High-dose cytarabine and daunorubicin induction and postremission
chemotherapy for the treatment of acute myelogenous leukemia in adults
GL Phillips, DE Reece, JD Shepherd, MJ Barnett, RA Brown, DA Frei-Lahr, HG Klingemann, BJ Bolwell, JJ Spinelli and RH Herzig
Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver
General Hospital, Canada.
Seventy consecutive adult patients with acute myelogenous leukemia (AML),
median age 44 years, received high-dose cytarabine (3 g/m2 every 12 hours
for 12 doses) followed by daunorubicin (45 mg/m2 daily for three doses) for
remission induction. A single, identical course was planned for
postremission therapy. Complete remission (CR) was achieved in 63 patients
(90%, 95% confidence interval [CI] 83% to 97%), 60 after a single course.
Eight patients were selected to undergo elective bone marrow
transplantation (BMT) during first CR. Of the remaining 55 patients, 40
(73%) underwent planned post-CR therapy; 15 patients did not, owing to
early relapse, excessive toxicity from the induction chemotherapy, or
refusal. Nineteen patients, including 13 who received planned post-CR
therapy, remain in continuous CR at a median follow-up of 5.2 years (range
3.0 to 7.1 years). The 5-year actuarial leukemia- free survival was 30%
(95% Cl, 19% to 42%) for all patients achieving CR and 32% (95% Cl, 19% to
47%) for the 40 patients who received the planned post-CR chemotherapy.
Analysis of various putative prognostic factors for CR and overall and
leukemia-free survival showed significance for a previous history of
myelodysplasia, higher initial leukocyte counts, certain
French-American-British (FAB) types, and certain abnormal karyotypes. None
of these factors was consistently significant regarding the above
parameters, although small patient numbers in certain analyses may have
obscured significant associations. Myelosuppression was occasionally
prolonged after remission induction and especially post-CR therapy. Severe
cerebellar toxicity was observed in 13 patients; in 11 cases, this toxicity
was fully reversible. Other serious complications were infrequent.
Intensive chemotherapy with high- dose cytarabine and daunorubicin has
substantial antileukemic activity in adult AML, and may represent an
improvement over conventional therapy. Relapses were common, however, even
in patients who received planned therapy, and substantial toxicity was
observed. The optimum use of this regimen in AML remains to be determined.
Volume 77,
Issue 7,
pp. 1429-1435,
04/01/1991
Copyright © 1991 by The American Society of Hematology
