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2, yeast) conferred significant benefits in terms of neutrophil recovery (≤ 500/μL: 13 versus 17 days), treatment related toxicity and grade 4/5 infectious complications. The CR rate was higher under GM-CSF (60% versus 44%) with a significant prolongation of the median survival under GM-CSF (10.6 versus 4.8 months) due to a reduction in early mortality. However, the patient number was relatively small and the follow-up was short.
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Heil G, Chadid L, Hoelzer D, Seipelt G, Mitrou P, Huber C, Kolbe K, Mertelsmann R, Lindemann A, Frisch J, et al.: GM-CSF in a double-blind randomized placebo-controlled trial in therapy of adult patients with de novo acute myeloid leukemia. Leukemia 1995, 9:3-9.
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Stone R, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman P, Lee EJ, Moore JO, Powell BL, Schiffer C: Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. N Engl J Med 1995, 332:1671-1677. Double-blind randomized, placebo-controlled trial with GM-CSF (5 μg/kg, E. coli) given after induction chemotherapy for 388 elderly (age ≥ 60 years, median = 69 years) AML patients. Although GM-CSF significantly reduced the duration of neutropenia (15 versus 17 days) it had no significant impact on the incidence of severe infections, treatment-related mortality, or CR rate thus questioning the role of GM-CSF in this situation.
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Witz F, Harrousseau JL, Sadoun A, Guyotat D, Berthou C, Cahn JY, Gardin C, Lioure B, Witz B, Desablens B, et al.: GM-CSF during and after remission induction treatment for elderly patients with acute myeloid leukemia (AML) [abstract]. Blood 1995, 86 (suppl 1):512.
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Zittoun R, Suciu S, Mandelli F, de Witte T, Thaler J, Stryckmans P, Hayat M, Peetermans M, Cadiou M, Solbu G, et al.: Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol 1996, 14:2150-2159. A randomized trial to assess the value of GM-CSF for AML induction therapy. A total of 102 patients were randomly selected to receive GM-CSF (5 μg/kg, E. coli) either concomitantly with chemotherapy (+/-), thereafter (-/+), concomitantly and therafter chemotherapy (+/+) or no GM-CSF (-/-). Priming with GM-CSF had no effect on the CR rate (72% versus 77%), whereas GM-CSF given after chemotherapy significantly decreased the CR rate in comparison with the control group (48% in the -/+ arm, 46% in the +/+ arm, versus 77% in the -/-arm). It has to be taken into consideration, however, that the remission status was assessed under GM-CSF. As a consequence, an underestimation of the CR rate due to a stimulation of early normal progenitors that could simulate the persistence or reoccurence of leukemic blasts cannot be excluded. Further randomized trials including larger series of patients are needed to settle this issue.
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