A PHASE I II STUDY OF INTERLEUKIN-3 IN PATIENTS WITH APLASTIC-ANEMIA AND MYELODYSPLASIA/

We performed a phase I/II study of recombinant human interleukin-3 (rh IL-3) in 21 patients with aplastic anemia (AA) or myelodysplasia (MDS) . Patients received 21-day cycles of IL-3 (0.5, 1.25, 2.5, 5.0, or 10 mu g/kg/d) by subcutaneous injection followed by a 10- to 14-day washo ut period. Nineteen patients completed at least one 21-day cycle of IL -3. Frequent toxicities of IL-3 included headache, low-grade fever, an d erythema at the injection site; at higher doses, weight gain and per ipheral edema was seen. Eleven patients developed eosinophilia. Of the 20 evaluable patients, eight had increases in absolute neutrophil cou nts (seven with MDS, one with AA) including six of the nine patients r eceiving greater than or equal to 5.0 mu g/kg/d. One AA patient became transfusion-independent for 8 months, while another AA patient had de creased transfusion requirements. Three patients with MDS had at least a doubling of their platelet count, and another patient experienced a 1.9-fold increase. One patient with RAEB progressed to aleukemic AML by the end of one treatment cycle. IL-3 was well-tolerated, but multil ineage effects were seen in only 25% of patients with primary bone mar row failure states (five of 20 evaluable) and more commonly in patient s with myelodysplastic syndromes. Its optimal use may be as part of co mbination hematopoietic growth factor therapy.