title: Cord-blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus-6-associated acute limbic encephalitis: a cohort analysis.
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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Hill
authors.forename: Sophia
authors.initials: S
authors.lastname: Koo
authors.forename: Belisa B
authors.initials: BB
authors.lastname: Guzman Suarez
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Marty
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015331:Cohort Studies; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D005260:Female; D006086:Graft vs Host Disease / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000276:immunology / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D020363:Limbic Encephalitis / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019349:Roseolovirus Infections / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000276:immunology / Q000821:virology; D012720:Severity of Illness Index; D016019:Survival Analysis; D014184:Transplantation, Homologous; D014775:Virus Activation