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Antiviral responses following L-leucyl-L-leucine methyl esther (LLME)-treated lymphocyte infusions: graft-versus-infection without graft-versus-host disease. Biol Blood Marrow Transplant 2009 Dec;15(12):1609-19



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-70350459268   7 Citations


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.

Author List

Filicko-O'Hara J, Grosso D, Flomenberg PR, Friedman TM, Brunner J, Drobyski W, Ferber A, Kakhniashvili I, Keever-Taylor C, Mookerjee B, Talano JA, Wagner JI, Korngold R, Flomenberg N


William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Julie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cohort Studies
Flow Cytometry
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Lymphocyte Transfusion
Middle Aged
T-Lymphocyte Subsets
Young Adult