Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia.
OBJECTIVE
Intensification by high-dose cytarabine in postremission or induction therapy and prolonged maintenance are established strategies to improve the outcome in patients with acute myeloid leukemia (AML). Whether additional intensification can add to this effect has not yet been determined.


METHODS
A total of 1,770 patients (age 16 to 85 years) with de novo or secondary AML or high-risk myelodysplastic syndrome (MDS) were randomly assigned upfront for induction therapy containing one course with standard dose and one course with high-dose cytarabine, or two courses with high-dose cytarabine, and in the same step received postremission prolonged maintenance or busulfan/cyclophosphamide chemotherapy with autologous stem-cell transplantation.


RESULTS
The complete remission rate in patients younger than 60 and > or = 60 years of age was 70% and 53%, respectively. The overall survival at 3 years in the two age groups was 42% and 19%, the relapse-free survival was 40% and 19%, and the ongoing remission duration was 48% and 22%, respectively. There were no significant differences in these results between the two randomized induction arms or between the two postremission therapy arms. There was no significant difference in any prognostic subgroup according to secondary AML/MDS, cytogenetics, WBC, lactate dehydrogenase, and early blast clearance.


CONCLUSIONS
The regimen of one course with standard-dose cytarabine and one course with high-dose cytarabine for induction, and prolonged maintenance for postremission chemotherapy in patients with AML is not improved by additional escalation in cytotoxic treatment.
Büchner
Thomas
T
Department of Medicine, Hematology/Oncology,University of Muenster, Muenster, Germany. buechnr@uni-muenster.de
Berdel
Wolfgang E
WE
Schoch
Claudia
C
Haferlach
Torsten
T
Serve
Hubert L
HL
Kienast
Joachim
J
Schnittger
Susanne
S
Kern
Wolfgang
W
Tchinda
Joelle
J
Reichle
Albrecht
A
Lengfelder
Eva
E
Staib
Peter
P
Ludwig
Wolf-Dieter
WD
Aul
Carlo
C
Eimermacher
Hartmut
H
Balleisen
Leopold
L
Sauerland
Maria-Cristina
MC
Heinecke
Achim
A
Wörmann
Bernhard
B
Hiddemann
Wolfgang
W
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery*; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D012307:Risk Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D003561:Cytarabine; D008942:Mitoxantrone; D007770:L-Lactate Dehydrogenase