title: Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia.
abstract: OBJECTIVE
  To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol.
  
  
  METHODS
  Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol.
  
  
  RESULTS
  At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate +/- SE was 69% +/- 7.0%, 83% +/- 4.4%, and 84% +/- 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P </=.05). Resistant patients were at increased risk of an early event (nonresponse or relapse within 2.5 years of diagnosis) compared with sensitive and intermediate-sensitive patients (P =.03). The profile did not identify patients at higher risk of late relapse, which was also observed for DCLSG ALL-VII/VIII patients now analyzed at a median of 7.5 years of follow-up (range, 4.4 to 10.8 years). Despite being nondiscriminative for late relapses, the resistant profile was still the strongest prognostic factor for COALL-92 patients in a multivariate analysis including known risk factors (P =.07).
  
  
  CONCLUSIONS
  Drug resistance profiles identify patients at higher risk of early treatment failures and may, therefore, be used to improve risk-group stratification of children with ALL.
authors.affiliation: Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, PO Box 2060, 3000 CB Rotterdam, The Netherlands. m.l.denboer@erasmusmc.nl.
authors.forename: M L
authors.initials: ML
authors.lastname: Den Boer
authors.forename: D O
authors.initials: DO
authors.lastname: Harms
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: K M
authors.initials: KM
authors.lastname: Kazemier
authors.forename: U
authors.initials: U
authors.lastname: Gobel
authors.forename: D
authors.initials: D
authors.lastname: Körholz
authors.forename: U
authors.initials: U
authors.lastname: Graubner
authors.forename: R J
authors.initials: RJ
authors.lastname: Haas
authors.forename: N
authors.initials: N
authors.lastname: Jorch
authors.forename: H J
authors.initials: HJ
authors.lastname: Spaar
authors.forename: G J L
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: W A
authors.initials: WA
authors.lastname: Kamps
authors.forename: A
authors.initials: A
authors.lastname: Van der Does-Van den Berg
authors.forename: E R
authors.initials: ER
authors.lastname: Van Wering
authors.forename: A J P
authors.initials: AJ
authors.lastname: Veerman
authors.forename: G E
authors.initials: GE
authors.lastname: Janka-Schaub
mesh_terms: D000293:Adolescent; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000592:standards; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018579:Patient Selection; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000008:administration & dosage; D012306:Risk; D018709:Statistics, Nonparametric; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D011239:Prednisolone; D001215:Asparaginase