Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients.
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.
Wolf
Dana G
DG
Hadassah University Hospital, Jerusalem, Israel. wolfd@md2.huji.ac.il
Lurain
Nell S
NS
Zuckerman
Tsila
T
Hoffman
Ron
R
Satinger
Judith
J
Honigman
Alik
A
Saleh
Niveen
N
Robert
Emanuel S
ES
Rowe
Jacob M
JM
Kra-Oz
Zipora
Z
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
D015774:Ganciclovir