TY - JOUR
T1 - Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia
AU - Den Boer, M. L.
AU - Harms, D. O.
AU - Pieters, R.
AU - Kazemier, K. M.
AU - Göbel, U.
AU - Körholz, D.
AU - Graubner, U.
AU - Haas, R. J.
AU - Jorch, N.
AU - Spaar, H. J.
AU - Kaspers, G. J.L.
AU - Kamps, W. A.
AU - Van Der Does-Van Den Berg, A.
AU - Van Wering, E. R.
AU - Veerman, A. J.P.
AU - Janka-Schaub, G. E.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0141799965&partnerID=8YFLogxK
U2 - https://doi.org/10.1200/JCO.2003.11.031
DO - https://doi.org/10.1200/JCO.2003.11.031
M3 - Article
C2 - 12947061
SN - 0732-183X
VL - 21
SP - 3262
EP - 3268
JO - Journal of clinical oncology
JF - Journal of clinical oncology
IS - 17
ER -