title: Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients.
abstract: Preemptive ganciclovir therapy has reduced the occurrence of early cytomegalovirus (CMV) disease after hematopoietic stem cell (HSC) transplantation. However, late disease is increasingly reported. We describe 2 patients who developed late CMV central nervous system (CNS) disease after haploidentical HSC transplantation. Direct genotypic analysis was used to examine the presence of ganciclovir resistance. One patient had a mixed viral population in the cerebrospinal fluid (CSF), with coexistent wild-type and mutant UL97 sequences. The presence of 2 different strains was confirmed by subclone sequencing of the UL54 gene. One of the strains was different from the concurrent blood strain. The second patient had resistant variant in the lungs. These cases raise concern about the changing natural history of CMV disease in HSC transplantation, with emergence of previously uncommon manifestations following prolonged prophylaxis. Under these circumstances the CNS may be a sanctuary site, where viral persistence and antiviral drug resistance could result from limited drug penetration.
authors.affiliation: Hadassah University Hospital, Jerusalem, Israel. wolfd@md2.huji.ac.il
authors.forename: Dana G
authors.initials: DG
authors.lastname: Wolf
authors.forename: Nell S
authors.initials: NS
authors.lastname: Lurain
authors.forename: Tsila
authors.initials: T
authors.lastname: Zuckerman
authors.forename: Ron
authors.initials: R
authors.lastname: Hoffman
authors.forename: Judith
authors.initials: J
authors.lastname: Satinger
authors.forename: Alik
authors.initials: A
authors.lastname: Honigman
authors.forename: Niveen
authors.initials: N
authors.lastname: Saleh
authors.forename: Emanuel S
authors.initials: ES
authors.lastname: Robert
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Zipora
authors.initials: Z
authors.lastname: Kra-Oz
mesh_terms: D000328:Adult; D020805:Central Nervous System Viral Diseases / Q000188:drug therapy / Q000209:etiology*; D003587:Cytomegalovirus / Q000145:classification / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000209:etiology*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D015774:Ganciclovir