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Human herpesvirus 6-associated limbic encephalitis in adult recipients of unrelated umbilical cord blood transplantation

Bone Marrow Transplantation volume 42, pages 693–695 (2008)Cite this article

Umbilical cord blood transplantation (UCBT) has been shown to be curative in a variety of malignant and non-malignant haematopoietic disorders in children. UCBT has also been offered to adult patients lacking a family or unrelated donor, but with higher rate of transplant-related mortality and infections.1 Human herpesvirus 6 (HHV-6) is a β-herpes virus, which causes exanthema subitum in children. HHV-6 reactivation has been increasingly recognized in allogeneic haematopoietic stem cell transplant recipients, particularly in UCBT where it has been estimated to occur in 87–100% of the cases.2, 3, 4 HHV-6 active infection may cause neurological disorders, which, in UCBT recipients, generally manifest with diffuse brain pathology, mainly involving white matter.5 In allogeneic haematopoietic stem cell transplant adult recipients, HHV-6 has been associated with limbic encephalitis (LE), a CNS disorder confined to the hippocampal regions, which causes anterograde amnesia and epilepsy.6, 7 However, few data are available about this complication among adult UCBT recipients. We retrospectively analysed all consecutive episodes of HHV-6-related CNS involvement in adult (>18 years old) patients receiving UCBT between January 1999 and May 2007 at the Bone Marrow Transplant Unit of Florence. The diagnosis was based on the presence of HHV-6 DNA in cerebrospinal fluid (CSF) once other causes (toxic or infective, including HV1 and HV2, EBV, CMV, BK, JC) of encephalopathy were excluded. PCR was performed according to the protocol of the commercial Herpes Consensus Generic Test (Argene Biosoft, Varilhes, France). Among 15 adult patients receiving UCBT, 2 developed acute neurological symptoms after transplantation; in both the cases, brain magnetic resonance imaging (MRI) and CSF PCR examination were suggestive of a HHV-6-related LE.

Patient 2. A 28-year-old woman affected by AML FAB M6, FLT3 TID positive, with multilineage dysplasia since September 2004, obtained CR after induction chemotherapy. On May 2006, she underwent a double unrelated (4/6 and 5/6 matched) UCBT for a relapse of primary disease. Conditioning regimen consisted of hyperfractionated total body irradiation (1320 cGy), CY and fludarabine. For GvHD prevention, CsA and mycophenolate mofetil were administered. Antimicrobial and CMV prophylaxis (ganciclovir followed by foscarnet and acyclovir) were administered. PMN and platelet engraftment was achieved on days +19 and +45, respectively. Acute skin GvHD grade II was demonstrated by biopsy on day +18, and treated with high-dose prednisone. On day +32, the patient presented with confusion, blurred vision and generalized tonic-clonic seizures, associated with marked hyponatremia suggestive of a syndrome of inappropriate antidiuretic hormone (SIDAH). Plasma levels of CsA were within the therapeutic range. EEG showed bitemporal rhythmic slow waves; brain MRI disclosed hyperintensity areas over both hippocampal regions (Figure 1). The CSF examination revealed slight lymphocyte-predominant pleocytosis of 8 cells/μl, with normal protein (34 mg/100 ml) and glucose (87 mg/100 ml) content. CSF and plasma PCR tested positive for HHV-6 DNA. Chromosomally integrated HHV-6 into DNA from both UBC units was excluded by real-time PCR analysis. Foscarnet (180 mg/kg/day) treatment resulted in a rapid improvement of the neurological symptoms, and the brain MRI images showed an attenuation of hippocampal hyperintensity. A second CSF PCR was negative for viral DNA. The patient died 6 months later for leukaemia relapse.

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Authors and Affiliations

  1. Department of Neurological and Psychiatric Sciences, Azienda Ospedaliero-Universitaria di Careggi, Firenze, Italy

    S Matà, M Moretti & S Sorbi

  2. Department of Hematology, Azienda Ospedaliero- Universitaria di Careggi, Firenze, Italy

    S Guidi, C Nozzoli, L Letizia & A Bosi

  3. Laboratory of Microbiology, Azienda Ospedaliero- Universitaria di Careggi, Firenze, Italy

    A Orsi

  4. Department of Clinical Physiopathology, Radiodiagnostic Section, University of Firenze, Firenze, Italy

    A Pratesi & M Mascalchi

  5. Department of Biomedicine, Laboratory of Immunogenetics, Azienda Ospedaliero-Universitaria di Careggi, Firenze, Italy

    G Rombolà

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Correspondence to S Matà.

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Matà, S., Guidi, S., Nozzoli, C. et al. Human herpesvirus 6-associated limbic encephalitis in adult recipients of unrelated umbilical cord blood transplantation. Bone Marrow Transplant 42, 693–695 (2008). https://doi.org/10.1038/bmt.2008.233

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