title: Acute graft-versus-host disease after liver transplantation: role of withdrawal of immunosuppression in therapeutic management.
abstract: Graft-versus-host disease (GVHD) after liver transplantation is rare but associated with a very high mortality (over 85%). Most treatments focus on increasing immunosuppression, addition of antibody preparations such as OKT3 and antithymocyte globulin to eliminate the donor lymphocytes, and supporting myelopoiesis by use of cytokines. However, the results are very poor. We reasoned that a better therapeutic approach would be to reduce the immunosuppression and allow the patient's immune system an opportunity to reject the allograft donor T cells. We tested this novel therapeutic approach in 3 patients diagnosed with GVHD. Two patients had rapid loss of donor T cell chimerism and resolution of their symptoms. The other patient continued to progress to severe GVHD and died. The patients who responded to withdrawal of immunosuppression had a later onset of symptoms and a lower level of donor CD3+ T cells at the start of treatment. We conclude that larger studies are needed to further evaluate these results and to determine what factors may affect the likelihood that a patient may respond to this approach.
authors.affiliation: Baylor University Medical Center, Dallas, TX 75246, USA.
authors.forename: Srinath
authors.initials: S
authors.lastname: Chinnakotla
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Smith
authors.forename: Rana
authors.initials: R
authors.lastname: Domiati-Saad
authors.forename: Edward D
authors.initials: ED
authors.lastname: Agura
authors.forename: David L
authors.initials: DL
authors.lastname: Watkins
authors.forename: George
authors.initials: G
authors.lastname: Netto
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Uemura
authors.forename: Edmund Q
authors.initials: EQ
authors.lastname: Sanchez
authors.forename: Marlon F
authors.initials: MF
authors.lastname: Levy
authors.forename: Goran B
authors.initials: GB
authors.lastname: Klintmalm
mesh_terms: D000328:Adult; D001706:Biopsy; D017252:CD3 Complex / Q000096:biosynthesis; D015209:Cholangitis, Sclerosing / Q000601:surgery / Q000628:therapy*; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008107:Liver Diseases / Q000628:therapy*; D016031:Liver Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D007166:Immunosuppressive Agents