RECOMBINANT HUMAN INTERLEUKIN-3 IN REFRACTORY SEVERE APLASTIC-ANEMIA - 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 pat ients with refractory severe aplastic anaemia (SAA). 15 patients with idiopathic (12 patients) or secondary (one post-hepatitic, one drug in duced, one dyskeratosis congenita) SAA, refractory or relapsing after one to three courses of antilymphocyte globulin were included. 14 pati ents were transfusion dependent (RBC 14, platelet 12). RhIL-3 was plan ned for three patients each at five escalating dose levels of 1, 2, 4, 8 and 16 mu g/kg, given daily as 24h continuous infusion for 21 d. Rh lL-3 was prematurely withdrawn at days 10 and 11 for adverse events in two patients. 9/15 patients showed an increase in WBC: 2/6 at the 1-2 mu g/kg and 7/9 at the 4-16 mu g/kg level, but no sustained effects w ere seen. No patient showed a response in platelet counts. Additionall y, platelet and RBC transfusion requirements were unchanged pre and po st study. All patients experienced one or more adverse event, mainly f ever (15 patients), bleeding (nine patients), and headache (six patien ts). Occurrence of adverse events was dose related and the maximum tol erated dose was reached with 8 mu g/kg. Five patients suffered serious adverse events. RhIL-3 as single growth factor and used alone is of m inimal benefit in severe aplastic anaemia.