|
|
 Previous Article | Table of Contents | Next Article 
A phase I trial of recombinant human interleukin-6 in patients with
myelodysplastic syndromes and thrombocytopenia
MS Gordon, J Nemunaitis, R Hoffman, RL Paquette, C Rosenfeld, S Manfreda, R Isaacs and SD Nimer
Department of Medicine, Indiana University School of Medicine,
Indianapolis, USA.
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/microL, and
< 5% bone marrow (BM) blasts. Patients received one of four doses of
IL-6 (1.0, 2.5, 3.75, and 5.0 micrograms/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 micrograms/kg/d; the maximum tolerated dose
was 3.75 micrograms/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.
Volume 85,
Issue 11,
pp. 3066-3076,
06/01/1995
Copyright © 1995 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Kurzrock
Thrombopoietic Factors in Chronic Bone Marrow Failure States: The Platelet Problem Revisited
Clin. Cancer Res.,
February 15, 2005;
11(4):
1361 - 1367.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Messmann, C. D. Ullmann, T. Lahusen, A. Kalehua, J. Wasfy, G. Melillo, I. Ding, D. Headlee, W. D. Figg, E. A. Sausville, et al.
Flavopiridol-related Proinflammatory Syndrome Is Associated with Induction of Interleukin-6
Clin. Cancer Res.,
February 1, 2003;
9(2):
562 - 570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Kuter and C. G. Begley
Recombinant human thrombopoietin: basic biology and evaluation of clinical studies
Blood,
November 15, 2002;
100(10):
3457 - 3469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. F. List
New Approaches to the Treatment of Myelodysplasia
Oncologist,
April 1, 2002;
7(90001):
39 - 49.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kurzrock, J. Cortes, D. A. Thomas, S. Jeha, S. Pilat, and M. Talpaz
Pilot Study of Low-Dose Interleukin-11 in Patients With Bone Marrow Failure
J. Clin. Oncol.,
November 1, 2001;
19(21):
4165 - 4172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kaser, G. Brandacher, W. Steurer, S. Kaser, F. A. Offner, H. Zoller, I. Theurl, W. Widder, C. Molnar, O. Ludwiczek, et al.
Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis
Blood,
November 1, 2001;
98(9):
2720 - 2725.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. D. Demetri
Targeted Approaches for the Treatment of Thrombocytopenia
Oncologist,
October 1, 2001;
6(2008):
15 - 23.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Cobankara, B. Oran, D. Ozatli, I. C. Haznedaroglu, A. Kosar, Y. Buyukasik, O. Ozcebe, S. Dundar, and S. Kirazli
Cytokines, Endothelium, and Adhesive Molecules in Pathologic Thrombopoiesis
Clinical and Applied Thrombosis/Hemostasis,
April 1, 2001;
7(2):
126 - 130.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. L. Heaney and D. W. Golde
Myelodysplasia
N. Engl. J. Med.,
May 27, 1999;
340(21):
1649 - 1660.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Späth-Schwalbe, K. Hansen, F. Schmidt, H. Schrezenmeier, L. Marshall, K. Burger, H. L. Fehm, and J. Born
Acute Effects of Recombinant Human Interleukin-6 on Endocrine and Central Nervous Sleep Functions in Healthy Men
J. Clin. Endocrinol. Metab.,
May 1, 1998;
83(5):
1573 - 1579.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Z. Ratajczak, J. Ratajczak, B. Machalinski, R. Mick, and A. M. Gewirtz
In Vitro and In Vivo Evidence That Ex Vivo Cytokine Priming of Donor Marrow Cells May Ameliorate Posttransplant Thrombocytopenia
Blood,
January 1, 1998;
91(1):
353 - 359.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Kouides and J. M. Bennett
Understanding the Myelodysplastic Syndromes
Oncologist,
December 1, 1997;
2(6):
389 - 401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Brown, Y. Hong, A. de Belder, H. Beacon, J. Beeso, R. Sherwood, M. Edmonds, J. F. Martin, and J. D. Erusalimsky
Megakaryocyte Ploidy and Platelet Changes in Human Diabetes and Atherosclerosis
Arterioscler. Thromb. Vasc. Biol.,
April 1, 1997;
17(4):
802 - 807.
[Abstract]
[Full Text]
|
|
|
|
|
