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A Placebo-Controlled Study of Recombinant Human
Granulocyte-Macrophage Colony-Stimulating Factor Administered During
and After Induction Treatment for De Novo Acute Myelogenous Leukemia in
Elderly Patients
Francis Witz,
Alain Sadoun,
Marie-Claire Perrin,
Christian Berthou,
Jean Brière,
Jean-Yves Cahn,
Bruno Lioure,
Brigitte Witz,
Sylvie François,
Bernard Desablens,
Bernard Pignon,
Pierre-Yves Le Prisé,
Bruno Audhuy,
Denis Caillot,
Philippe Casassus,
Martine Delain,
Bernard Christian,
Zéra Tellier,
Valérie Polin,
Patrick Hurteloup, and
Jean-Luc Harousseau for the Groupe Ouest Est
Leucémies Aiguës Myéloblastiques (GOELAM)
From the Clinical Hematology Units of Centre Hospitalier
Universitaire de Nancy, Nancy, France; Centre Hospitalier Universitaire
de Poitiers, Poitiers, France; Centre Hospitalier Universitaire de
Saint Etienne, Saint Etienne, France; Centre Hospitalier Universitaire
de Brest, Brest, France; Hôpital Beaujon, Clichy, France; Centre
Hospitalier Universitaire de Besançon, Besançon,
France; Centre Hospitalier Universitaire de Strasbourg,
Strasbourg, France; Centre Hospitalier Universitaire
d'Angers, Angers, France; Centre Hospitalier Universitaire d'Amiens,
Amiens, France; Centre Hospitalier Universitaire de Reims, Reims,
France; Centre Hospitalier Universitaire de Rennes, Rennes,
France; Hôpital Pasteur, Colmar, France; Centre Hospitalier
Universitaire de Dijon, Dijon, France; Hôpital Avicenne, Bobigny,
France; Centre Hospitalier Universitaire de Tours, Tours, France;
Hôpital Bon Secours, Metz, France; Pharmacia Upjohn, Guyancourt,
France; and Centre Hospitalier Universitaire de Nantes, Nantes, France.
The complete remission (CR) rate after intensive chemotherapy for
acute myelogenous leukemia (AML) remains low in elderly patients,
mainly because of a higher infectious mortality rate related to
neutropenia and an increased incidence of adverse prognostic factors.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been
shown to potentially recruit leukemic blasts into cell cycle and
improve cytotoxic effects when given during chemotherapy, and to
shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had
newly diagnosed AML were randomly assigned to receive placebo or
Escherichia coli-derived GM-CSF (5 µg/kg/d by 6-hour
intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of
neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d
on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to
7). The study drug was not administered subsequent to the induction
course. Patients who achieved a CR received continuous maintenance
therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or
not a consolidation course before maintenance therapy. The CR rate was
similar in the GM-CSF and placebo groups (63% and 60.5%,
respectively; P = .79). The mortality, rate of resistant
disease, and rate of regrowth of leukemia were also similar in both
groups. The time to neutrophil recovery was shorter in patients who
received GM-CSF (24 v 29 days; P = .0001), but the
incidence and characteristics of infectious events were not different.
The 2-year disease-free survival (DFS) rate was significantly improved
in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort
of patients aged 55 to 64, but only marginal in patients  65 years of
age. There was a trend toward a longer overall survival (OS) in the
GM-CSF group (P = .082). In summary, the administration of
GM-CSF, concomitantly with chemotherapy and thereafter during induction
course in AML, shortened the time to neutrophil recovery, but did not
improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS
were significantly prolonged in patients aged 55 to 64 treated with
GM-CSF. These results are promising and further evaluation of myeloid
growth factors in AML is warranted.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2722-2730
© 1998 by The American Society of Hematology.
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