Long-term results following treatment of newly-diagnosed acute myelogenous leukemia with continuous-infusion high-dose cytosine arabinoside
Ghaddar, H.M.; Plunkett, W.; Kantarjian, H.M.; Pierce, S.; Freireich, E.J.; Keating, M.J.; Estey, E.H.
Leukemia 8(8): 1269-1274
1994
ISSN/ISBN: 0887-6924 PMID: 8057660 Document Number: 438901
The long-term results in 130 patients with newly diagnosed acute myelogenous leukemia treated with continuous infusion high-dose ara-C (1.5 gm/m-2/day x 4 days, CIHDAC) were compared with those in 264 patients treated in previous studies with standard dose ara-C (70-90 mg/m-2/d x 7 days) plus either adriamycin (Ad-OAP), or amsacrine (AMSA-OAP). All patients have been followed at least 5 years. Patients in first CR at 5 years (FCR-5) treated on protocols prior to CIHDAC had only 5% chance of relapse (median subsequent follow-up of 9 years). Therefore, we considered patients in FCR-5 potentially cured. The two groups were similar with respect to known prognostic factors and CR rates. Although remission duration and survival were shorter with CIHDAC than Ad-OAP/AMSA-OAP, the percent of patients potentially cured was similar (10 vs. 15%). Marked differences between regimens were seen in inv(16) and t(15;17) patients. CIHDAC was better for patients with inv(16) with more patients in FCR-5 (80 vs. 38%), longer remission duration and survival, and lower incidence of CNS relapse (0 vs. 43%). The Ad-OAP/AMSA-OAP protocols were superior in patients with t(15;17). We also measured steady-state ara-CTP concentrations (ara-CTP-ss) in 54 CIHDAC-treated patients presenting with high-blast count. While there was no correlation between ara-CTP-ss and response duration, all five patients in FCR-5 in whom ara-CTP-ss was measured had high concentrations. These data support the concept that patients with AML should be treated differently according to cytogenetics. Inv(16) patients should be treated with high-dose ara-C while t(15;17) should rely more on anthracycline exposure.