6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.
OBJECTIVE
To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML).


METHODS
Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age > or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age > or = 60 years) x 8 instead of maintenance.


RESULTS
A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026).


CONCLUSIONS
We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.
Büchner
Thomas
T
University Medical Center, Department of Medicine, Hematology and Oncology, University of Muenster, Ulbert-Schweitzer-Str 33, D-48129 Muenster, Germany. buechnr@uni-muenster.de
Hiddemann
Wolfgang
W
Berdel
Wolfgang E
WE
Wörmann
Bernhard
B
Schoch
Claudia
C
Fonatsch
Christa
C
Löffler
Helmut
H
Haferlach
Torsten
T
Ludwig
Wolf-Dieter
WD
Maschmeyer
Georg
G
Staib
Peter
P
Aul
Carlo
C
Gruneisen
Andreas
A
Lengfelder
Eva
E
Frickhofen
Norbert
N
Kern
Wolfgang
W
Serve
Hubert L
HL
Mesters
Rolf M
RM
Sauerland
Maria Cristina
MC
Heinecke
Achim
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage
D003561:Cytarabine; D008942:Mitoxantrone; D013866:Thioguanine; D003630:Daunorubicin