Cord-blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus-6-associated acute limbic encephalitis: a cohort analysis

Biol Blood Marrow Transplant. 2012 Nov;18(11):1638-48. doi: 10.1016/j.bbmt.2012.04.016. Epub 2012 May 4.

Abstract

Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic hematopoietic stem cell transplantation (HSCT); its most severe manifestation is the syndrome of posttransplantation acute limbic encephalitis (HHV-6-PALE). The epidemiology, risk factors, and characteristics of HHV-6-PALE after unrelated cord-blood transplantation (UCBT) are not well characterized. We analyzed 1344 patients undergoing allogeneic HSCT between March 2003 and March 2010 to identify risk factors and characteristics of HHV-6-PALE. The cohort included 1243 adult-donor HSCT and 101 UCBT recipients. All patients diagnosed with HHV-6-PALE had HHV-6 DNA in cerebrospinal fluid (CSF) specimens in addition to symptoms and studies indicating limbic encephalitis. Nineteen cases (1.4%) of HHV-6-PALE were identified during this study: 10 after UCBT (9.9%) and 9 after adult-donor HSCT (0.7%), for an incidence rate of 1.2 cases/1000 patient-days compared to 0.08 cases/1000 patient-days (P < .001), respectively. Risk factors for HHV-6-PALE on multivariable Cox modeling were UCBT (adjusted hazard ratio [aHR], 20.0; 95% confidence interval [CI], 7.3-55.0; P < .001), time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (aHR, 7.5; 95% CI, 2.8-19.8; P < .001), and adult-mismatched donor (aHR, 4.3; 95% CI, 1.1-17.3; P = .04). Death from HHV-6-PALE occurred in 50% of affected patients undergoing UCBT and no recipients of adult-donor cells. Patients receiving UCBT have increased risk for HHV-6-PALE and greater morbidity from this disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Cohort Studies
  • Cord Blood Stem Cell Transplantation / adverse effects*
  • Female
  • Graft vs Host Disease / cerebrospinal fluid
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / virology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 6, Human / physiology*
  • Humans
  • Limbic Encephalitis / cerebrospinal fluid
  • Limbic Encephalitis / etiology*
  • Limbic Encephalitis / immunology
  • Limbic Encephalitis / virology
  • Male
  • Middle Aged
  • Risk Factors
  • Roseolovirus Infections / cerebrospinal fluid
  • Roseolovirus Infections / etiology*
  • Roseolovirus Infections / immunology
  • Roseolovirus Infections / virology
  • Severity of Illness Index
  • Survival Analysis
  • Transplantation, Homologous
  • Virus Activation