title: Development of drug-resistant herpes simplex virus infection after haploidentical hematopoietic progenitor cell transplantation.
abstract: An unusually high incidence of acyclovir- and foscarnet-resistant herpes simplex virus (HSV) infection was noted after lymphocyte-depleted blood hematopoietic progenitor cell (HPC) transplantation from HLA-haploidentical family donors. Fourteen adults with hematologic malignancies underwent blood HPC transplantation from haploidentical family donors. Pheresis products were stringently depleted of T and B cells by immunomagnetic adsorption, and patients received no immunosuppression after transplantation. HSV reactivation occurred in all 7 evaluable HSV-1- or HSV-2-seropositive patients, at a median of 40 days after transplantation. Susceptibility testing of clinically resistant viral isolates demonstrated acyclovir resistance in all 5 cases tested. Second-line therapy produced only partial responses, and in vitro evidence of foscarnet resistance developed rapidly in all 3 patients treated with foscarnet. Healing of lesions coincided with T-cell recovery. The prolonged immunodeficiency associated with stringent lymphocyte depletion of the graft appears to strongly predispose to emergence of drug-resistant HSV. Furthermore, immune reconstitution is necessary for eradication of infection.
authors.affiliation: Department of Hematology-Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30302, USA. amelia_langston@emory.org
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Langston
authors.forename: Istvan
authors.initials: I
authors.lastname: Redei
authors.forename: Angela M
authors.initials: AM
authors.lastname: Caliendo
authors.forename: Jyoti
authors.initials: J
authors.lastname: Somani
authors.forename: Don
authors.initials: D
authors.lastname: Hutcherson
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Silvana
authors.initials: S
authors.lastname: Bucur
authors.forename: Judy
authors.initials: J
authors.lastname: Cherry
authors.forename: Andrew
authors.initials: A
authors.lastname: Allen
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral; D005260:Female; D017245:Foscarnet / Q000494:pharmacology; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006561:Herpes Simplex / Q000209:etiology*; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D008212:Lymphocyte Depletion / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D017245:Foscarnet; D000212:Acyclovir