title: Human chorionic gonadotropin and indolamine 2,3-dioxygenase in patients with GVHD.
abstract: GVHD is a major complication following allogeneic hematopoietic SCT, and is associated with substantial morbidity and mortality. Based on the results of our previous clinical study with females treated with human chorionic gonadotropin (hCG) as preconditioning therapy for in vitro fertilization, we hypothesized that low-dose hCG stimulates indoleamine-2,3-dioxygenase (IDO), IL 10 and regulatory T cells (Treg), thereby suppressing clinical manifestations of chronic GVHD. Active chronic GVHD localized at skin, subcutaneous tissue, joints or gastrointestinal tract that was refractory or intolerant to glucocorticoid therapy improved substantially in 12 of 20 patients treated with hCG for 8 weeks (off-label), enabling a glucocorticoid dose reduction of 28% (average). Twelve of 19 patients with chronic GVHD of the skin responded to hCG therapy with a reduction of 25% (average) in their total skin score. HCG treatment increased IDO expression at median by sevenfold in peripheral mononuclear cells and IL10 levels in serum up to twofold at median from the pretreatment baseline. Further, an expansion of the Treg cell population was measured in one patient, which is also associated with the induction of tolerance. This novel application of low-dose hCG was well tolerated and is of clinical interest for GVHD treatment.
authors.affiliation: Department of Hematology and Oncology, Helios Klinik Schwerin, Schwerin, Germany.
authors.forename: A H
authors.initials: AH
authors.lastname: Elmaagacli
authors.affiliation: Department of Bone Marrow Transplantation (AHE), West German Cancer Center, all University Hospital Essen, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ditschkowski
authors.affiliation: Department of Bone Marrow Transplantation (AHE), West German Cancer Center, all University Hospital Essen, Essen, Germany.
authors.forename: N K
authors.initials: NK
authors.lastname: Steckel
authors.affiliation: Department of Bone Marrow Transplantation (AHE), West German Cancer Center, all University Hospital Essen, Essen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gromke
authors.affiliation: Department of Bone Marrow Transplantation (AHE), West German Cancer Center, all University Hospital Essen, Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Ottinger
authors.affiliation: Department of Dermatology, all University Hospital Essen, Essen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Hillen
authors.affiliation: Institute of Pathology, all University Hospital Essen, Essen, Germany.
authors.forename: H A
authors.initials: HA
authors.lastname: Baba
authors.affiliation: Department of Bone Marrow Transplantation (AHE), West German Cancer Center, all University Hospital Essen, Essen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Trenschel
authors.affiliation: Department of Bone Marrow Transplantation (AHE), West German Cancer Center, all University Hospital Essen, Essen, Germany.
authors.forename: D W
authors.initials: DW
authors.lastname: Beelen
authors.affiliation: Department of Bone Marrow Transplantation (AHE), West German Cancer Center, all University Hospital Essen, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Koldehoff
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D006063:Chorionic Gonadotropin / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000201:enzymology* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D023001:Transplantation Tolerance / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006063:Chorionic Gonadotropin; C508609:IL10 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10