title: Clinical significance of Philadelphia chromosome positive pediatric acute lymphoblastic leukemia in the context of contemporary intensive therapies: a report from the Children's Cancer Group.
abstract: BACKGROUND
  Children with Philadelphia (Ph) chromosome positive (+) acute lymphoblastic leukemia (ALL) represent a subgroup at very high risk for treatment failure. In this report, the authors assessed the outcome of Ph+ ALL in a large cohort of children treated on contemporary intensive chemotherapy protocols of the Children's Cancer Group (CCG).
  
  
  METHODS
  This study included 1322 children enrolled between 1988-1995 on CCG risk-adjusted studies for ALL who had centrally reviewed cytogenetic data. Thirty patients had a t(9;22)(q34;q11) translocation and were referred to as Ph+; 1292 were Ph negative(-). Outcome analyses used standard life table methods.
  
  
  RESULTS
  Compared with Ph- ALL patients, Ph+ ALL patients were more likely to be black (P=0.008), age >10 years (P=0.02), and have a leukocyte count > or =50,000/L (P <0.0001). Nearly all Ph+ (96.7%) and Ph (98.3%) patients achieved remission after induction therapy, yet event free survival outcome was significantly worse for Ph+ patients compared with Ph- patients, with 4-year estimates of 20.1% (standard deviation [SD] = 9.1%) and 75.8% (SD =1.2%), respectively (P <0.0001). This difference was maintained among patients regardless of presenting leukocyte count, age, or early response to therapy. Ten Ph+ patients underwent bone marrow transplantation (BMT) at the time of first remission; six of these patients remained event free at the time of analysis, and represent the majority (six of eight) of patients surviving event free.
  
  
  CONCLUSIONS
  The findings of the current study confirm that Ph chromosome positivity represents a significant independent adverse risk factor for childhood ALL that has not been abrogated by current intensive chemotherapy programs. BMT at the time of first remission, as well as other alternative strategies employing biotherapeutic agents, should be considered in future front-line trials for pediatric patients with Ph+ ALL.
authors.affiliation: Children's Cancer Group ALL Biology Reference Laboratory and Hughes Institute, St. Paul, Minnesota 55113, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
authors.forename: J B
authors.initials: JB
authors.lastname: Nachman
authors.forename: H N
authors.initials: HN
authors.lastname: Sather
authors.forename: M G
authors.initials: MG
authors.lastname: Sensel
authors.forename: P
authors.initials: P
authors.lastname: Kraft
authors.forename: P G
authors.initials: PG
authors.lastname: Steinherz
authors.forename: B
authors.initials: B
authors.lastname: Lange
authors.forename: R
authors.initials: R
authors.lastname: Hutchinson
authors.forename: G H
authors.initials: GH
authors.lastname: Reaman
authors.forename: P S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: N A
authors.initials: NA
authors.lastname: Heerema
mesh_terms: D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy*; D020379:Risk Adjustment; D012307:Risk Factors; D014178:Translocation, Genetic; D016896:Treatment Outcome