HHV-6 found to cause 35% of CNS infections in allo-HSCT transplantation

In All, CNS Disease, Transplant Complications by Kristin Loomis

A retrospective analysis out of the Tokyo Metropolitan Cancer and Infectious Diseases Center reviewed 353 consecutive adult allogeneic hematopoietic stem cell transplant (allo-HSCT) cases and identified 17 cases of CNS infection post-transplant. As determined by PCR on cerebrospinal fluid, HHV-6 was found to be the causative agent in 6 cases, or 1.7% of all transplants. The authors also evaluated the cases to characterize the courses of infection. Other pathogens that caused the CNS infections post-transplant were enterococcus (n = 2), staphylococcus (n = 2), streptococcus (n = 2), varicella zoster virus (n = 1), cytomegalovirus, John Cunningham virus (n = 1), adenovirus (n = 1), and Toxoplasma gondii (n=1), but as the causative agent in 35% of the CNS infections, HHV-6 was found at the highest rate.

All 6 patients with HHV-6-associated CNS infection post-transplant were diagnosed with meningoencephalitis. The stem cell source in 2 patients was cord blood, and the rate of HHV-6-associated CNS infection after cord blood transplantation was 4.5%. Five of the six patients (83%) died within a year after the onset of the meningoencephalitis, including the 2 who had undergone cord blood transplants as well as 3 who had undergone unrelated bone marrow transplants. The single patient who survived had received stem cells from a related bone marrow source. These statistics are in line with previous reports that have found cord blood stem cells and unrelated stem cells to be risk factors for HHV-6 reactivation and encephalitis in transplant patients (Ogata 2015, Zerr 2005, Zerr 2011).  When taking into account all of the patients with CNS infections, the overall survival at 3 years after allo-HSCT was 33%. Those without any CNS infection had a survival rate of 53%.

HHV-6 reactivated between 2 and 7 weeks after transplantation, and 3 of the HHV-6 positive patients had been treated with steroids as part of GVHD prophylactic treatment. Steroid use has been associated with HHV-6 reactivation in transplant patients (Ogata 2006). During the reactivation, half of the group presented with lesions in the medial temporal lobe, while the other half had normal MRIs. All showed altered mental status, but only one had convulsions. Although everyone in the cohort was treated with foscarnet, outcomes were highly unfavorable. Five patients improved under treatment, but persistent disturbance of consciousness, persistent disorientation, and persistent memory impairment were observed. Of those who died, one developed sepsis, one died of disease progression (acute myeloid leukemia), one had an unknown cause of death, and two developed pneumonia. The patient who survived suffered from persistent memory impairment. Debilitating sequelae are common in survivors of post-transplant encephalitis (Sakai 2011).

This study reinforces the considerable potential for HHV-6 reactivation after allo-HSCT transplantation to cause very serious CNS infections and adds to an ever-growing knowledge base on the characteristics of HHV-6 reactivation in transplant patients. In addition, the authors found HHV-6 to be the most common cause of CNS infection post-allo-HSCT-transplant, underlining the need to monitor transplant patients for HHV-6 reactivation. Prophylactic antiviral treatment has been suggested for patients at risk of HHV-6 reactivation and is currently under study, although treatment would carry with it a different set of risks associated with side effects from the drugs (Ogata 2015). The development of new safe, effective HHV-6-specific antivirals could have a great impact on at-risk transplant patients who would benefit from prophylaxis.

To read more about HHV-6 encephalitis in transplant patients, visit our page on the topic.

The full paper can be found here: Hanajiri 2016.