PHOENIXThe poor hematopoiesis that occurs in myelodysplastic
syndromes (MDS) is due to a reduced ability to respond to growth
factor stimulation. The result is that hematopoietic progenitor cells
are lost faster than blood cells can be produced.
Recombinant growth factors have not completely solved this problem,
so investigators have turned to other agents that have trophic
effects on hematopoietic progenitor cells.
Allen F. List, MD, of the University of Arizona Cancer Center,
reported at ASH that amifostine (Ethyol) can restore blood cell
counts and reduce transfusion requirements in some MDS patients.
In cell culture, amifostine promotes formation and survival of
hematopoietic progenitor cells, and previous studies have shown that
it promotes multilineage hematopoiesis in patients with MDS. Dr. List
reported on a multi-institutional phase II trial initiated as a
follow-up to those studies.
The trial enrolled adult patients with a diagnosis of primary MDS
with anemia, neutropenia, or thrombocytopenia. Patients were given
amifostine, 200 mg/m² IV three times weekly for 3 weeks followed
by 2 weeks of rest. If there was no response after a second course of
treatment, amifostine was given five times weekly.
Dr. List said that 78 patients have been enrolled, and response data
are available on 34 patients.
Amifostine treatment produced single or multilineage hematologic
improvement in 13 patients (41%). Three of 11 patients with
pretreatment neutropenia (27%) experienced an increase in absolute
neutrophil count. Five of seven patients with pretreatment
thrombocytopenia (71%) had a rise in platelets. Three patients had a
rise in reticulocyte count.
Four of 19 transfusion-dependent patients experienced a 50% or
greater decrease in red blood cell transfusion requirements. Three
patients became transfusion independent, and one has remained
transfusion independent even after cessation of amifostine.
One of seven patients receiving platelets became platelet-transfusion
independent. Improvements in bone marrow were seen in 9 of 25
evaluable patients (35%).
The criterion for myeloblastic response was a 50% or greater decrease
in the percentage of blasts for patients with 10% or more blasts at
baseline. Myeloblastic responses were seen in 6 of 31 patients (35%).
There was a correlation between pathologic response and clinical
response, Dr. List said.
The main treatment-related toxicities were fatigue (6 patients),
nausea and vomiting (5 patients), and hypotension (3 patients).
These toxicities were mild to moderate in nature with no grade
3-4 events, Dr. List said.
A Well-Tolerated Dose
The study showed the amifostine dose of 200 mg/m² three times
weekly was well tolerated. Dr. List reported that this dose produced
multilineage biologic activity, including complete remission in 35%
of patients and a reduction in bone marrow blasts in 35%.
Because of the generally good tolerance at 200 mg/m² and the
desire to determine the optimal dose with the best relative response
rate, the trial has been modified to allow a higher initial
amifostine dosage of 400 mg/m2 three times weekly.