title: Prospective randomized trial to evaluate two delayed granulocyte colony stimulating factor administration schedules after high-dose cytarabine therapy in adult patients with acute lymphoblastic leukemia.
abstract: In acute lymphoblastic leukemia (ALL), treatment with granulocyte colony stimulating factor (G-CSF) during remission induction shortens granulocytopenia and may decrease morbidity due to infections. However, the optimal timing of G-CSF administration after chemotherapy is not known. In a prospective randomized multi-center study, adult ALL patients were treated with high-dose ARA-C [HDAC, 3 g/m(2) bid (1 g/m(2) bid for T-ALL) days 1-4] and mitoxantrone (MI 10 mg/m(2) days 3-5). They were randomized to receive recombinant human G-CSF (Lenograstim) 263 micro g/day SC starting either from day 12 (Group 1) or day 17 (Group 2). Fifty-five patients (41 male, 14 female) with a median age of 34 years (range: 18-55 years) were enrolled into the study; 50 patients were evaluable. The median duration of neutropenia <500/ micro l after HDAC/MI was 12 days (range: 7-22 days) in the early G-CSF Group 1 and also 12 days (range: 4-22 days) in the late G-CSF Group 2; this was shorter than in the historical control group (15 days, range: 4-43 days, n=46) where the patients received identical cytotoxic treatment without G-CSF. Seventeen infections were observed in 14 patients in Group 1 (47%) and 13 infections in 10 patients in Group 2 (50%) compared to 27 infections in 49 patients of the historical control (54%). In Group 1, the patients received a median of 11 injections with G-CSF (range: 7-22) compared to 7 injections (range: 4-19) in Group 2. The total administered dose of G-CSF in Group 2 was significantly reduced by 40% ( P<0.0001). The delayed start of G-CSF after HDAC/MI in ALL achieves the same clinical benefit compared to the earlier initiation of G-CSF. The reduction of treatment costs by reducing the total G-CSF dose may be important in future treatment with this hematopoietic growth factor.
authors.affiliation: Department of Hematology and Oncology, Johann Wolfgang Goethe University Hospital, Theodor-Stern-Kai 7, 60596 Frankfurt/Main, Germany. W.K.Hofmann@em.uni-frankfurt.de
authors.forename: W K
authors.initials: WK
authors.lastname: Hofmann
authors.forename: G
authors.initials: G
authors.lastname: Seipelt
authors.forename: S
authors.initials: S
authors.lastname: Langenhan
authors.forename: R
authors.initials: R
authors.lastname: Reutzel
authors.forename: D
authors.initials: D
authors.lastname: Schott
authors.forename: O
authors.initials: O
authors.lastname: Schoeffski
authors.forename: H J
authors.initials: HJ
authors.lastname: Illiger
authors.forename: F
authors.initials: F
authors.lastname: Hartmann
authors.forename: L
authors.initials: L
authors.lastname: Balleisen
authors.forename: A
authors.initials: A
authors.lastname: Franke
authors.forename: F
authors.initials: F
authors.lastname: Fiedler
authors.forename: C
authors.initials: C
authors.lastname: Huber
authors.forename: H
authors.initials: H
authors.lastname: Rasche
authors.forename: L
authors.initials: L
authors.lastname: Bergmann
authors.forename: A
authors.initials: A
authors.lastname: Ganser
authors.forename: C
authors.initials: C
authors.lastname: Pott
authors.forename: R
authors.initials: R
authors.lastname: Pasold
authors.forename: C
authors.initials: C
authors.lastname: Rudolph
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: N
authors.initials: N
authors.lastname: Gökbuget
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000191:economics; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000517:prevention & control; D009894:Opportunistic Infections / Q000517:prevention & control; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000191:economics; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor