PMID- 19805687
OWN - NLM
STAT- MEDLINE
DCOM- 20091117
LR  - 20220419
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 27
IP  - 31
DP  - 2009 Nov 1
TI  - Improved early event-free survival with imatinib in Philadelphia 
      chromosome-positive acute lymphoblastic leukemia: a children's oncology group 
      study.
PG  - 5175-81
LID - 10.1200/JCO.2008.21.2514 [doi]
AB  - PURPOSE: 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. PATIENTS AND 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. 
      CONCLUSION: 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.
FAU - Schultz, Kirk R
AU  - Schultz KR
AD  - 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
FAU - Bowman, W Paul
AU  - Bowman WP
FAU - Aledo, Alexander
AU  - Aledo A
FAU - Slayton, William B
AU  - Slayton WB
FAU - Sather, Harland
AU  - Sather H
FAU - Devidas, Meenakshi
AU  - Devidas M
FAU - Wang, Chenguang
AU  - Wang C
FAU - Davies, Stella M
AU  - Davies SM
FAU - Gaynon, Paul S
AU  - Gaynon PS
FAU - Trigg, Michael
AU  - Trigg M
FAU - Rutledge, Robert
AU  - Rutledge R
FAU - Burden, Laura
AU  - Burden L
FAU - Jorstad, Dean
AU  - Jorstad D
FAU - Carroll, Andrew
AU  - Carroll A
FAU - Heerema, Nyla A
AU  - Heerema NA
FAU - Winick, Naomi
AU  - Winick N
FAU - Borowitz, Michael J
AU  - Borowitz MJ
FAU - Hunger, Stephen P
AU  - Hunger SP
FAU - Carroll, William L
AU  - Carroll WL
FAU - Camitta, Bruce
AU  - Camitta B
LA  - eng
GR  - U10 CA029139/CA/NCI NIH HHS/United States
GR  - U10 CA098413/CA/NCI NIH HHS/United States
GR  - U10 CA098543/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20091005
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
SB  - IM
CIN - J Clin Oncol. 2009 Nov 1;27(31):5121-3. PMID: 19805663
MH  - Adolescent
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Benzamides
MH  - Bone Marrow Transplantation
MH  - Child
MH  - Child, Preschool
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Imatinib Mesylate
MH  - Infant
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Philadelphia Chromosome
MH  - Piperazines/*administration & dosage/adverse effects
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/genetics/mortality
MH  - Pyrimidines/*administration & dosage/adverse effects
MH  - Risk Factors
MH  - Young Adult
PMC - PMC2773475
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2009/10/07 06:00
MHDA- 2009/11/18 06:00
PMCR- 2010/11/01
CRDT- 2009/10/07 06:00
PHST- 2009/10/07 06:00 [entrez]
PHST- 2009/10/07 06:00 [pubmed]
PHST- 2009/11/18 06:00 [medline]
PHST- 2010/11/01 00:00 [pmc-release]
AID - JCO.2008.21.2514 [pii]
AID - 12514 [pii]
AID - 10.1200/JCO.2008.21.2514 [doi]
PST - ppublish
SO  - J Clin Oncol. 2009 Nov 1;27(31):5175-81. doi: 10.1200/JCO.2008.21.2514. Epub 2009 
      Oct 5.