Development of drug-resistant herpes simplex virus infection after haploidentical hematopoietic progenitor cell transplantation.
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.
Langston
Amelia A
AA
Department of Hematology-Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30302, USA. amelia_langston@emory.org
Redei
Istvan
I
Caliendo
Angela M
AM
Somani
Jyoti
J
Hutcherson
Don
D
Lonial
Sagar
S
Bucur
Silvana
S
Cherry
Judy
J
Allen
Andrew
A
Waller
Edmund K
EK
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
D000998:Antiviral Agents; D017245:Foscarnet; D000212:Acyclovir