EFFECTS OF ANTI-TNF MONOCLONAL-ANTIBODY INFUSION IN PATIENTS WITH HAIRY-CELL LEUKEMIA

Tumour necrosis factor (TNF) can act as an autocrine growth factor for hairy cell leukaemia (HCL) cells. The TNF produced by the malignant clone may also inhibit normal haematopoiesis thereby contributing to the cytopenias observed in patients with the disease. We have studied the effects of infusing a murine monoclonal anti-TNF antibody in three patients with HCL. In two patients receiving 0.5 mg of antibody/kg on alternate days for 12 d, the drug was well tolerated. The third patient received 2 mg/kg on alternate days and developed symptoms of serum sickness by day 9. In two patients with severe B-lymphocytopenia, circulating CD19 and CD20 positive, B-cells were restored to normal, the majority of which were negative for the HCL-associated marker CD11c. B-lymphocyte recovery was associated with a rise in serum immunoreactive IL-6 and with an early rise in immunoreactive TNF. These short courses of anti-TNF MAb treatment had modest effect on the tumour burden, producing a reduction in splenomegaly in one patient. Exploration of the effects of more prolonged administration of higher dose anti-TNF antibody will only be feasible when less immunogenic MAbs are available.