Natural effector cells in patients with acute myeloid leukemia treated with the immunomodulator Linomide after autologous bone marrow transplantation.
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.
Hokland
M
M
Institute of Medical Microbiology and Immunology, University of Aarhus, Denmark. hokland@gjallar.daimi.aau.dk
Jørgensen
H
H
Holm
M S
MS
Simonsson
B
B
Nilsson
B
B
Bengtsson
M
M
Hokland
P
P
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects*; D007951:Leukemia, Myeloid / Q000628:therapy*; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; C045282:roquinimex