Risk Factors for Developing Human Herpes Virus-6 Encephalitis and Clinical Significance of Antiviral Therapy In Early Phase After Allogeneic Hematopoietic Stem Cell Transplantation.

Human herpes virus-6 (HHV-6) encephalitis is a relatively rare complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, the patients who developed HHV-6 encephalitis sometimes might be serious condition and suffer the consequences such as a disturbance of memory. We studied the viral load of HHV-6 after HSCT and evaluated risk factors of encephalitis, and assessed the clinical significance of antiviral therapy in early phase after HSCT for the prevention of HHV-6 encephalitis.

The viral load of HHV-6 by PCR was measured at 2, 3, and 4 weeks following HSCT for acute leukemia or myelodysplastic syndromes between April 2004 and May 2010. HHV-6 encephalitis was diagnosed with neurologic symptoms, the elevation of viral load in CSF, and abnormal MR imaging findings. Patients were divided into 2 groups based on the administration of antiviral agents (ganciclovir, valganciclovir or foscarnet) within 28 days after HSCT. Patients who had no treatment with antiviral agents until the development of HHV-6 encephalitis were defined as group A (n=96). Patients who received preemptive therapy within 28 days for the elevation of viral overload of HHV-6 or cytomegalovirus antigenemia, or other reason were defined as group B (n=34).

A total of 130 patients included 79 with acute myeloid leukemia (AML), 34 with acute lymphoid leukemia (ALL), and 17 with myelodysplastic syndrome (MDS).The median age was 41 years (range, 17–65). There were 66 males and 64 females. A disease risk at the time of transplant indicated a standard risk in 76 patients and a high risk in 54. Myeloablative conditioning was employed for 78 patients and reduced intensity conditioning was for 52. Bone marrow transplantation (BMT) from related donor, BMT from unrelated donor, peripheral blood stem cell transplantation from related donor, and cord blood transplantation were done for 39, 53, 12 and 26 patients, respectively. The median level of viral load at 2, 3, and 4 weeks after HSCT were 0 (range, 0–41200) (n=130), 0 (0-290000) (n=125), and 0 (0-3650) (n=114) copies/ml, respectively. Eight patients developed HHV-6 encephalitis in group A. Five of the eight patients with encephalitis had undergone UBMT and 3 had received CBT. The median age was 35 years (range, 22–59), 4 were male. Two patients had received the second HSCT for leukemia relapse. The median day from HSCT to diagnosis was 17.5 days (range, 15–26). The median of viral load was 6630 (range, 1610–22100) copies/ml at diagnosis. All patients received antiviral therapy either ganciclovir or foscarnet. Three of the 8 patients died on day 97 (sepsis), 160 (viral pneumonia), and 346 (chronic GVHD), respectively. Two of the five surviving patients have been suffering from short term memory deficit. By univariate analysis in group A, risk factors for developing HHV-6 encephalitis were unrelated donor (vs related donor: 14.8 vs 0%, p<0.01), ALL (vs AML and MDS: 19.2% vs 4.2%, p=0.03), fever³38°C within 6 days after HSCT (vs fever< 38°C: 29.6 vs 0%, p<0.01), use of corticosteroid within 3 weeks after HSCT (vs no use: 45.5 vs 3.5%, p<0.01), and positive for viral load at 2 weeks after HSCT (vs negative: 27.3% vs 2.7%, p<0.01). The median time of starting preemptive antiviral therapy with either ganciclovir, valganciclovir or foscarnet in group B was day 20 (range, 11–28) after HSCT. No patients developed HHV-6 encephalitis in group B, although there was no significant difference of patient characteristics between group A and B.

HHV-6 encephalitis occurring after HSCT is becoming a curable complication, but its sequelae such as neuropsychological disorders have a marked influence on the quality of life. Preemptive antiviral therapy for patients with risk factors and the elevation of viral load on day 14 might be a potential strategy for preventing of HHV-6 encephalitis.

No relevant conflicts of interest to declare.