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High-dose melphalan and granulocyte-macrophage colony-stimulating factor
for refractory multiple myeloma
B Barlogie, S Jagannath, DO Dixon, B Cheson, L Smallwood, A Hendrickson, JD Purvis, E Bonnem and R Alexanian
Division of Hematology-Oncology, University of Arkansas for Medical
Sciences, Little Rock.
High-dose melphalan has induced remissions in about 40% of patients with
refractory myeloma, but the mortality has been high, at about 20%, due to
complications of prolonged granulocytopenia. In an attempt to stimulate
earlier granulocyte recovery, recombinant human granulocyte- macrophage
colony-stimulating factor (GM-CSF) was administered subcutaneously to 23
patients with refractory myeloma who had been treated with melphalan at a
high dose of 100 mg/m2. Thirty-nine percent of patients achieved marked
tumor cytoreduction by at least 75%, 2 died within 2 months from infectious
complications during severe neutropenia; and median durations of
relapse-free and overall survival were 7 and 10+ months, respectively. The
nine patients presenting with both advanced age over 50 years and a long
history of prior therapy of over 1 year required significantly longer
median times of 31 days for granulocytes and of 63 days for platelets to
reach safe levels of at least 500/microL and 50,000/microL, respectively,
than the 14 remaining patients who had none or only one of these adverse
features (21 and 26 days, respectively). In a historic control of 43
patients treated previously with high-dose melphalan but without GM-CSF,
hematologic recovery to the aforementioned levels of granulocytes and
platelets proceeded over almost 5 weeks, regardless of age and prior
treatment exposure. Thus GM-CSF seems to hasten marrow recovery, especially
in patients with adequate normal marrow stem-cell reserve as defined by
younger age or less prior therapy. While not shortening the duration of
neutropenia, GM-CSF dose increments (from 0.25 to 0.5 to 0.75 mg/m2)
increased the incidence of severe toxicity from 0% to almost 40%,
especially among older patients. These results support the usefulness of
low-dose GM-CSF (0.25 mg/m2) in stimulating marrow recovery in selected
patients with adequate marrow reserve treated with high-dose melphalan for
refractory multiple myeloma.
Volume 76,
Issue 4,
pp. 677-680,
08/15/1990
Copyright © 1990 by The American Society of Hematology
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