title: The prophylactic use of granulocyte-colony stimulating factor during remission induction is associated with increased leukaemia-free survival of adults with acute lymphoblastic leukaemia: a joint analysis of five randomised trials on behalf of the EWALL.
abstract: BACKGROUND
  Granulocyte-colony stimulating factor (G-CSF) is used to prevent febrile neutropenia and support intense chemotherapy. However, its impact on long-term outcome in oncological patients including adults with acute lymphoblastic leukaemia (ALL) has not been determined so far.
  
  
  METHODS
  In the current study follow-up data from individual patients recruited in five multicentre, prospective, randomised trials were pooled to perform a joint analysis. Among 347 adults and adolescents with ALL, 185 were assigned to receive prophylactically G-CSF along with induction chemotherapy while 162 patients were treated without G-CSF support.
  
  
  RESULTS
  With the median follow-up of 5.3years, there was a tendency towards increased 5year probability of the overall survival for the G-CSF arm compared to the controls (32%±4% versus 23%±4%, p=.07), which reached statistical significance in a subgroup of T-ALL (51%±8% versus 29%±9%, p=.01) and among patients aged 21-40years (44%±6% versus 27%±6%, p=.03). The probability of leukaemia-free survival was 38%±4% and 24%±4% (p=.01) while the median remission duration equalled 33 and 17months (p=.007), respectively. In a multivariate analysis the prophylactic use of G-CSF was independently associated with reduced risk of relapse (hazard ratio (HR)=.64, p=.007) and treatment failure (HR=.67, p=.02).
  
  
  CONCLUSIONS
  The prophylactic use of G-CSF during induction of ALL is associated with improved long-term outcome and should be recommended especially in a setting of T-ALL and in 'young adults'. Our analysis provides the first direct evidence coming from prospective trials for the impact of primary G-CSF prophylaxis on disease-free survival of oncological patients.
authors.affiliation: Department of Bone Marrow Transplantation, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Helene
authors.initials: H
authors.lastname: Hallbook
authors.forename: Klaus
authors.initials: K
authors.lastname: Geissler
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Boiron
authors.forename: Francoise
authors.initials: F
authors.lastname: Huguet
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Koller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.forename: Bengt
authors.initials: B
authors.lastname: Smedmyr
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction / Q000379:methods*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor