Recombinant human interleukin-3 in refractory severe aplastic anaemia: a phase I/II trial

In a prospective open-labelled phase I/II trial we tested efficacy and tolerability of recombinant human interleukin-3 (rhIL-3) alone in patients with refractory severe aplastic anaemia (SAA). 15 patients with idiopathic (12 patients) or secondary (one post-hepatitic, one drug induced, one dyskeratosis congenita) SAA, refractory or relapsing after one to three courses of antilymphocyte globulin were included. 14 patients were transfusion dependent (RBC 14, platelet 12). RhIL-3 was planned for three patients each at five escalating dose levels of 1, 2, 4, 8 and 16 micrograms/kg, given daily as 24 h continuous infusion for 21 d. RhIL-3 was prematurely withdrawn at days 10 and 11 for adverse events in two patients. 9/15 patients showed an increase in WBC; 2/6 at the 1-2 micrograms/kg and 7/9 at the 4-16 micrograms/kg level, but no sustained effects were seen. No patient showed a response in platelet counts. Additionally, platelet and RBC transfusion requirements were unchanged pre and post study. All patients experienced one or more adverse event, mainly fever (15 patients), bleeding (nine patients), and headache (six patients). Occurrence of adverse events was dose related and the maximum tolerated dose was reached with 8 micrograms/kg. Five patients suffered serious adverse events. RhIL-3 as single growth factor and used alone is of minimal benefit in severe aplastic anaemia.