Phase I study of alpha-interferon augmentation of cyclosporine-induced graft versus host disease in recipients of autologous bone marrow transplantation

• Published in: Bone marrow transplantation (Basingstoke) Vol. 13; no. 5; p. 625
• Main Authors: Ratanatharathorn, V, Uberti, J, Karanes, C, Lum, L G, Abella, E, Dan, M E, Hussein, M, Sensenbrenner, L L
• Format: Journal Article
• Language: English
• Published: England 01-05-1994
• Subjects: Adult; Bone Marrow Transplantation - immunology; Cyclosporine - adverse effects; Cyclosporine - therapeutic use; Female; Graft vs Host Disease - chemically induced; Humans; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Male; Middle Aged; Recombinant Proteins; Transplantation, Autologous
• ISSN: 0268-3369

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.