Favorable effect of priming with granulocyte colony-stimulating factor in remission induction of acute myeloid leukemia restricted to dose escalation of cytarabine

Thomas Pabst*, Edo Vellenga, Wim van Putten, Harry C. Schouten, Carlos Graux, Marie-Christiane Vekemans, Bart Biemond, Peter Sonneveld, Jakob Passweg, Leo Verdonck, Marie-Cecile Legdeur, Matthias Theobald, Emanuel Jacky, Mario Bargetzi, Johan Maertens, Gert Jan Ossenkoppele, Bob Lowenberg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)5367-5373
JournalBlood
Volume119
Issue number23
DOIs
Publication statusPublished - 7 Jun 2012

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