Granulocyte-Macrophage Colony-Stimulating Factor after Initial Chemotherapy for Elderly Patients with Primary Acute Myelogenous Leukemia

doi:10.1056/NEJM199506223322503

Volume 332:1671-1677		June 22, 1995		Number 25

Granulocyte–Macrophage Colony-Stimulating Factor after Initial Chemotherapy for Elderly Patients with Primary Acute Myelogenous Leukemia

Richard M. Stone, M.D., Deborah T. Berg, R.N., Stephen L. George, Ph.D., Richard K. Dodge, M.S., Paolo Alberto Paciucci, M.D., Philip Schulman, M.D., Edward J. Lee, M.D., Joseph O. Moore, M.D., Bayard L. Powell, M.D., Charles A. Schiffer, M.D., for The Cancer and Leukemia Group B

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ABSTRACT

Background Elderly patients with primary acute myelogenous leukemia(AML) are less likely to enter remission than younger adults,in part because of a higher mortality rate related to severemyelosuppression. Granulocyte–macrophage colony-stimulatingfactor (GM-CSF) has been shown to shorten the duration of neutropeniaand decrease infectious complications when administered afterchemotherapy to patients with lymphomas and solid tumors.

Methods We randomly assigned 388 patients 60 years of age orolder who had newly diagnosed primary AML to receive placeboor GM-CSF (5 µg per kilogram of body weight per day intravenously)in a double-blind manner, beginning the day after the completionof three days of daunorubicin and seven days of cytarabine.If leukemic cells persisted in the marrow three weeks afterthe initiation of chemotherapy, further daunorubicin (two days)and cytarabine (five days) were administered. GM-CSF or placebowas given daily until the neutrophil count was at least 1000per cubic millimeter, there was evidence of the regrowth ofleukemia, or severe toxic effects attributable to the studyinfusion occurred. Patients who had a complete remission werethen randomly assigned to receive one of two intensificationregimens.

Results Of 388 patients (median age, 69 years), 193 were randomlyassigned to receive GM-CSF and 195 to receive placebo. The rateof complete remission was 51 percent (95 percent confidenceinterval, 44 to 59 percent) among those assigned to GM-CSF and54 percent (95 percent confidence interval, 47 to 61 percent)among those assigned to placebo (P = 0.61). The reasons forfailure (early death, death during marrow hypoplasia, and persistentleukemia), the incidence of severe or lethal infection, andthe incidence of the regrowth of leukemia (2 percent overall)were similar in the two groups. The median duration of neutropeniawas slightly shorter (P = 0.02) in the patients who receivedGM-CSF (15 days) than in those who received placebo (17 days),but the clinical importance of this result was minimal becausethe growth factor failed to lower the treatment-related mortalityrate or improve the rate of complete remission.

Conclusions GM-CSF, in the dose and schedule we used, does notstimulate the regrowth of leukemia, but it also does not decreasethe severe myelosuppressive consequences of initial chemotherapyor improve the response rate in patients 60 years of age orolder with primary AML. It should not be recommended for usein such patients.

Source Information

From the Division of Medical Oncology, Dana–Farber Cancer Institute, and the Department of Medicine, Harvard Medical School, Boston (R.M.S., D.T.B.); Duke University Medical Center, Durham, N.C. (S.L.G., R.K.D., J.O.M.); Mt. Sinai Medical Center, New York (P.A.P.); North Shore University Hospital, Manhasset, N.Y. (P.S.); the University of Maryland Cancer Center, Baltimore (E.J.L., C.A.S.); and Bowman Gray School of Medicine, Winston-Salem, N.C. (B.L.P.).

Address reprint requests to Dr. Stone at the Dana–Farber Cancer Institute, 44 Binney St., Boston, MA 02115.

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