roquinimex and Acute-Disease

Topics: Acute Disease; Bone Marrow Transplantation; Graft vs Host Disease; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hydroxyquinolines; Immunotherapy; Interferons; Interleukin-2; Leukemia; Macrophages; T-Lymphocytes

Roquinimex, Linomide, is a quinoline derivative with pleiotropic immunomodulatory activities which has been shown to enhance NK function. As part of a phase III placebo-controlled multicenter study patients were randomized to receive Roquinimex, 0.2 mg/kg body weight, or a placebo twice weekly for a duration of 2 yr following autologous bone marrow transplantation for acute myeloid leukemia in remission. At Arhus University Hospital 7 patients were randomized to receive the active drug and 6 to receive the placebo. Surviving patients were followed for 2 yr with immunological monitoring of their natural immune effector cells (NK- and LAK cell activity). Peripheral heparinized blood samples were obtained twice before the onset of conditioning therapy and at several time points after ABMT, and whole blood samples were analyzed by flow cytometry for the detection of leukocyte differentiation antigens as well as by 4 h 51Cr release assays for cytotoxicity. In contrast to previous experience with Linomide, in the present study we found that at 36 wk or later time points Linomide patients exhibited a significant suppression of circulating natural effector cell number and activity when compared with the control group. These observations underline the need for further exploration into novel and manageable immunostimulators.

Topics: Acute Disease; Adjuvants, Immunologic; Adult; Bone Marrow Transplantation; Cytotoxicity, Immunologic; Female; Humans; Hydroxyquinolines; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Leukemia, Myeloid; Leukocytes; Male; Middle Aged; Transplantation, Autologous; Treatment Outcome

Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses several experimental autoimmune diseases. Here we report the effects of Linomide on experimental autoimmune encephalomyelitis (EAE), a CD4+ T cell-mediated animal model of multiple sclerosis (MS). EAE induced in Lewis rats by inoculation with homogenized guinea pig spinal cord and Freund's complete adjuvant was strongly suppressed by Linomide administered daily subcutaneously from the day of inoculation. Linomide dose-dependently delayed the interval between immunization and onset of clinical EAE, and reduced severity of EAE symptoms. These clinical effects were associated with dose-dependent down-modulation of myelin antigens-induced T cell responses and by suppression of the proinflammatory cytokines IFN-gamma and TNF-alpha, and upregulation IL-4, IL-10 and TGF-beta as evaluated by in situ hybridization for mRNA expression in spleen mononuclear cells and spinal cord sections. These findings suggest that Linomide could be useful in certain T cell dependent autoimmune diseases.

Topics: Acute Disease; Adjuvants, Immunologic; Animals; Cytokines; Dose-Response Relationship, Drug; Encephalomyelitis, Autoimmune, Experimental; Histocompatibility Antigens Class II; Hydroxyquinolines; Immunohistochemistry; Male; Rats; Rats, Inbred Lew; RNA, Messenger; T-Lymphocytes

Roquinimex is being used for posttransplantation immunotherapy of autologous bone marrow transplantation for acute and chronic myelogenous leukemia. This immunotherapeutic agent is a cytokine inducer and may induce an autologous graft-versus-host (GVH) and graft-versus-tumor reactions.. Our purpose was to examine patients undergoing this immunotherapy for clinical signs and symptoms of acute GVH reactions and to correlate these symptoms with their clinical outcome.. We studied eight patients receiving requinimex therapy.. We found autologous GVH reactions in three of eight patients (38%) treated with this immunotherapy. Their disease was manifested by localized or widespread violaceous papules that on histologic evaluation were compatible with a grade II GVH reaction. The acute cutaneous GVH reaction was associated with eccrine sweat gland necrosis, a dermatologic toxicity usually associated with chemotherapy.. Long-term studies of larger numbers of patients treated with this immunotherapy will determine whether these GVH reactions confer significant, sustained, antitumor effects.

Topics: Acute Disease; Adjuvants, Immunologic; Bone Marrow Transplantation; Female; Graft vs Host Reaction; Humans; Hydroxyquinolines; Leukemia, Myeloid; Male; Middle Aged; Necrosis; Skin; Skin Diseases; Sweat Glands; Transplantation, Autologous