title: Impact of age, leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era: results of the FRALLE 93 study.
abstract: BACKGROUND
  We explored the heterogeneity of philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL) in a study of the effect of early features on prognosis in children. Here we report the long-term results of the FRALLE 93 study conducted in the era before the use of tyrosine kinase inhibitors.
  
  
  METHODS
  Between 1993 and 1999, 36 children with Ph1-ALL were enrolled into the FRALLE 93 protocol. After conventional four-drug induction, children were stratified by availability of an HLA-matched sibling.
  
  
  RESULTS
  Complete remission (CR) was observed in 26 children (72%), of which 13 underwent allogeneic bone marrow transplantation (BMT). Thirty-one children were good responders to prednisone, defined on day 8, and 21 were good responders to chemotherapy, defined by day-21 bone marrow (M1). Overall five-year disease-free survival (DFS) was 42 +/- 9.7%. Based on multivariate analysis, two groups showed marked differences in five-year outcome: children with age<10, leukocyte count <100,000/mm3 and day-21 M1 marrow had a more favorable prognosis (14 pts: 100% CR, event free survival [EFS]: 57%, overall survival [OS]: 79%), than the high-risk group (22 patients: 55% CR, EFS: 18%, OS: 27%) (p < 0.005). We also observed a non statistically significant difference (p = 0.14) in outcome between these groups for transplanted patients (5-year DFS: 83 +/- 14% and 33 +/- 15%, respectively).
  
  
  CONCLUSIONS
  Age, leukocyte count and early response to treatment defined by the D21 bone marrow response provide an accurate model for outcome prediction. The combination of available tools such as minimal residual disease assessment with determination of these simple factors could be useful for refining indications for BMT in the current era of tyrosine-kinase inhibitor-based therapy.
authors.affiliation: Department of Pediatric Hematology, University Hospital of Rennes, Rennes, France. virginie.gandemer@chu-rennes.fr
authors.forename: Virginie
authors.initials: V
authors.lastname: Gandemer
authors.forename: Marie-Francoise
authors.initials: MF
authors.lastname: Auclerc
authors.forename: Yves
authors.initials: Y
authors.lastname: Perel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vannier
authors.forename: Edouard
authors.initials: E
authors.lastname: Le Gall
authors.forename: Francois
authors.initials: F
authors.lastname: Demeocq
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Christophe
authors.initials: C
authors.lastname: Piguet
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stephan
authors.forename: Odile
authors.initials: O
authors.lastname: Lejars
authors.forename: Marianne
authors.initials: M
authors.lastname: Debre
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Guy
authors.initials: G
authors.lastname: Leverger
authors.forename: Andre
authors.initials: A
authors.lastname: Baruchel
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000367:Age Factors; D018943:Anthracyclines; D000971:Antineoplastic Combined Chemotherapy Protocols; D001215:Asparaginase; D001549:Benzamides; D001853:Bone Marrow / Q000187:drug effects*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003348:Cortisone; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D011241:Prednisone / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage*; D012008:Recurrence; D016896:Treatment Outcome; D014750:Vincristine; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014750:Vincristine; D000068877:Imatinib Mesylate; D001215:Asparaginase; D003348:Cortisone; D011241:Prednisone