title: Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine.
abstract: The clinical value of chemotherapy sensitization of acute myeloid leukemia (AML) with G-CSF priming has remained controversial. Cytarabine is a key constituent of remission induction chemotherapy. The effect of G-CSF priming has not been investigated in relationship with variable dose levels of cytarabine. We randomized 917 AML patients to receive G-CSF (456 patients) or no G-CSF (461 patients) at the days of chemotherapy. In the initial part of the study, 406 patients were also randomized between 2 cytarabine regimens comparing conventional-dose (199 patients) versus escalated-dose (207 patients) cytarabine in cycles 1 and 2. We found that patients after induction chemotherapy plus G-CSF had similar overall survival (43% vs 40%, P = .88), event-free survival (37% vs 31%, P = .29), and relapse rates (34% vs 36%, P = .77) at 5 years as those not receiving G-CSF. However, patients treated with the escalated-dose cytarabine regimen benefited from G-CSF priming, with improved event-free survival (P = .01) and overall survival (P = .003), compared with patients without G-CSF undergoing escalated-dose cytarabine treatment. A significant survival advantage of sensitizing AML for chemotherapy with G-CSF was not apparent in the entire study group, but it was seen in patients treated with escalated-dose cytarabine during remission induction. The HOVON-42 study is registered under The Netherlands Trial Registry (www.trialregister.nl) as #NTR230.
authors.affiliation: Department of Medical Oncology, University Hospital, Bern, Switzerland. thomas.pabst@insel.ch
authors.forename: Thomas
authors.initials: T
authors.lastname: Pabst
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Wim
authors.initials: W
authors.lastname: van Putten
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.forename: Carlos
authors.initials: C
authors.lastname: Graux
authors.forename: Marie-Christiane
authors.initials: MC
authors.lastname: Vekemans
authors.forename: Bart
authors.initials: B
authors.lastname: Biemond
authors.forename: Peter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Jakob
authors.initials: J
authors.lastname: Passweg
authors.forename: Leo
authors.initials: L
authors.lastname: Verdonck
authors.forename: Marie-Cecile
authors.initials: MC
authors.lastname: Legdeur
authors.forename: Matthias
authors.initials: M
authors.lastname: Theobald
authors.forename: Emanuel
authors.initials: E
authors.lastname: Jacky
authors.forename: Mario
authors.initials: M
authors.lastname: Bargetzi
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
mesh_terms: D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor