Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity
Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited....
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| Veröffentlicht in: | Journal of clinical immunology 2024-08, Vol.44 (6), p.126-126, Article 126 |
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| creator | Miyamoto, Satoshi Niizato, Daiki Tomomasa, Dan Nishimura, Akira Hoshino, Akihiro Kamiya, Takahiro Isoda, Takeshi Takagi, Masatoshi Kajiwara, Michiko Azumi, Shohei Hirabayashi, Shinsuke Sakamoto, Kenichi Kishimoto, Kenji Miyamura, Takako Umeda, Katsutsugu Hirose, Ayana Keino, Dai Yanagimachi, Masakatsu Kanda, Kaori Sakai, Yuta Ikawa, Yasuhiro Watanabe, Kenichiro Tanaka, Keisuke Mori, Takehiko Ichinohe, Tatsuo Sakaguchi, Hirotoshi Morio, Tomohiro Kanegane, Hirokazu |
| description | Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited. We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months. The donors were haploidentical parents (
n
= 10), matched siblings (
n
= 2), and unrelated bone marrow donors (
n
= 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3–4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4
+
T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238 |
| doi_str_mv | 10.1007/s10875-024-01734-5 |
| format | Article |
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n
= 10), matched siblings (
n
= 2), and unrelated bone marrow donors (
n
= 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3–4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4
+
T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238 < 250 words)</description><identifier>ISSN: 0271-9142</identifier><identifier>ISSN: 1573-2592</identifier><identifier>EISSN: 1573-2592</identifier><identifier>DOI: 10.1007/s10875-024-01734-5</identifier><identifier>PMID: 38773000</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adolescent ; Alemtuzumab - therapeutic use ; Allografts ; Asian People ; Biomedical and Life Sciences ; Biomedicine ; Blood cells ; bone marrow ; Busulfan ; CD4 antigen ; cell transplantation ; Child ; Child, Preschool ; Chimerism ; East Asian People ; excision ; Female ; Fludarabine ; Graft vs Host Disease - etiology ; Graft-versus-host reaction ; Hematopoietic Stem Cell Transplantation - methods ; Hematopoietic stem cells ; Humans ; Immune System Diseases - genetics ; Immunity ; Immunology ; Infant ; Infectious Diseases ; Internal Medicine ; Japan ; Lymphocytes T ; Male ; Medical Microbiology ; Monoclonal antibodies ; Retrospective Studies ; Stem cell transplantation ; T cell receptors ; T-lymphocytes ; Toxicity ; Transplantation Conditioning - methods ; Transplantation, Homologous ; Treatment Outcome ; Viral infections</subject><ispartof>Journal of clinical immunology, 2024-08, Vol.44 (6), p.126-126, Article 126</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c359t-40604c5c53dd3f9d5d343e0971082152644078b182c14d9eeb31ddc54c2764163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10875-024-01734-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10875-024-01734-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38773000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyamoto, Satoshi</creatorcontrib><creatorcontrib>Niizato, Daiki</creatorcontrib><creatorcontrib>Tomomasa, Dan</creatorcontrib><creatorcontrib>Nishimura, Akira</creatorcontrib><creatorcontrib>Hoshino, Akihiro</creatorcontrib><creatorcontrib>Kamiya, Takahiro</creatorcontrib><creatorcontrib>Isoda, Takeshi</creatorcontrib><creatorcontrib>Takagi, Masatoshi</creatorcontrib><creatorcontrib>Kajiwara, Michiko</creatorcontrib><creatorcontrib>Azumi, Shohei</creatorcontrib><creatorcontrib>Hirabayashi, Shinsuke</creatorcontrib><creatorcontrib>Sakamoto, Kenichi</creatorcontrib><creatorcontrib>Kishimoto, Kenji</creatorcontrib><creatorcontrib>Miyamura, Takako</creatorcontrib><creatorcontrib>Umeda, Katsutsugu</creatorcontrib><creatorcontrib>Hirose, Ayana</creatorcontrib><creatorcontrib>Keino, Dai</creatorcontrib><creatorcontrib>Yanagimachi, Masakatsu</creatorcontrib><creatorcontrib>Kanda, Kaori</creatorcontrib><creatorcontrib>Sakai, Yuta</creatorcontrib><creatorcontrib>Ikawa, Yasuhiro</creatorcontrib><creatorcontrib>Watanabe, Kenichiro</creatorcontrib><creatorcontrib>Tanaka, Keisuke</creatorcontrib><creatorcontrib>Mori, Takehiko</creatorcontrib><creatorcontrib>Ichinohe, Tatsuo</creatorcontrib><creatorcontrib>Sakaguchi, Hirotoshi</creatorcontrib><creatorcontrib>Morio, Tomohiro</creatorcontrib><creatorcontrib>Kanegane, Hirokazu</creatorcontrib><title>Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity</title><title>Journal of clinical immunology</title><addtitle>J Clin Immunol</addtitle><addtitle>J Clin Immunol</addtitle><description>Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited. We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months. The donors were haploidentical parents (
n
= 10), matched siblings (
n
= 2), and unrelated bone marrow donors (
n
= 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3–4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4
+
T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238 < 250 words)</description><subject>Adolescent</subject><subject>Alemtuzumab - therapeutic use</subject><subject>Allografts</subject><subject>Asian People</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood cells</subject><subject>bone marrow</subject><subject>Busulfan</subject><subject>CD4 antigen</subject><subject>cell transplantation</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chimerism</subject><subject>East Asian People</subject><subject>excision</subject><subject>Female</subject><subject>Fludarabine</subject><subject>Graft vs Host Disease - etiology</subject><subject>Graft-versus-host reaction</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Hematopoietic stem cells</subject><subject>Humans</subject><subject>Immune System Diseases - genetics</subject><subject>Immunity</subject><subject>Immunology</subject><subject>Infant</subject><subject>Infectious Diseases</subject><subject>Internal Medicine</subject><subject>Japan</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medical Microbiology</subject><subject>Monoclonal antibodies</subject><subject>Retrospective Studies</subject><subject>Stem cell transplantation</subject><subject>T cell receptors</subject><subject>T-lymphocytes</subject><subject>Toxicity</subject><subject>Transplantation Conditioning - methods</subject><subject>Transplantation, Homologous</subject><subject>Treatment Outcome</subject><subject>Viral infections</subject><issn>0271-9142</issn><issn>1573-2592</issn><issn>1573-2592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc1q3DAURkVJaaZpX6CLIMimG7f6u5a1HELaDATaRbIWsqyZKtiSI8mE5Omr6aQNdJGsxEXnfpePg9AnSr5QQuTXTEknoSFMNIRKLhp4g1YUJG8YKHaEVoRJ2igq2DF6n_MtIYS3DN6hY95Jyeu4QvN6HOPOBectvnSTKXGO3pU6WTeO-DqZkOfRhGKKjwHfZB92eD26qSyPy2R67ANeZ28C_lkJF0rG9778wpvQxxTwRUoxZRy3eDNNS_Dl4QN6uzVjdh-f3hN08-3i-vyyufrxfXO-vmosB1UaQVoiLFjgw8C3aoCBC-6IkrUzo8BaIYjsetoxS8WgnOs5HQYLwjLZCtryE_T5kDuneLe4XPTk876TCS4uWXMKvG0VleR1lEDXcgWwR8_-Q2_jkkItsqckVA2KV4odKJtizslt9Zz8ZNKDpkTv1emDOl3V6T_qNNSl06fopZ_c8G_lr6sK8AOQ61fYufR8-4XY38WOowU</recordid><startdate>20240801</startdate><enddate>20240801</enddate><creator>Miyamoto, Satoshi</creator><creator>Niizato, Daiki</creator><creator>Tomomasa, Dan</creator><creator>Nishimura, Akira</creator><creator>Hoshino, Akihiro</creator><creator>Kamiya, Takahiro</creator><creator>Isoda, Takeshi</creator><creator>Takagi, Masatoshi</creator><creator>Kajiwara, Michiko</creator><creator>Azumi, Shohei</creator><creator>Hirabayashi, Shinsuke</creator><creator>Sakamoto, Kenichi</creator><creator>Kishimoto, Kenji</creator><creator>Miyamura, Takako</creator><creator>Umeda, Katsutsugu</creator><creator>Hirose, Ayana</creator><creator>Keino, Dai</creator><creator>Yanagimachi, Masakatsu</creator><creator>Kanda, Kaori</creator><creator>Sakai, Yuta</creator><creator>Ikawa, Yasuhiro</creator><creator>Watanabe, Kenichiro</creator><creator>Tanaka, Keisuke</creator><creator>Mori, Takehiko</creator><creator>Ichinohe, Tatsuo</creator><creator>Sakaguchi, Hirotoshi</creator><creator>Morio, Tomohiro</creator><creator>Kanegane, Hirokazu</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20240801</creationdate><title>Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity</title><author>Miyamoto, Satoshi ; Niizato, Daiki ; Tomomasa, Dan ; Nishimura, Akira ; Hoshino, Akihiro ; Kamiya, Takahiro ; Isoda, Takeshi ; Takagi, Masatoshi ; Kajiwara, Michiko ; Azumi, Shohei ; Hirabayashi, Shinsuke ; Sakamoto, Kenichi ; Kishimoto, Kenji ; Miyamura, Takako ; Umeda, Katsutsugu ; Hirose, Ayana ; Keino, Dai ; Yanagimachi, Masakatsu ; Kanda, Kaori ; Sakai, Yuta ; Ikawa, Yasuhiro ; Watanabe, Kenichiro ; Tanaka, Keisuke ; Mori, Takehiko ; Ichinohe, Tatsuo ; Sakaguchi, Hirotoshi ; Morio, Tomohiro ; Kanegane, Hirokazu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-40604c5c53dd3f9d5d343e0971082152644078b182c14d9eeb31ddc54c2764163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adolescent</topic><topic>Alemtuzumab - therapeutic use</topic><topic>Allografts</topic><topic>Asian People</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood cells</topic><topic>bone marrow</topic><topic>Busulfan</topic><topic>CD4 antigen</topic><topic>cell transplantation</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chimerism</topic><topic>East Asian People</topic><topic>excision</topic><topic>Female</topic><topic>Fludarabine</topic><topic>Graft vs Host Disease - etiology</topic><topic>Graft-versus-host reaction</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Hematopoietic stem cells</topic><topic>Humans</topic><topic>Immune System Diseases - genetics</topic><topic>Immunity</topic><topic>Immunology</topic><topic>Infant</topic><topic>Infectious Diseases</topic><topic>Internal Medicine</topic><topic>Japan</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medical Microbiology</topic><topic>Monoclonal antibodies</topic><topic>Retrospective Studies</topic><topic>Stem cell transplantation</topic><topic>T cell receptors</topic><topic>T-lymphocytes</topic><topic>Toxicity</topic><topic>Transplantation Conditioning - 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We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months. The donors were haploidentical parents (
n
= 10), matched siblings (
n
= 2), and unrelated bone marrow donors (
n
= 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3–4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4
+
T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238 < 250 words)</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38773000</pmid><doi>10.1007/s10875-024-01734-5</doi><tpages>1</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0271-9142 |
| ispartof | Journal of clinical immunology, 2024-08, Vol.44 (6), p.126-126, Article 126 |
| issn | 0271-9142 1573-2592 1573-2592 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3153669170 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adolescent Alemtuzumab - therapeutic use Allografts Asian People Biomedical and Life Sciences Biomedicine Blood cells bone marrow Busulfan CD4 antigen cell transplantation Child Child, Preschool Chimerism East Asian People excision Female Fludarabine Graft vs Host Disease - etiology Graft-versus-host reaction Hematopoietic Stem Cell Transplantation - methods Hematopoietic stem cells Humans Immune System Diseases - genetics Immunity Immunology Infant Infectious Diseases Internal Medicine Japan Lymphocytes T Male Medical Microbiology Monoclonal antibodies Retrospective Studies Stem cell transplantation T cell receptors T-lymphocytes Toxicity Transplantation Conditioning - methods Transplantation, Homologous Treatment Outcome Viral infections |
| title | Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T22%3A44%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Allogeneic%20Hematopoietic%20cell%20Transplantation%20Using%20Alemtuzumab%20in%20Asian%20Patients%20with%20Inborn%20Errors%20of%20Immunity&rft.jtitle=Journal%20of%20clinical%20immunology&rft.au=Miyamoto,%20Satoshi&rft.date=2024-08-01&rft.volume=44&rft.issue=6&rft.spage=126&rft.epage=126&rft.pages=126-126&rft.artnum=126&rft.issn=0271-9142&rft.eissn=1573-2592&rft_id=info:doi/10.1007/s10875-024-01734-5&rft_dat=%3Cproquest_cross%3E3153669170%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3057517393&rft_id=info:pmid/38773000&rfr_iscdi=true |