Case report: persistent cytomegalovirus (CMV) infection after haploidentical hematopoietic stem cell transplantation using in vivo alemtuzumab: emergence of resistant CMV due to mutations in the UL97 and UL54 genes

Journal of Medical Virology
Kumi OshimaMineo Kurokawa

Abstract

Addition of in vivo alemtuzumab to the conditioning regimen enabled 2- or 3-locus-mismatched hematopoietic stem cell transplantation with an acceptable incidence of graft-versus-host-disease. However, the procedure was associated with a high incidence of cytomegalovirus (CMV) reactivation. Although preemptive therapy with ganciclovir prevented successfully severe CMV diseases and CMV-related mortality, a patient developed persistent positive CMV antigenemia for more than 1 year after transplantation and CMV disease, despite the use of ganciclovir and foscarnet. The in vitro susceptibility assay showed that the clinical isolate was resistant to foscarnet, moderately resistant to ganciclovir, but sensitive to cidofovir. Therefore, cidofovir was administered. CMV antigenemia became negative within 2 weeks and never developed again. Nucleotide sequence of the UL54 and UL97 of the clinical isolate showed 4 amino acid substitutions (V11L, Q578H, S655L, and G874R) in UL54 and 2 mutations (A140V and A594V) in UL97 compared with the Towne and AD169 strains. Ganciclovir resistance was suspected to be caused by both A594V of UL97 and Q578H of UL54, whereas foscarnet resistance was due mainly to Q578H of UL54. In conclusion, the in vitro s...Continue Reading

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Citations

Feb 8, 2011·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Sunwen Chou
Aug 3, 2010·Infectious Disease Clinics of North America·Lynne Strasfeld, Sunwen Chou
May 15, 2010·Infectious Disease Clinics of North America·Lynne Strasfeld, Sunwen Chou
Dec 18, 2015·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Marco HerlingVeronica Di Cristanziano
Oct 27, 2009·Antiviral Research·Meike ChevillotteThomas Mertens
Jun 25, 2009·Seminars in Hematology·Timothy Jancel, Scott R Penzak
Jul 16, 2015·Cellular and Molecular Life Sciences : CMLS·Miriam CiáurrizNatalia Ramírez
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Mar 3, 2010·The Journal of Pharmacology and Experimental Therapeutics·Takashi KuramotoKimiyasu Shiraki

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