Post-HSCT graft failure due to refractory human cytomegalovirus successfully treated with haploidentical donor-derived immunoglobulins and stem cell graft infusion: A case report
Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality. The incidence of HCMV recurrence in the donor seronegative (D-)/recipient seropositive (R+) group is significantly higher than in other serostatus combinations as a result of a lack of pre-existing...
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description | Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality. The incidence of HCMV recurrence in the donor seronegative (D-)/recipient seropositive (R+) group is significantly higher than in other serostatus combinations as a result of a lack of pre-existing HCMV-specific memory T-lymphocytes in the donor, coupled with the eradication of the recipient's cellular immunity due to the conditioning regimen.
We describe the case of an 8-year-old βE-thalassemic girl from Bangladesh who was seropositive for human cytomegalovirus (HCMV) and underwent hematopoietic stem cell transplantation from a HLA-matched, unrelated, HCMV-seronegative donor. Despite administering antiviral prophylaxis with commercial pooled anti-HCMV immunoglobulin (Ig) from day +1, the post-transplant course was complicated by prompt viral reactivation, and foscarnet therapy was initiated. The virus was refractory to treatment, leading rapidly to complete bone marrow failure, and targeted immunotherapy was proposed as a second-line therapy. Hypothesizing that the patient and her relatives may have been exposed to similar HCMV strains, we selected the patient's mother, who presented a high HCMV antibody titer, as the donor of virus strain-specific anti-HCMV Ig and T-lymphocytes. Complete viral clearance was achieved after two transfusions of the mother's plasma. Subsequently, the patient underwent a haploidentical rescue transplant, promptly reaching full hematological recovery.
These findings suggest that treatment with virus strain-specific Ig may offer a new therapeutic option for critically ill patients.
•Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality.•Reactivation of multiple viral strains is particularly challenging to eradicate. .•Virus strain-specific Ig is an inexpensive, non-toxic therapy to treat HCMV reactivation and improve transplant outcomes. .•The efficacy of this approach as a means of prevention has only been demonstrated previously in mouse models. |
doi_str_mv | 10.1016/j.antiviral.2021.105024 |
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We describe the case of an 8-year-old βE-thalassemic girl from Bangladesh who was seropositive for human cytomegalovirus (HCMV) and underwent hematopoietic stem cell transplantation from a HLA-matched, unrelated, HCMV-seronegative donor. Despite administering antiviral prophylaxis with commercial pooled anti-HCMV immunoglobulin (Ig) from day +1, the post-transplant course was complicated by prompt viral reactivation, and foscarnet therapy was initiated. The virus was refractory to treatment, leading rapidly to complete bone marrow failure, and targeted immunotherapy was proposed as a second-line therapy. Hypothesizing that the patient and her relatives may have been exposed to similar HCMV strains, we selected the patient's mother, who presented a high HCMV antibody titer, as the donor of virus strain-specific anti-HCMV Ig and T-lymphocytes. Complete viral clearance was achieved after two transfusions of the mother's plasma. Subsequently, the patient underwent a haploidentical rescue transplant, promptly reaching full hematological recovery.
These findings suggest that treatment with virus strain-specific Ig may offer a new therapeutic option for critically ill patients.
•Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality.•Reactivation of multiple viral strains is particularly challenging to eradicate. .•Virus strain-specific Ig is an inexpensive, non-toxic therapy to treat HCMV reactivation and improve transplant outcomes. .•The efficacy of this approach as a means of prevention has only been demonstrated previously in mouse models.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2021.105024</identifier><identifier>PMID: 33577809</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Human cytomegalovirus ; Hyperimmune plasma infusion ; Post-transplant graft failure ; Short Communication ; Targeted immunotherapy</subject><ispartof>Antiviral research, 2021-04, Vol.188, p.105024-105024, Article 105024</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.</rights><rights>2021 The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-be04f388b825c54ca4e4f4eace6bc71add0d79da7bef95956da55672585f45ff3</citedby><cites>FETCH-LOGICAL-c475t-be04f388b825c54ca4e4f4eace6bc71add0d79da7bef95956da55672585f45ff3</cites><orcidid>0000-0003-0934-1875</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.antiviral.2021.105024$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33577809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baldo, Francesco</creatorcontrib><creatorcontrib>Suárez, Nicolás M.</creatorcontrib><creatorcontrib>Davison, Andrew J.</creatorcontrib><creatorcontrib>Zanon, Davide</creatorcontrib><creatorcontrib>Barbi, Egidio</creatorcontrib><creatorcontrib>Maximova, Natalia</creatorcontrib><title>Post-HSCT graft failure due to refractory human cytomegalovirus successfully treated with haploidentical donor-derived immunoglobulins and stem cell graft infusion: A case report</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality. The incidence of HCMV recurrence in the donor seronegative (D-)/recipient seropositive (R+) group is significantly higher than in other serostatus combinations as a result of a lack of pre-existing HCMV-specific memory T-lymphocytes in the donor, coupled with the eradication of the recipient's cellular immunity due to the conditioning regimen.
We describe the case of an 8-year-old βE-thalassemic girl from Bangladesh who was seropositive for human cytomegalovirus (HCMV) and underwent hematopoietic stem cell transplantation from a HLA-matched, unrelated, HCMV-seronegative donor. Despite administering antiviral prophylaxis with commercial pooled anti-HCMV immunoglobulin (Ig) from day +1, the post-transplant course was complicated by prompt viral reactivation, and foscarnet therapy was initiated. The virus was refractory to treatment, leading rapidly to complete bone marrow failure, and targeted immunotherapy was proposed as a second-line therapy. Hypothesizing that the patient and her relatives may have been exposed to similar HCMV strains, we selected the patient's mother, who presented a high HCMV antibody titer, as the donor of virus strain-specific anti-HCMV Ig and T-lymphocytes. Complete viral clearance was achieved after two transfusions of the mother's plasma. Subsequently, the patient underwent a haploidentical rescue transplant, promptly reaching full hematological recovery.
These findings suggest that treatment with virus strain-specific Ig may offer a new therapeutic option for critically ill patients.
•Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality.•Reactivation of multiple viral strains is particularly challenging to eradicate. .•Virus strain-specific Ig is an inexpensive, non-toxic therapy to treat HCMV reactivation and improve transplant outcomes. .•The efficacy of this approach as a means of prevention has only been demonstrated previously in mouse models.</description><subject>Human cytomegalovirus</subject><subject>Hyperimmune plasma infusion</subject><subject>Post-transplant graft failure</subject><subject>Short Communication</subject><subject>Targeted immunotherapy</subject><issn>0166-3542</issn><issn>1872-9096</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFUcuOEzEQHCEQGxZ-AXzkMsHjsefBASmKgEVaCSSWs-Wx24kjjx38yCq_xRfiKCGCEydL7eqq6qqqetPgZYOb7t1uKVwyBxOEXRJMmjJlmNAn1aIZelKPeOyeVouC7OqWUXJTvYhxhzHu-nF4Xt20Lev7AY-L6tc3H1N99339gDZB6IS0MDYHQCoDSh4F0EHI5MMRbfMsHJLH5GfYCOuLeo4oZikhRp2tPaIUQCRQ6NGkLdqKvfVGQTEqhUXKOx9qBcEcCsLMc3Z-Y_2UrXERCadQTDAjCdZerBinczTevUcrJEWEYmbvQ3pZPdPCRnh1eW-rH58-Pqzv6vuvn7-sV_e1pD1L9QSY6nYYpoEwyagUFKimICR0k-wboRRW_ahEP4Ee2cg6JRjresIGpinTur2tPpx593maQclySImb74OZRThyLwz_98eZLd_4Ax-bYSAdKwRvLwTB_8wQE59NPN0nHPgcOaHDSDrS0aZA-zNUBh9jCf0q02B-apzv-LVxfmqcnxsvm6__dnnd-1NxAazOAChZHQwEHqUBJ0GZADJx5c1_RX4DFknJEw</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Baldo, Francesco</creator><creator>Suárez, Nicolás M.</creator><creator>Davison, Andrew J.</creator><creator>Zanon, Davide</creator><creator>Barbi, Egidio</creator><creator>Maximova, Natalia</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0934-1875</orcidid></search><sort><creationdate>202104</creationdate><title>Post-HSCT graft failure due to refractory human cytomegalovirus successfully treated with haploidentical donor-derived immunoglobulins and stem cell graft infusion: A case report</title><author>Baldo, Francesco ; Suárez, Nicolás M. ; Davison, Andrew J. ; Zanon, Davide ; Barbi, Egidio ; Maximova, Natalia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-be04f388b825c54ca4e4f4eace6bc71add0d79da7bef95956da55672585f45ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Human cytomegalovirus</topic><topic>Hyperimmune plasma infusion</topic><topic>Post-transplant graft failure</topic><topic>Short Communication</topic><topic>Targeted immunotherapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baldo, Francesco</creatorcontrib><creatorcontrib>Suárez, Nicolás M.</creatorcontrib><creatorcontrib>Davison, Andrew J.</creatorcontrib><creatorcontrib>Zanon, Davide</creatorcontrib><creatorcontrib>Barbi, Egidio</creatorcontrib><creatorcontrib>Maximova, Natalia</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antiviral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baldo, Francesco</au><au>Suárez, Nicolás M.</au><au>Davison, Andrew J.</au><au>Zanon, Davide</au><au>Barbi, Egidio</au><au>Maximova, Natalia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Post-HSCT graft failure due to refractory human cytomegalovirus successfully treated with haploidentical donor-derived immunoglobulins and stem cell graft infusion: A case report</atitle><jtitle>Antiviral research</jtitle><addtitle>Antiviral Res</addtitle><date>2021-04</date><risdate>2021</risdate><volume>188</volume><spage>105024</spage><epage>105024</epage><pages>105024-105024</pages><artnum>105024</artnum><issn>0166-3542</issn><eissn>1872-9096</eissn><abstract>Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality. The incidence of HCMV recurrence in the donor seronegative (D-)/recipient seropositive (R+) group is significantly higher than in other serostatus combinations as a result of a lack of pre-existing HCMV-specific memory T-lymphocytes in the donor, coupled with the eradication of the recipient's cellular immunity due to the conditioning regimen.
We describe the case of an 8-year-old βE-thalassemic girl from Bangladesh who was seropositive for human cytomegalovirus (HCMV) and underwent hematopoietic stem cell transplantation from a HLA-matched, unrelated, HCMV-seronegative donor. Despite administering antiviral prophylaxis with commercial pooled anti-HCMV immunoglobulin (Ig) from day +1, the post-transplant course was complicated by prompt viral reactivation, and foscarnet therapy was initiated. The virus was refractory to treatment, leading rapidly to complete bone marrow failure, and targeted immunotherapy was proposed as a second-line therapy. Hypothesizing that the patient and her relatives may have been exposed to similar HCMV strains, we selected the patient's mother, who presented a high HCMV antibody titer, as the donor of virus strain-specific anti-HCMV Ig and T-lymphocytes. Complete viral clearance was achieved after two transfusions of the mother's plasma. Subsequently, the patient underwent a haploidentical rescue transplant, promptly reaching full hematological recovery.
These findings suggest that treatment with virus strain-specific Ig may offer a new therapeutic option for critically ill patients.
•Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality.•Reactivation of multiple viral strains is particularly challenging to eradicate. .•Virus strain-specific Ig is an inexpensive, non-toxic therapy to treat HCMV reactivation and improve transplant outcomes. .•The efficacy of this approach as a means of prevention has only been demonstrated previously in mouse models.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33577809</pmid><doi>10.1016/j.antiviral.2021.105024</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0934-1875</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Human cytomegalovirus Hyperimmune plasma infusion Post-transplant graft failure Short Communication Targeted immunotherapy |
title | Post-HSCT graft failure due to refractory human cytomegalovirus successfully treated with haploidentical donor-derived immunoglobulins and stem cell graft infusion: A case report |
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