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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-07-1982.
Submitted July 3, 2002
Accepted August 9, 2002
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
Clinical Microbiology & Infectious Diseases, Hadassah University Hospital, Jerusalem, Israel
Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL, USA
Rambam Medical Center, Haifa, Israel
* Corresponding author; email: wolfd{at}md2.huji.ac.il.
Preemptive ganciclovir therapy has reduced the ocurrence of early cytomegalovirus (CMV) disease after hematopoietic stem cell transplantation (HSCT). However, late disease is increasingly reported. We describe two patients who developed late CMV central nervous system (CNS) disease after haploidentical HSCT. Direct genotypic analysis was employed to examine the presence of ganciclovir resistance. One patient had a mixed viral population in the 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 HSCT, 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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