title: Human herpesvirus-6 encephalitis following allogeneic hematopoietic stem cell transplantation.
abstract: Immunosuppressive monoclonal antibodies directed to immune system cells may reduce rejection and graft versus host disease (GvHD) after allogeneic stem cell transplantation (SCT), but can increase the risks of viral infection. Here, we report human herpes virus-6 (HHV-6) encephalitis despite antiviral prophylaxis in 5 of 43 (11.6%) patients receiving alemtuzumab supported conditioning. Encephalitis occurred at 41-103 days (median 60 days) presenting with confusion in all patients, combined with amnesia (n=3) or seizures (n=2). MRI revealed non-specific white matter changes in two and a non-enhancing medial temporal lobe lesion in three patients. Cerebrospinal fluid (CSF) PCR amplification for HHV-6 was positive in all five patients, (600-2 25 000 (median 4700) copies/ml CSF), while analysis of peripheral blood revealed 100-22 500 (median 1200) viral copies/ml plasma. CSF protein was elevated in four patients, with minimal CSF pleocytosis. Intravenous foscarnet produced neurological improvement at 8-13 (median 11) days and negative plasma PCR at 30-66 (median 50) days. Four patients had complete neurological recovery, but one patient with persistent viral DNA in the CSF succumbed to progressive encephalopathy. Given this high incidence of HHV-6 and the possibility of successful outcome with prompt treatment, a high index of suspicion of this disorder is required in recipients of monoclonal antibody supported allografts.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine and The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: T
authors.initials: T
authors.lastname: Vu
authors.forename: G
authors.initials: G
authors.lastname: Carrum
authors.forename: G
authors.initials: G
authors.lastname: Hutton
authors.forename: H E
authors.initials: HE
authors.lastname: Heslop
authors.forename: M K
authors.initials: MK
authors.lastname: Brenner
authors.forename: R
authors.initials: R
authors.lastname: Kamble
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects*; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D018792:Encephalitis, Viral / Q000209:etiology*; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015654:Herpesvirus 6, Human; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D019349:Roseolovirus Infections / Q000209:etiology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D002556:Cerebrospinal Fluid Proteins; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab