Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia

M. L. Den Boer*, D. O. Harms, R. Pieters, K. M. Kazemier, U. Göbel, D. Körholz, U. Graubner, R. J. Haas, N. Jorch, H. J. Spaar, G. J.L. Kaspers, W. A. Kamps, A. Van Der Does-Van Den Berg, E. R. Van Wering, A. J.P. Veerman, G. E. Janka-Schaub

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)3262-3268
Number of pages7
JournalJournal of Clinical Oncology
Issue number17
Publication statusPublished - 1 Sep 2003

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