title: In search of Pinkel's children: unravelling the biological heterogeneity of childhood acute lymphoblastic leukaemia by genotype and treatment molecular response.
abstract: BACKGROUND
  Acute lymphoblastic leukaemia (ALL), the commonest childhood malignancy has seen remarkable progress since the 1960s with cure rates now approaching 85%. To achieve this patients undergo intensive treatment that usually takes 2.5-3.5 years involving on average 15 different chemotherapeutic drugs. In 1971, Donald Pinkel reported Total Therapy-Protocol V that used 5 drugs and cranial radiation therapy over a similar time period. Today, one half of these patients (Pinkel's children) remain alive and free of leukaemia.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the impact post-induction minimal residual disease (MRD) levels had on survival and its relationship with the more established clinical and biological prognostic predictors of outcome in the hope of identifying a subgroup of patients that are at very low risk of failure.
  
  
  METHODS
  A retrospective review of 250 Irish children with ALL was carried out. MRD status after 28 days of induction chemotherapy and other known predictors of outcome were correlated with 5 year event-free survival (EFS).
  
  
  RESULTS
  MRD status was the strongest predictor of outcome with 5 year EFS rates greater that 90% seen in those patients with low-risk MRD and this was associated with TEL/AML1 rearrangement, high hyperdiploidy (HH) karyotype and female gender.
  
  
  CONCLUSIONS
  Both MRD and karyotype are powerful determinants of outcome in childhood ALL. Therefore, it is reasonable to conclude that the majority of children cured by Pinkel et al. in the late 1960s were most likely composed of low-risk MRD, TEL/AML1 and HH patients.
authors.affiliation: Department of Haematology, Our Lady's Children's Hospital, Crumlin, Dublin, 12, Ireland. jkrawczyk@pro.onet.pl
authors.forename: J
authors.initials: J
authors.lastname: Krawczyk
authors.forename: S
authors.initials: S
authors.lastname: Maguire
authors.forename: N
authors.initials: N
authors.lastname: Sandys
authors.forename: J
authors.initials: J
authors.lastname: Kelly
authors.forename: C
authors.initials: C
authors.lastname: Ryan
authors.forename: A
authors.initials: A
authors.lastname: O'Marcaigh
authors.forename: L
authors.initials: L
authors.lastname: Storey
authors.forename: S
authors.initials: S
authors.lastname: Rooney
authors.forename: C
authors.initials: C
authors.lastname: Phillips
authors.forename: O P
authors.initials: OP
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D049673:History, 20th Century; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D008297:Male; D018365:Neoplasm, Residual / Q000453:epidemiology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics* / Q000266:history; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein