Recombinant human interleukin-3 (rH IL-3) in combination with remission induction chemotherapy in patients with relapsed acute myelogenous leukemia (AML): A phase I/II study

Patients with AML who relapse after an initial remission, have a poor prognosis. Administration of hemopoietic growth factors (HGFs) such as interleukin-3 (IL-3) during chemotherapy may result in an increased cell kill by cytotoxic agents. In addition, administration of IL-3 following chemotherapy may potentially accelerate hemopoietic recovery from chemotherapy-induced bone marrow hypoplasia. We performed an open labelled, phase I/II study in which patients received IL-3 by continuous infusion from 24 h before the beginning of chemotherapy until day 28. Chemotherapy included daunorubicin or mitoxantrone days 1-3 and cytarabine 200 mg/m(2) days 1-7. IL-3 was given at a dose of 5 mu g/kg/day in 10 patients, 7.5 mu g/kg/day in six patients and 10 mu g/kg/day in four patients. Complete remissions (CR) after one cycle of this treatment were obtained in 5/10 patients in the 5 mu g/kg group, 2/6 in the 7.5 mu g/kg group and 3/4 in the 10 mu g/kg group). Thus, 50% (10/20) of all individuals and 45% (5/11) of the elderly patients attained CR. Eight of 20 patients entered PR, and 2/20 patients died during the hypoplastic phase from infectious complications. Neutrophils and platelets recovered to 0.5 x 10(9)/l at day 25 (median) and to 50 x 10(9)/l at day 32, respectively. Adverse events during IL-3 and concomitant chemotherapy were fluid retention (4/20), rash (14/20), bone pain (2/20), headache (10/20), chest pain (1/20), arthritis (1/20), fever and nausea. IL-3 (at the dose of 10 mu g/kg) was discontinued in two patients because of side-effects (fluid retention, fever, rash and chest pain), and in two other patients the high IL-3 dose was tolerated with no problems for 29 days. Thus, IL-3 applied to patients with high-risk AML at dosages of 5-10 mu g/kg is tolerated with acceptable toxicity and results in a satisfactory frequency of complete responses following a single treatment cycle.