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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

Date

09/12/2009

Pubmed ID

19744572

Pubmed Central ID

PMC2783272

DOI

10.1016/j.bbmt.2009.08.020

Scopus ID

2-s2.0-70350459268   7 Citations

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.

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

Authors

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

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