Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study.
OBJECTIVE
Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups.


METHODS
We evaluated whether imatinib (340 mg/m(2)/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT.


RESULTS
Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% +/- 11% (95% CI, 64% to 90%), more than twice historical controls (35% +/- 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% +/- 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% +/- 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction.


CONCLUSIONS
Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.
Schultz
Kirk R
KR
Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, University of British Columbia, B.C.'s Children's Hospital, Vancouver, BC, V6H 3V4, Canada. kschultz@interchange.ubc.ca
Bowman
W Paul
WP
Aledo
Alexander
A
Slayton
William B
WB
Sather
Harland
H
Devidas
Meenakshi
M
Wang
Chenguang
C
Davies
Stella M
SM
Gaynon
Paul S
PS
Trigg
Michael
M
Rutledge
Robert
R
Burden
Laura
L
Jorstad
Dean
D
Carroll
Andrew
A
Heerema
Nyla A
NA
Winick
Naomi
N
Borowitz
Michael J
MJ
Hunger
Stephen P
SP
Carroll
William L
WL
Camitta
Bruce
B
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D055815:Young Adult
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate