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 haploidentica...

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Bibliographic Details
Published in:	Blood Vol. 101; no. 2; pp. 463 - 465
Main Authors:	Wolf, Dana G., Lurain, Nell S., Zuckerman, Tsila, Hoffman, Ron, Satinger, Judith, Honigman, Alik, Saleh, Niveen, Robert, Emanuel S., Rowe, Jacob M., Kra-Oz, Zipora
Format:	Journal Article
Language:	English
Published:	Washington, DC Elsevier Inc 15-01-2003 The Americain Society of Hematology
Subjects:	Adult Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Biological and medical sciences Bone marrow, stem cells transplantation. Graft versus host reaction Central Nervous System Viral Diseases - drug therapy Central Nervous System Viral Diseases - etiology Cytomegalovirus - classification Cytomegalovirus - genetics Cytomegalovirus Infections - drug therapy Cytomegalovirus Infections - etiology Drug Resistance - genetics Female Ganciclovir - therapeutic use Hematologic and hematopoietic diseases Hematopoietic Stem Cell Transplantation - adverse effects Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Mutation Time Factors Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation, Homologous - adverse effects Human Cytomegalovirus Opportunistic infection Late Herpesviridae Stem cell Hematopoietic cell Homograft Recipient Betaherpesvirinae Infection Virus Viral disease Emergence Central nervous system disease Graft
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Summary:	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 mutantUL97 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood-2002-07-1982