Thrombocytopenia in acute leukaemia patients treated with IL2: cytolytic effect of LAK cells on megakaryocytic progenitors

Abstract

In vivo administration of recombinant interleukin 2 (IL2) has been associated, in acute leukaemia as well as in other tumours, with a variable degree of thrombocytopenia. In two patients with acute myeloid leukaemia who showed a progressive and severe fall in platelet count during daily continuous i.v. infusion of IL2, we assessed whether peripheral blood IL2-generated lymphokine activated killer (LAK) lymphocytes could affect growth of the autologous bone marrow megakaryocytic progenitor cell compartment (CFU-MK) in vitro. Following overnight pre-incubation in liquid culture of the marrow cells with autologous LAK effectors, there was an almost complete abrogation of the CFU-MK colony growth (97% and 89% inhibition). Pre-incubation in the presence of a monoclonal antibody to tumour necrosis factor alpha (TNF) completely reversed the inhibitory effect. The role played by TNF was confirmed by the finding that recombinant TNF caused a dose-dependent inhibition of the growth of CFU-MK. IL2 alone was ineffective. These results suggest that the often severe thrombocytopenia observed in patients with acute leukaemia treated with IL2 is at least partly due to autologous LAK cells activated in vivo following the administration of IL2.