title: Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005.
abstract: OBJECTIVE
  In a previous analysis of 326 children with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL) treated between 1986 and 1996, hematopoietic stem-cell transplantation from HLA-matched related donors, but not from unrelated donors, offered a superior outcome than chemotherapy alone. To evaluate the impact of recent improvements in chemotherapy and transplantation, we performed a similar analysis on patients treated in the following decade.
  
  
  METHODS
  We analyzed 610 patients with Ph-positive ALL treated between 1995 and 2005 without tyrosine kinase inhibitor therapy. The median follow-up duration was 6.3 years.
  
  
  RESULTS
  Complete remission was achieved in 89% of patients. The 7-year event-free survival and overall survival rates were superior in the present cohort compared with the previous cohort (32.0% ± 2.0% v 25.0% ± 3.0, respectively, P = .007; and 44.9% ± 2.2% v 36.0% ± 3.0%, respectively, P = .017). Compared with chemotherapy alone, transplantation with matched related donors or unrelated donors in first remission (325 patients) showed an advantage with increasing follow-up, suggesting greater protection against late relapses (hazard ratio at 5 years, 0.37; P < .001). In the multivariate Cox regression analysis accounting for treatment (transplantation v no transplantation), age, leukocyte count, and early response had independent impact on treatment outcome.
  
  
  CONCLUSIONS
  Clinical outcome of children and adolescents with Ph-positive ALL has improved with advances in transplantation and chemotherapy. Transplantations with matched related donors and unrelated donors were equivalent and offered better disease control compared with chemotherapy alone. Age, leukocyte count, and early treatment response were independent prognostic indicators. The results of this study will serve as a historical reference to evaluate the therapeutic impact of tyrosine kinase inhibitors on the outcome of Ph-positive ALL.
authors.affiliation: Department of Pediatric Hematology Oncology, Azienda Ospedaliero Universitaria A. Meyer, Florence, Italy. m.arico@meyer.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.forename: Stefania
authors.initials: S
authors.lastname: Galimberti
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.forename: Vaskar
authors.initials: V
authors.lastname: Saha
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.forename: Kim
authors.initials: K
authors.lastname: Vettenranta
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006680:HLA Antigens; D047428:Protein Kinase Inhibitors