title: Therapy of sclerodermatous chronic graft-versus-host disease with mammalian target of rapamycin inhibitors.
abstract: This retrospective study analyzes 34 patients with severe sclerodermatous chronic graft-versus-host disease (cGVHD) treated with inhibitors of the mammalian target of rapamycin (mTOR-I). Twelve patients received mTOR-I as monotherapy and 22 a combination therapy. Four patients also received extracorporal photopheresis. mTOR-I were applied as first-line therapy (n = 15) or in refractory disease (n = 19). Drug doses were adjusted to low therapeutical levels (3-8 ng/mL). Six and 20 patients had a complete and a partial response, respectively, with an overall response rate of 76%. Two additional patients had stable disease. Six refractory patients required alternative therapy. Comedication, especially steroids, could be tapered and stopped in a significant number of patients. No difference in response was observed in everolimus- and sirolimus-treated patients. Major adverse events possibly related to mTOR-I were hyperlipidemia and impaired wound healing. Two patients developed thrombotic microangiopathy. Eight patients died, 5 of the nonresponders (cGVHD; n = 3, infection; n = 2) and 3 of the responders (relapse of the underlying malignancy; n = 1, secondary malignancy; n = 1, unknown cause; n = 1). Twenty-six of the 34 patients remain alive, 18 still on therapy with mTOR-I. Median follow-up for surviving patients is 723 days (range 88-1621). The overall survival at 3 years since mTOR-I is 72%. In conclusion, mTOR-I seem to be an effective and well-tolerated treatment option for patients with sclerodermatous cGVHD.
authors.affiliation: Centre for Bone Marrow and Blood Stem Cell Transplantation, Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Jedlickova
authors.forename: Irina
authors.initials: I
authors.lastname: Burlakova
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
authors.forename: Herrad
authors.initials: H
authors.lastname: Baurmann
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: Michael
authors.initials: M
authors.lastname: Schleuning
mesh_terms: D000293:Adolescent; D000328:Adult; D003131:Combined Modality Therapy / Q000379:methods; D000068338:Everolimus; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017893:Photopheresis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013256:Steroids / Q000008:administration & dosage / Q000627:therapeutic use; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D013256:Steroids; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus