Recombinant human interleukin 3: Effect on thrombopoiesis in patients with primary and secondary hemopoietic failure

Abstract

Yeast-synthesized recombinant human interleukin 3 (rhIL-3) has been studied in a phase I/II clinical trial initially in patients with normal hemopoietic function (NH). It then was investigated in patients with cytopenias, particularly prolonged secondary hemopoietic failure after chemotherapy and/or radiotherapy (SHF), bone marrow transplantation (BMT), in myelodysplastic syndromes (MDS) and in aplastic anemia (AA). Dose levels ranged from 30–500 μg/m2 daily for 15 days administered as s.c. bolus injection. The clinical results demonstrate the capacity of rhIL-3 to stimulate myelopoiesis in all patient groups (increase in leukocytes in: NH 2.8-fold, SHF 2.9-fold, BMT 6.7-fold, MDS 1.8-fold, AA 1.8-fold) and thrombopoiesis with an increase in platelets in patients with NH (1.9-fold) and SHF (2.7-fold), but to a lesser degree in patients with MDS (1.7-fold in 5/9 patients) after BMT (increase in 1/3 patients) and only rarely in AA (increase in 1/9 patients). A stimulation of erythropoiesis with a rise in reticulocyte counts was observed in 14 of 19 patients with NH, in 6/8 with SHF, in 1/3 after BMT and 4/9 with AA. However, this reticulocyte increase was not, in most cases, followed by a rise in hemoglobin. Thus, rhIL-3 induces a multilineage response and seems to be a promising cytokine to stimulate megakaryopoiesis in patients with thrombocytopenias associated with a variety of underlying diseases.