Clinical and cytogenetic responses to granulocyte-macrophage colony-
stimulating factor in therapy-related myelodysplasia
WJ Gradishar, MM Le Beau, R O'Laughlin, JW Vardiman and RA Larson
Department of Medicine, University of Chicago, Pritzker School of Medicine,
IL.
We treated 10 patients with a therapy-related myelodysplastic syndrome with
escalating doses of granulocyte-macrophage colony-stimulating factor
(GM-CSF; sargramostim) in a phase II trial and used sequential cytogenetic
analyses to determine whether there was stimulation of nonclonal
hematopoiesis. The GM-CSF was administered by continuous intravenous
infusion over 2 hours daily for 14 days, followed by a 14- day rest period.
The initial starting dose was 60 micrograms/m2/d. The GM-CSF dose was
escalated within individual patients to 125 micrograms/m2, 250
micrograms/m2, and then 500 micrograms/m2/d until the peripheral blood
neutrophil count at least doubled and exceeded 1,000/microL. GM-CSF
treatment then continued in monthly maintenance cycles. During 57 treatment
courses, the neutrophil count increased in 52 but only doubled and exceeded
1,000/microL in 21. Mild eosinophilia was stimulated in five patients, but
only two had greater than 1,000 eosinophils/microL. In only three patients
was any stimulation of platelet or red blood cell production observed, and
thus, little change in transfusion requirements occurred. The bone marrow
karyotypes from individual patients either remained completely abnormal or
became increasingly abnormal over the course of treatment. We found no
evidence that GM-CSF preferentially stimulated normal marrow stem cells to
proliferate or had the ability to eradicate the cytogenetically abnormal
clone by inducing terminal differentiation. Although the effect on
granulopoiesis was transient and dependent on continued GM- CSF treatment,
the increase in the neutrophil count was clinically important in some
patients, allowing more effective control of ongoing infections.
Volume 80,
Issue 10,
pp. 2463-2470,
11/15/1992
Copyright © 1992 by The American Society of Hematology
