Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial.
OBJECTIVE
To optimize treatment for younger patients with acute myeloid leukemia and high-risk myelodysplastic syndrome by comparing induction options and the number of consolidation courses and whether consolidation should include transplantation.


METHODS
We randomly assigned 1,658 patients younger than age 60 years to receive mitoxantrone/cytarabine/etoposide versus cytarabine/daunorubicin/etoposide and subsequently 1,193 patients to daunorubicin/cytarabine/thioguanine (DAT) where the cytarabine dose was standard (S-DAT) versus double the standard dose (H-DAT). Patients in this randomization were randomly assigned to all-trans-retinoic acid or not. In consolidation, 992 patients were randomly assigned between a total of four courses versus five courses, and 324 patients who were not good risk were randomly assigned to transplantation or chemotherapy as the final course.


RESULTS
Complete remission (CR) was achieved in 74% of patients and CR without recovery was achieved in an additional 11%; overall survival (OS) at 8 years was 38%. No differences in CR, relapse-free survival, relapse, or OS were seen between any of the induction randomizations except for a reduction in relapse risk (RR) on the mitoxantrone arm, which was offset by increased myelosuppression and deaths in CR. The addition of a fifth course did not improve OS and may be detrimental in older patients. Although transplantation reduced RR, it did not improve OS for the intermediate-risk group but was probably of benefit in high-risk patients.


CONCLUSIONS
Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.
Burnett
Alan K
AK
Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom. BurnettAK@Cardiff.ac.uk
Hills
Robert K
RK
Milligan
Donald W
DW
Goldstone
Anthony H
AH
Prentice
Archibald G
AG
McMullin
Mary-Frances
MF
Duncombe
Andrew
A
Gibson
Brenda
B
Wheatley
Keith
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage; D055815:Young Adult
D003561:Cytarabine; D014212:Tretinoin; D005047:Etoposide; D008942:Mitoxantrone; D013866:Thioguanine; D003630:Daunorubicin