title: Antiviral responses following L-leucyl-L-leucine methyl esther (LLME)-treated lymphocyte infusions: graft-versus-infection without graft-versus-host disease.
abstract: Although allogeneic hematopoietic progenitor cell transplant (HPCT) is curative therapy for many disorders, it is associated with significant morbidity and mortality, which can be related to graft-versus-host disease (GVHD) and the immunosuppressive measures required for its prevention and/or treatment. Whether the immunosuppression is pharmacologic or secondary to graft manipulation, the graft recipient is left at increased risk of the threatening opportunistic infection. Refractory viral diseases in the immunocompromised host have been treated by infusion of virus-specific lymphotyces and by unmanipulated donor lymphocyte infusion (DLI) therapy. L-leucyl-L-leucine methyl ester (LLME) is a compound that induces programmed cell death of natural killer (NK) cells, monocytes, granulocytes, most CD8(+) T cells, and a small fraction of CD4(+) T cells. We have undertaken a study of the use of LLME-treated DLI following T cell-depleted allogeneic HPCT, specifically to aid with immune reconstitution. In this ongoing clinical trial, we have demonstrated the rapid emergence of virus-specific responses following LLME DLI with minimal associated GVHD. This paper examines the pace of immune recovery and the rapid development of antiviral responses in 6 patients who developed viral infections during the time period immediately preceding or coincident with the administration of the LLME DLI.
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. joanne.filicko@jefferson.edu
authors.forename: Joanne
authors.initials: J
authors.lastname: Filicko-O'Hara
authors.forename: Dolores
authors.initials: D
authors.lastname: Grosso
authors.forename: Phyllis R
authors.initials: PR
authors.lastname: Flomenberg
authors.forename: Thea M
authors.initials: TM
authors.lastname: Friedman
authors.forename: Janet
authors.initials: J
authors.lastname: Brunner
authors.forename: William
authors.initials: W
authors.lastname: Drobyski
authors.forename: Andres
authors.initials: A
authors.lastname: Ferber
authors.forename: Irina
authors.initials: I
authors.lastname: Kakhniashvili
authors.forename: Carolyn
authors.initials: C
authors.lastname: Keever-Taylor
authors.forename: Bijoyesh
authors.initials: B
authors.lastname: Mookerjee
authors.forename: Julie-An
authors.initials: JA
authors.lastname: Talano
authors.forename: John I
authors.initials: JI
authors.lastname: Wagner
authors.forename: Robert
authors.initials: R
authors.lastname: Korngold
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004151:Dipeptides / Q000627:therapeutic use*; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D055815:Young Adult
chemical_list: D004151:Dipeptides; C045139:leucyl-leucine-methyl ester