Intensification of therapy for children with lower-risk acute lymphoblastic leukemia: long-term follow-up of patients treated on Children's Cancer Group Trial 1881.
OBJECTIVE
From December 1988 through December 1992, the Children's Cancer Group (CCG) conducted a randomized trial (CCG-1881) designed to evaluate the impact of adding a single delayed intensification phase of therapy to standard therapy for patients with newly diagnosed low-risk acute lymphoblastic leukemia (ALL).


METHODS
Patients (n = 778) with newly diagnosed ALL, 2 to 9 years of age at diagnosis with an initial WBC count less than 10,000/microL, were eligible for this protocol. All patients received induction, consolidation, and interim maintenance phases of therapy over the first 16 weeks. At week 16, patients remaining in remission were randomly assigned to receive or not receive a single 7-week delayed intensification (DI) phase of therapy. Maintenance therapy was given in lieu of or after DI, with total duration of therapy approximately 3 years for boys and 2 years for girls.


RESULTS
Patients randomized to receive DI experienced fewer relapse events in all categories. Kaplan-Meier life-table estimates for continuous complete remission (CCR) at 7 years for the randomized regimens were 77% (SE, 2.4%) for the standard regimen and 83% (SE, 2.7%) for the DI regimen (P =.072). The only prognostic factor of significance post-randomization in this selected low-risk population was the day 14 marrow response (P =.0001).


CONCLUSIONS
The addition of a single DI phase of therapy was well tolerated and augmented 7-year CCR by 6% (SE of the difference, 3.3%), resulting in 26% fewer adverse events. Overall survival for eligible patients at 7 years is 90% (SE, 1.2%).
Hutchinson
Raymond J
RJ
University of Michigan Health System, Ann Arbor, MI, USA. rhutchin@umich.edu
Gaynon
Paul S
PS
Sather
Harland
H
Bertolone
Salvatore J
SJ
Cooper
Herbert A
HA
Tannous
Raymond
R
Wells
Linda M
LM
Heerema
Nyla A
NA
Sailer
Scott
S
Trigg
Michael E
ME
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D013534:Survival; D016896:Treatment Outcome