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 immunomodu latory 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 acut e myeloid leukemia in remission. At Arhus University Hospital 7 patients we re randomized to receive the active drug and 6 to receive the placebo. Surv iving patients were followed for 2 yr with immunological monitoring of thei r natural immune effector cells (NK- and LAK cell activity). Peripheral hep arinized blood samples were obtained twice before the onset of conditioning therapy and at several time points after ABMT, and whole blood samples wer e analyzed by flow cytometry for the detection of leukocyte differentiation antigens as well as by 4 h Cr-51 release assays for cytotoxicity. In contr ast to previous experience with Linomide, in the present study we found tha t at 36 wk or later time points Linomide patients exhibited a significant s uppression of circulating natural effector cell number and activity when co mpared with the control group. These observations underline the need for fu rther exploration into novel and manageable immunostimulators.