerated regimen appears to accelerate immune recovery and shorten the duration of early post‐transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T‐cell reconstitution, retention of NK‐cells in the graft and induction of low grade GvHD may also enhance the potential anti‐cancer immune effect.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17010105</pmid><doi>10.1111/j.1365-2141.2006.06330.x</doi><tpages>9</tpages></addata></record> |
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| ispartof | British journal of haematology, 2006-11, Vol.135 (4), p.524-532 |
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| subjects | Adolescent B-Lymphocytes - immunology Biological and medical sciences CD3 Complex - blood Child Child, Preschool Female Flow Cytometry Graft Survival - immunology Graft vs Host Disease - immunology haploidentical haematopoietic stem cell transplantation Hematologic and hematopoietic diseases Hematologic Neoplasms - immunology Hematologic Neoplasms - therapy Hematopoietic Stem Cell Transplantation - methods Humans immune reconstitution Killer Cells, Natural - immunology Lymphocyte Count Lymphocyte Depletion Male Medical sciences Opportunistic Infections - immunology Opportunistic Infections - prevention & control Receptors, Antigen, T-Cell, alpha-beta - analysis reduced intensity conditioning regimen T-Lymphocyte Subsets - immunology Transplantation Chimera - immunology Transplantation Conditioning - methods T‐cell receptor beta CDR3 size spectratyping T‐cell receptor excision circle Viral Load Viremia - immunology Viremia - prevention & control |
| title | Rapid immune reconstitution after a reduced‐intensity conditioning regimen and a CD3‐depleted haploidentical stem cell graft for paediatric refractory haematological malignancies |
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