A phase I/II study of sequential interleukin-3 and granulocyte- macrophage
colony-stimulating factor in myelodysplastic syndromes
S Nand, J Sosman, JE Godwin and RI Fisher
Section of Hematology/Oncology, Loyola University of Chicago, Stritch
School of Medicine, Maywood, IL 60153.
In this phase I/II study, 9 patients with myelodysplastic syndromes (MDS)
were treated with interleukin-3 (IL-3) followed by granulocyte- macrophage
colony-stimulating factor (GM-CSF). Each treatment cycle was 28 days long
and administered as follows: 1 microgram/kg/d IL-3 on days 1 through 7 and
3 micrograms/kg/d GM-CSF for days 8 through 21, followed by a 7-day rest
period. IL-3 dose escalations were planned, but the dose of GM-CSF was
fixed. Three patients had refractory anemia, 4 had refractory anemia with
ringed sideroblasts, and 2 had refractory anemia with excess blasts. Six
patients were dependent on red blood cell transfusions, 1 on platelet
transfusions, and 2 on both. The absolute neutrophil count improved in 7
(77%) patients and the platelet count improved in 3 (33%) patients during
therapy. Hemoglobin levels were unchanged. A clinically relevant response
was seen in only 1 patient with thrombocytopenia, and he received five
cycles of therapy. The neutrophil count decreased in 2 patients and the
platelet count decreased in 4 patients during treatment. The toxicity of
the treatment was significant. In the first cohort of 3 patients, 1 patient
developed supraventricular tachycardia and congestive heart failure. In the
second group, 1 patient developed progressive granulocytopenia and died of
gram-negative septicemia. Because of the disparate toxicity, 3 more
patients were treated at the same dose level. One of these experienced a
high fever and bone pain requiring hospitalization. Because of these
adverse effects, the IL-3 dose was not escalated and all patients received
1 microgram/kg/d for 7 days. We believe that sequential therapy with IL-3
and GM-CSF at these dose levels causes unacceptable toxicity in patients
with MDS. The major toxic events occurred during weeks 4 and 5 after
starting treatment and may have been primarily caused by GM-CSF therapy.
Although neutrophil counts improve in most patients, the effect on red
blood cells and platelets is minimal. At present, this form of therapy
remains problematic and appears to have a limited potential in the
management of MDS.
Volume 83,
Issue 2,
pp. 357-360,
01/15/1994
Copyright © 1994 by The American Society of Hematology
