Risk Factors for Human Herpesvirus 6 Reactivation and its Relationship With Syndrome of Inappropriate Antidiuretic Hormone Secretion After Stem Cell Transplantation in Pediatric Patients

Abstract

There have been several reports on the reactivation of human herpesvirus 6 (HHV6) after stem cell transplantation (SCT) in adults, which sometimes induces severe illness. Few reports exist on pediatric patients; therefore, we retrospectively examined HHV6 reactivation after SCT in children. We reviewed 80 patients with a median age of 6 years. We analyzed HHV6 DNA serum samples from the patients before SCT and at 20 and 40 days after SCT using polymerase chain reaction. We also analyzed the relationship between HHV6 reactivation and the syndrome of inappropriate antidiuretic hormone secretion (SIADH). At 20 days after SCT, 35.0% of serum samples were positive for HHV6 DNA. The median viral load was 3.1×10 copies/mL serum. Multivariate analysis showed cord blood transplantation as the only risk factor for HHV6 reactivation. HHV6 reactivation occurs in 59.4% of 32 patients who underwent cord blood transplantation and in 18.8% of 48 patients who underwent SCT from other sources. Among the 14 patients with SIADH, 78.6% experienced HHV6 reactivation. Among the 66 patients without SIADH, only 25.8% had HHV6 reactivation. This result was statistically significant (P<0.001). This analysis revealed that HHV6 reactivation occurs in many children. In addition, HHV6 reactivation plus SIADH should prompt evaluation for central nervous system disease.

Activity of Broad-Spectrum T Cells as Treatment for AdV, EBV, CMV, BKV, and HHV6 Infections after HSCT

“…Whereas even intractable CMV, EBV, and AdV infections have proved to be responsive to adoptive T cell transfer (3)(4)(5)(6)(7)(8)(9)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32), neither BKV nor HHV6, both of which may cause severe and intractable disease in HSCT recipients (33)(34)(35)(36)(37)(38)(39), had previously been targeted using this approach. BKV is a ubiquitous polyomavirus that establishes a latent, asymptomatic infection in >90% of the general population.…”

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

“…[36][37][38] HHV-6 encephalitis may accompany syndrome of inappropriate antidiuretic hormone. [38][39][40] HHV-6 encephalitis typically shows an MRI signature of hyperintense lesions on T2-weighted, fluid-attenuated inversion recovery imaging and diffusion-weighted imaging of bilateral medial temporal lobes, primarily affecting the hippocampus and amygdala (Figure 1). 3,7,[36][37][38]41,42 Some investigators have termed this finding 'post-transplant acute limbic encephalitis (PALE) 38,40,[42][43][44] and HHV-6 PALE has been diagnosed when the patient has detectable HHV-6 DNA in cerebrospinal fluid in the context of acute-onset altered mental status, amnesia, seizures or other evidence of medial temporal lobe disease involving the limbic system and no other identifiable etiology.…”

The preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation

“…38 The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the most de nitely documented pathogenesis of hyponatremia after allo-HSCT 22,38,39 and was reported the association with HHV-6 encephalitis. 20,40,41 Although not all cases had been tested to formally diagnose SIADH in this study, 2 out of 14 patients with HHV-6 encephalitis and 1 out of 120 patients without HHV-6 encephalitis were diagnosed with SIADH. Regarding the timing of hyponatremia and HHV-6 encephalitis, Murakami et al reported that all 5 patients with HHV-6 encephalitis showed hyponatremia on or a few days before the onset.…”