PMID- 21172891
OWN - NLM
STAT- MEDLINE
DCOM- 20110310
LR  - 20220224
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 29
IP  - 4
DP  - 2011 Feb 1
TI  - Identification of patients with acute myeloblastic leukemia who benefit from the 
      addition of gemtuzumab ozogamicin: results of the MRC AML15 trial.
PG  - 369-77
LID - 10.1200/JCO.2010.31.4310 [doi]
AB  - PURPOSE: Antibody-directed chemotherapy for acute myeloid leukemia (AML) may 
      permit more treatment to be administered without escalating toxicity. Gemtuzumab 
      ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is 
      internalized when binding to the epitope. We previously established that it is 
      feasible to combine GO with conventional chemotherapy. We now report a large 
      randomized trial testing the addition of GO to induction and/or consolidation 
      chemotherapy in untreated younger patients. PATIENTS AND METHODS: In this 
      open-label trial, 1,113 patients, predominantly younger than age 60 years, were 
      randomly assigned to receive a single dose of GO (3 mg/m(2)) on day 1 of 
      induction course 1 with one of the following three induction schedules: 
      daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or 
      fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin. 
      In remission, 948 patients were randomly assigned to GO in course 3 in 
      combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine. 
      The primary end points were response rate and survival. RESULTS: The addition of 
      GO was well tolerated with no significant increase in toxicity. There was no 
      overall difference in response or survival in either induction of consolidation. 
      However, a predefined analysis by cytogenetics showed highly significant 
      interaction with induction GO (P = .001), with significant survival benefit for 
      patients with favorable cytogenetics, no benefit for patients with poor-risk 
      disease, and a trend for benefit in intermediate-risk patients. An internally 
      validated prognostic index identified approximately 70% of patients with a 
      predicted benefit of 10% in 5-year survival. CONCLUSION: A substantial proportion 
      of younger patients with AML have improved survival with the addition of GO to 
      induction chemotherapy with little additional toxicity.
FAU - Burnett, Alan K
AU  - Burnett AK
AD  - Department of Haematology, Cardiff University School of Medicine, Heath Park, 
      Cardiff, United Kingdom. BurnettAK@cardiff.ac.uk
FAU - Hills, Robert K
AU  - Hills RK
FAU - Milligan, Donald
AU  - Milligan D
FAU - Kjeldsen, Lars
AU  - Kjeldsen L
FAU - Kell, Jonathan
AU  - Kell J
FAU - Russell, Nigel H
AU  - Russell NH
FAU - Yin, John A L
AU  - Yin JA
FAU - Hunter, Ann
AU  - Hunter A
FAU - Goldstone, Anthony H
AU  - Goldstone AH
FAU - Wheatley, Keith
AU  - Wheatley K
LA  - eng
GR  - G9901427/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20101220
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 (Aminoglycosides)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 93NS566KF7 (Gemtuzumab)
SB  - IM
CIN - J Clin Oncol. 2011 Feb 1;29(4):349-51. PMID: 21172885
MH  - Adolescent
MH  - Adult
MH  - Aminoglycosides/administration & dosage
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Cytogenetic Analysis
MH  - Denmark
MH  - Female
MH  - Gemtuzumab
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Kaplan-Meier Estimate
MH  - Leukemia, Myeloid, Acute/*drug therapy/genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - New Zealand
MH  - Odds Ratio
MH  - *Patient Selection
MH  - Precision Medicine
MH  - Proportional Hazards Models
MH  - Risk Assessment
MH  - Risk Factors
MH  - Survival Rate
MH  - Time Factors
MH  - Treatment Outcome
MH  - United Kingdom
MH  - Young Adult
EDAT- 2010/12/22 06:00
MHDA- 2011/03/11 06:00
CRDT- 2010/12/22 06:00
PHST- 2010/12/22 06:00 [entrez]
PHST- 2010/12/22 06:00 [pubmed]
PHST- 2011/03/11 06:00 [medline]
AID - JCO.2010.31.4310 [pii]
AID - 10.1200/JCO.2010.31.4310 [doi]
PST - ppublish
SO  - J Clin Oncol. 2011 Feb 1;29(4):369-77. doi: 10.1200/JCO.2010.31.4310. Epub 2010 
      Dec 20.