Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia.
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.
Den Boer
M L
ML
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.
Harms
D O
DO
Pieters
R
R
Kazemier
K M
KM
Gobel
U
U
Körholz
D
D
Graubner
U
U
Haas
R J
RJ
Jorch
N
N
Spaar
H J
HJ
Kaspers
G J L
GJ
Kamps
W A
WA
Van der Does-Van den Berg
A
A
Van Wering
E R
ER
Veerman
A J P
AJ
Janka-Schaub
G E
GE
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
D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D011239:Prednisolone; D001215:Asparaginase