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A two-step timed sequential treatment for acute myelocytic leukemia
RB Geller, PJ Burke, JE Karp, RL Humphrey, HG Braine, RW Tucker, MG Fox, M Zahurak, L Morrell and KL Hall
Adult Leukemia Program, Johns Hopkins Oncology Center, Baltimore.
Since 1980, adults with acute myelocytic leukemia (AML) have been treated
on two clinical studies using intensive timed sequential therapy. All
patients ages 16 to 80, including those with secondary AML (SAML) and those
with AML preceded by a hematologic disorder (AHD), were treated, regardless
of medical complications at the time of diagnosis. The first study combined
high doses of cytarabine (ara-C, AC) and daunorubicin (DRN, D) in sequence
(Ac2-D-Ac) and resulted in a complete remission rate of 55%. A group of
these patients selected by functional status was able to receive a second
course of therapy in remission, which resulted in a disease-free survival
(DFS) of greater than 40% at 7 years. Because of toxicity in that study,
114 patients were entered on a second trial initiated 4 years ago, using a
less aggressive first course, with amsacrine, to achieve a stable remission
(Ac2-D-Amsa). This first treatment was followed by a more intensive second
course (Ac6-D-Ac). With this two-step approach, a higher complete remission
(CR) rate (76% for de novo AML and 54% for SAML-AHD) was achieved, and more
patients were able to receive the second course of therapy. At the current
median follow-up of 26 months, the median duration of DFS and overall
survival are 11 and 14 months for patients with de novo AML. Age less than
or equal to 55 is the most significant prognostic factor for both prolonged
DFS and overall survival, with median durations of 17 and 18 months,
respectively, for these younger patients. Patients with SAML-AHD remain
relatively refractory to treatment despite aggressive chemotherapy, with
median durations of DFS and overall survival of 9 months and 5 months,
respectively.
Volume 74,
Issue 5,
pp. 1499-1506,
10/01/1989
Copyright © 1989 by The American Society of Hematology
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