German HCT specialists call for iciHHV-6 screening of patients and donors

Study finds value in HHV-6 testing of other tissues, as well as blood, and of routine testing for iciHHV-6 in both donors and recipients of allo-HCT.

Investigators from the University of Tuebingen conducted a retrospective analysis of medical records in 689 adult allogeneic HCT recipients over a three year period. Testing for HHV-6 in blood and in other clinical specimens (CSF, BAL fluid, skin biopsies, gastrointestinal biopsies, liver biopsies) was done for clinical reasons (e.g., fever, rash, diarrhea) rather than as part of a systematic study protocol.

HHV-6 infections were identified by several nucleic acid testing procedures in 89 patients. In 85 of the 89, reactivated HHV-6 infection was the cause. The underlying condition was judged to be gastroenteritis (44 cases), pneumonitis (5 cases), dermatitis (2 cases) and encephalitis (1 case): there was no clear organ infection in the remaining cases of reactivated HHV-6 infection revealed by blood testing.

Several findings regarding reactivated HHV-6 infection were of particular interest:

  • Probably because HCT patients were not tested systematically and universally for HHV-6, the rate of HHV-6 reactivation in this study was dramatically lower (12.9%) compared to the rate in other centers that have generally been >50%. This may indicate that the clinicians failed to test for, and therefore failed to identify, many cases of reactivated HHV-6.
  • Among patients with potential HHV-6 organ infection, only 7/53 (13.2%) concomitantly showed HHV-6 positivity in plasma, highlighting the value of viral testing in other tissues as well as blood.
  • The study found a strong correlation between reactivated HHV-6 infection and both acute and chronic graft-versus-host disease: aGVHD (odds ratio [OR]: 3.5378, 95% CI 1.7493– 7.1549; p = .0004) and cGVHD (OR: 2.56, 95% CI 1.4559–4.5363; p = .001). This is consistent with other studies (Hill 2017).

Two findings regarding iciHHV-6 were of particular interest:

  • Four of the 89 cases (4.5% of the positive cases, 0.6% of all 689 subjects) were determined to have iciHHV-6: quantitative PCR of whole blood specimens demonstrated copy numbers ranging from >2X105 to 2.5X106 per ml of blood: consistent with iciHHV-6. This is about what would be expected in the general population in Europe and the US (0.8 – 1%).
  • Of the 4 cases of iciHHV-6, serial studies of viral load before vs. after transplantation determined that 2 involved recipients and 2 involved donors. The small number of iciHHV-6 cases makes it hard to conclude much about the frequency with which iciHHV-6 comes from the donor versus the recipient, except to say that both can occur.

Finally, the investigators propose that the iciHHV-6 status of both patients and donors be determined prior to allogenic hematopoietic cell therapy, in order to facilitate antiviral treatment decisions. They also advise against antiviral treatment in iciHHV-6 patients without relevant clinical symptoms.

Read the full article: Berneking 2022