Feb 19, 2002
NEW YORK (Reuters Health)
Since the mid-1990s, several reports have described an association between human herpesvirus 6 (HHV-6) in hematopoietic stem cell transplant recipients and encephalitis. Now, a review at Fred Hutchinson Cancer Research Center concludes that HHV-6 appears to be the cause of the encephalitis, and that antiviral therapy is effective in some cases.
Dr. Danielle M. Zerr and colleagues explain that after publication of the first case reports, they increased surveillance for HHV-6 in stem cell recipients at their center. In their review they identified 11 patients with HHV-6 in cerebrospinal fluid (CSF). Of these, one patient was asymptomatic and 10 presented with encephalopathy or other central nervous system symptoms 12 to 30 days after transplantation.
Two of the 10 patients had concomitant pathologic findings, leaving eight with HHV-6 as the only definable pathogen. Four of those eight died within 1 month of diagnosis, Dr. Zerr's group reports in the February 1st issue of Clinical Infectious Diseases.
All 11 patients received ganciclovir and/or foscarnet. Successive serum and CSF samples were analyzable for six of the eight patients with HHV-6 encephalitis, and in four of these patients the viral load declined. One of the two patients who did not respond was the only patient infected with HHV-6A instead of HHV-6B.
Among the HHV-6 encephalitis patients, abnormal MRI findings and elevated CSF protein levels were more common in those who died soon after diagnosis than in those who survived. Along with the fact that no other pathogens were identified in serum and CSF samples, this implies that HHV-6 damaged the central nervous system, the researchers propose.
When they compared the HHV-6 encephalitis patients with other stem cell recipients at their center, one risk factor for HHV-6 encephalitis was receipt of a transplant from a mismatched or unrelated donor. Such transplants may activate latent HHV-6, the team speculates, or be associated with HHV-6 indirectly, through graft-versus-host disease or the immunosuppressive drugs used to treat it.
Receipt of antithymocyte globulin or the monoclonal anti-CD3 antibody BC3 was also a risk factor. These agents might increase immunosuppression by targeting lymphocytes. Alternatively, these agents may activate latent HHV-6 by activating the targeted lymphocytes, the authors say. A final risk factor was a cord blood transplant, possibly because all cord blood recipients at the center receive antithymocyte globulin.
"We're just beginning to learn about what HHV-6 can do in an immune-compromised state," Dr. Zerr told Reuters Health. "What this report reveals more than anything is that further research is needed to determine what role HHV-6 is playing in these patients who have central nervous system complications, as well as other end-organ disease following bone marrow transplants."
Clin Infect Dis 2002;34:309-317.
© 2002 Reuters Ltd