HHV-6 encephalitis can occur in CAR T-cell therapy and biologic immunotherapy

HHV-6 reactivation leading to encephalitis following hematopoietic stem cell transplant (HCST) is well recognized. The 2017 Guidelines from the European Conference on Infections in Leukemia state that it is unlikely in other malignancies and therapies.

Handley et al. of McGovern Medical School UT Health sought to identify whether HHV-6 reactivation and encephalitis might also occur in people with hematologic or non-hematologic malignancies with newer therapies such as chimeric antigen receptor (CAR) T-cell therapy and biologic immunotherapy (checkpoint blockade). They evaluated the medical records of 725 patients who had cerebrospinal fluid tested for HHV-6 DNA with either the Viracor or Biofire® Meningitis Encephalitis Panel platforms and no other identified etiology.

There were 19 cases (2.6 %) of HHV-6-mediated CNS disease.  Most of them, 13/19 (68 %), had undergone HSCT; the median time to encephalitis was 31 days following transplant. Of the 6 who had been treated with CAR-T-cell therapy or biologic immunotherapy, not HSCT, 4 had hematologic malignancies and two had solid tumors (renal carcinoma and melanoma). The most frequent clinical presentation was post-transplant acute limbic encephalitis syndrome (PALE).

 The incidence of HHV-6 encephalitis and PALE are similar to previous studies. In agreement with previous evidence, there was also greater HHV-6 PALE with cord-blood HSCT. The study also revealed a number of instances in which both diagnostic platforms for HHV-6 DNA came to different results, indicating need for improvement of one or both of these assays. Viral load measurements and other evidence indicated that none of the PCR-positive cases were due to inherited chromosomally-integrated HHV-6 (iciHHV-6).

This small study demonstrates that HHV-6 reactivation with subsequent encephalitis does not occur exclusively with HSCT for hematologic malignancies, but also can occur with CAR-T-cell therapy or biologic immunotherapy of both hematologic malignancies and solid tumors—although it remains uncertain how frequently this occurs. 

Read the full article: Handley et al 2021