title: Phase I study of alpha-interferon augmentation of cyclosporine-induced graft versus host disease in recipients of autologous bone marrow transplantation.
abstract: To explore the augmentation of cyclosporin-induced graft-versus-host disease (GVHD) in autologous bone marrow transplantation (BMT), we conducted a phase I dose escalation trial of interferon (IFN)-alpha 2a. A dose of either 1 or 3 x 10(6) units of IFN-alpha 2a was given by daily sc injection starting on day 0 of BMT and continuing for 28 days. Cyclosporine (CYA) was also started on day 0 of BMT at a dose of 1 mg/kg/day for 28 days. We enrolled 22 patients (median age 43 years, range 19-55 years, male/female ratio = 9/13) which included 11 patients with lymphoma, 5 patients with Hodgkin's disease, 4 patients with AML and 1 patient each with acute lymphoblastic leukemia (ALL) and myeloma. Patients were divided into four groups: two control groups received either CYA or IFN-alpha 2a alone and the other two groups received IFN-alpha 2a at a dose of either 1 x 10(6) or 3 x 10(6) units/day sc concomitantly with CYA for 28 days. IFN-alpha 2a treatment was terminated early in 5 patients: 2 patients receiving IFN-alpha 2a at a dose of 3 x 10(6) units/day developed intractable fatigue, nausea and vomiting and 3 other patients had life-threatening transplant-related complications not related to IFN-alpha 2a (1 patient receiving 3 x 10(6) units/day, and 2 receiving 1 x 10(6) units/day). These patients were considered not evaluable. Of the 17 evaluable patients, all 13 who received IFN-alpha 2a developed GVHD regardless of whether they received CYA whereas only 2 of the 4 patients who received CYA alone developed detectable GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Wayne State University/Detroit Medical Center, Michigan.
authors.forename: V
authors.initials: V
authors.lastname: Ratanatharathorn
authors.forename: J
authors.initials: J
authors.lastname: Uberti
authors.forename: C
authors.initials: C
authors.lastname: Karanes
authors.forename: L G
authors.initials: LG
authors.lastname: Lum
authors.forename: E
authors.initials: E
authors.lastname: Abella
authors.forename: M E
authors.initials: ME
authors.lastname: Dan
authors.forename: M
authors.initials: M
authors.lastname: Hussein
authors.forename: L L
authors.initials: LL
authors.lastname: Sensenbrenner
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D014182:Transplantation, Autologous
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016572:Cyclosporine