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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-07-1982.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 463-465
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Brief report
Emergence of late cytomegalovirus central nervous system disease
in hematopoietic stem cell transplant recipients
Dana G. Wolf,
Nell S. Lurain,
Tsila Zuckerman,
Ron Hoffman,
Judith Satinger,
Alik Honigman,
Niveen Saleh,
Emanuel S. Robert,
Jacob M. Rowe, and
Zipora Kra-Oz
From the Hadassah University Hospital, Jerusalem,
Israel; Rush-Presbyterian-St Luke's Medical Center,
Chicago, IL; Rambam Medical Center, Haifa, Israel.
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.
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