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  • Title: Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia.
    Author: Den Boer ML, Harms DO, Pieters R, Kazemier KM, Gobel U, Körholz D, Graubner U, Haas RJ, Jorch N, Spaar HJ, Kaspers GJ, Kamps WA, Van der Does-Van den Berg A, Van Wering ER, Veerman AJ, Janka-Schaub GE.
    Journal: J Clin Oncol; 2003 Sep 01; 21(17):3262-8. PubMed ID: 12947061.
    Abstract:
    PURPOSE: 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. PATIENTS AND 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). CONCLUSION: 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.
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