A phase I trial of recombinant human interleukin-6 in patients with myelodysplastic syndromes and thrombocytopenia Journal Article

Authors: Gordon, M. S.; Nemunaitis, J.; Hoffman, R.; Paquette, R. L.; Rosenfeld, C.; Manfreda, S.; Isaacs, R.; Nimer, S. D.
Article Title: A phase I trial of recombinant human interleukin-6 in patients with myelodysplastic syndromes and thrombocytopenia
Abstract: To evaluate the hematologic effects of recombinant human interleukin-6 (rhIL-6, Escherichia coli, SDZ ILS 969, IL-6), and determine its toxicity profile, we performed a phase I trial of IL-6 in 22 patients with various myelodysplastic syndromes (MDS), platelet counts <100,000/mu L, and <5% bone marrow (BM) blasts. Patients received one of four doses of IL-6 (1.0, 2.5, 3.75, and 5.0 mu g/kg/d) as a subcutaneous injection on day 1, followed by a 7-day wash-out period, and then 28 days of IL-6 therapy. Dose-limiting toxicities of fatigue, fever, and elevated alkaline phosphatase were seen at 5.0 mu g/kg/d; the maximum tolerated dose was 3.75 mu g/kg/d. All patients experienced at least grade II fever and all had an increase in acute phase proteins, Eight patients (36%) experienced at least a transient improvement in platelet counts: three fulfilled the criteria for response, whereas five others had clinically significant increases that failed to meet response criteria. Various IL-6-related toxicities prevented more than three patients from receiving maintenance therapy. Two of the three patients who received maintenance IL-6 therapy had a persistent increase in platelet counts, during 3 and 12 months of IL-6 therapy, respectively, Laboratory studies indicated that IL-6 increased the frequency of higher ploidy megakaryocytes but did not significantly increase the number of assayable megakaryocytic progenitor cells, suggesting that IL-6 acts as a maturational agent rather than a megakaryocyte colony-stimulating factor. Although IL-6 therapy can promote thrombopoiesis in some MDS patients, its limited activity and significant therapy-related toxicity preclude its use as a single agent in this patient population, Further studies, combining low doses of IL-6 with other hematopoietic growth factors, are underway. (C) 1995 by The American Society of Hematology.
Keywords: leukemia; colony-stimulating factor; progenitor cells; primates; invivo; bone-marrow transplantation; hematopoietic progenitors; lymphocytes-t; 13-cis retinoic acid; megakaryocytopoiesis; invitro human
Journal Title: Blood
Volume: 85
Issue: 11
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1995-06-01
Start Page: 3066
End Page: 3076
Language: English
ACCESSION: WOS:A1995RA13600008
PUBMED: 7538815
Notes: Article -- Source: Wos