Methods: We identified adult HM patients and HCT recipients treated at Dana-Farber Cancer Institute who developed clinically significant ACV-R HSV disease between 1/1/2006 and 3/1/2018. HCT recipients typically receive 1 year of ACV prophylaxis after HCT, or longer in those with graft-versus-host disease. Clinical, microbiological and treatment details were collected.
Results: Nineteen patients had 27 episodes of ACV-R HSV disease during the study. Median age was 50 years (range 31-77); 15 (79%) were men. Fifteen (79%) were allogeneic HCT recipients and 4 (21%) had HM (3 CLL, 1 NHL). Thirteen (68%) had oral ulcers (HSV1), 4 (21%) had perineal ulcers (3 HSV2, 1 HSV1), 1 had HSV1 vesicles on the trunk and 1 had concurrent oral HSV1 and perineal HSV2 ulcers. Three patients had recurrent ACV-R HSV: two had one recurrence each and one had six recurrences. Of 19 first episodes of ACV-R HSV, 15 (79%) were confirmed by culture-based phenotypic resistance testing.
Most episodes (20/27, 74%) were treated with foscarnet at clinical diagnosis or after failure of high-dose val-ACV; 4 of these episodes were also treated with topical cidofovir without success before foscarnet. Three episodes resolved on high-dose val-ACV or IV ACV alone and 3 were treated with cidofovir or brincidofovir initially. Coinfection was present in 19 episodes (70%), most often bacterial pneumonia or blood stream infection.
Twenty-two episodes (81%) resolved completely after a median of 36 days (range 10-88) of treatment. No patient died of HSV disease but 5 (26%) died before resolution of ACV-R HSV, a median of 25 days (range 1-117) after treatment started. Eight patients died after ACV-R HSV resolved, a median of 111 days (range 27-382) after treatment started. Among HCT recipients, 6 (37%) died within 12 weeks of diagnosis.
Conclusion: ACV-R HSV disease is an uncommon complication of HM and allogeneic HCT. While ACV-resistant HSV did not cause death in this cohort, death within 12 weeks of infection was common.
A. Liakos, None
N. Treister, None
L. R. Baden, None
N. C. Issa, GSK: Investigator , Research grant . Merck: Investigator , Research grant . Akros Pharma: Consultant , Consulting fee .
F. M. Marty, Chimerix: Consultant and Investigator , Consulting fee and Research support .
S. P. Hammond, Merck: Investigator , Research support .
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