Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report

Cytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Management of refractory CMV infections, especially in developing countries, can be challenging due to the limited availability of second and third-line antiviral drugs or...

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Main Authors: Alejandra Pando-Caciano, Ketty Adid Escudero-Ramirez, Jackeline Carol Rodríguez-Torres, Holger Maita-Malpartida
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-02-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2024.1335969/full
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author Alejandra Pando-Caciano
Ketty Adid Escudero-Ramirez
Jackeline Carol Rodríguez-Torres
Holger Maita-Malpartida
Holger Maita-Malpartida
author_facet Alejandra Pando-Caciano
Ketty Adid Escudero-Ramirez
Jackeline Carol Rodríguez-Torres
Holger Maita-Malpartida
Holger Maita-Malpartida
author_sort Alejandra Pando-Caciano
collection DOAJ
description Cytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Management of refractory CMV infections, especially in developing countries, can be challenging due to the limited availability of second and third-line antiviral drugs or alternative treatments. Here, we present a case of an 8 years-old patient diagnosed with acute myeloid leukemia. Eight months post-diagnosis, the patient underwent TCR-αβ+/CD19+-depleted haploidentical HSCT. Both the donor and recipient tested positive for anti-CMV IgG and negative for IgM antibodies. Before transplantation, the patient received CMV prophylaxis in the form of intravenous ganciclovir. Post-transplantation, the patient exhibited oscillating CMV viral loads and was diagnosed with a refractory infection. Treatment with ganciclovir, foscarnet, and cidofovir was unsuccessful. Sequencing of UL-54 and UL-97 genes was performed to rule out potential resistance to first-line treatment. Ten months after the HSCT, the child died from hypovolemic shock due to gastrointestinal bleeding. This is the first case reported in Peru and Latin America of a refractory CMV infection in a pediatric HSCT recipient without evidence of clinical symptoms and CMV genetic resistance. This case demonstrates the need for alternative treatments to manage refractory CMV infections, especially in haploidentical HSCT cases where drug resistance is frequent (~15%). Furthermore, this case highlights the importance of using highly sensitive genetic tools to detect mutations associated with virus resistance in a broader range of the viral genome.
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spelling doaj-art-5f9c1ff1b9b640dfb4a8b4bb22fda5932025-01-28T04:11:25ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-02-011110.3389/fmed.2024.13359691335969Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case reportAlejandra Pando-Caciano0Ketty Adid Escudero-Ramirez1Jackeline Carol Rodríguez-Torres2Holger Maita-Malpartida3Holger Maita-Malpartida4Department of Cellular and Molecular Sciences, School of Science and Philosophy, Universidad Peruana Cayetano Heredia, Lima, PeruDepartment of Cellular and Molecular Sciences, School of Science and Philosophy, Universidad Peruana Cayetano Heredia, Lima, PeruSub Unidad Integral Especializada del Paciente de Progenitores Hematopoyéticos, Instituto Nacional de Salud del Niño San Borja, Lima, PeruDepartment of Cellular and Molecular Sciences, School of Science and Philosophy, Universidad Peruana Cayetano Heredia, Lima, PeruSub Unidad de Investigación e Innovación Tecnológica, Instituto Nacional de Salud del Niño San Borja, Lima, PeruCytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Management of refractory CMV infections, especially in developing countries, can be challenging due to the limited availability of second and third-line antiviral drugs or alternative treatments. Here, we present a case of an 8 years-old patient diagnosed with acute myeloid leukemia. Eight months post-diagnosis, the patient underwent TCR-αβ+/CD19+-depleted haploidentical HSCT. Both the donor and recipient tested positive for anti-CMV IgG and negative for IgM antibodies. Before transplantation, the patient received CMV prophylaxis in the form of intravenous ganciclovir. Post-transplantation, the patient exhibited oscillating CMV viral loads and was diagnosed with a refractory infection. Treatment with ganciclovir, foscarnet, and cidofovir was unsuccessful. Sequencing of UL-54 and UL-97 genes was performed to rule out potential resistance to first-line treatment. Ten months after the HSCT, the child died from hypovolemic shock due to gastrointestinal bleeding. This is the first case reported in Peru and Latin America of a refractory CMV infection in a pediatric HSCT recipient without evidence of clinical symptoms and CMV genetic resistance. This case demonstrates the need for alternative treatments to manage refractory CMV infections, especially in haploidentical HSCT cases where drug resistance is frequent (~15%). Furthermore, this case highlights the importance of using highly sensitive genetic tools to detect mutations associated with virus resistance in a broader range of the viral genome.https://www.frontiersin.org/articles/10.3389/fmed.2024.1335969/fullHSCTcytomegalovirus infectionantiviral resistanceganciclovirfoscarnetcidofovir
spellingShingle Alejandra Pando-Caciano
Ketty Adid Escudero-Ramirez
Jackeline Carol Rodríguez-Torres
Holger Maita-Malpartida
Holger Maita-Malpartida
Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report
Frontiers in Medicine
HSCT
cytomegalovirus infection
antiviral resistance
ganciclovir
foscarnet
cidofovir
title Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report
title_full Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report
title_fullStr Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report
title_full_unstemmed Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report
title_short Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report
title_sort refractory human cytomegalovirus infection without evidence of genetic resistance in the ul 54 and ul 97 genes in a pediatric hematopoietic stem cell transplant recipient a case report
topic HSCT
cytomegalovirus infection
antiviral resistance
ganciclovir
foscarnet
cidofovir
url https://www.frontiersin.org/articles/10.3389/fmed.2024.1335969/full
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