Abstract
In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.
Highlights
Treatment outcomes for acute myeloid leukemia (AML) have been less favorable than expected despite recent advances in understanding underlying disease biology. Except for those with acute promyelocytic leukemia (APL), a disease that had its natural history rewritten after the advent of all-trans-retinoic acid [1,2], the survival rates of patients with AML are still low [3,4]
We retrospectively evaluated a cohort of adults with nonpromyelocytic leukemia who were treated in a single center to identify variables that could have affected the outcomes, including the role of three distinct doses of cytarabine administered in the consolidation phase
It has recently been suggested that the induction doses should be increased, even in older patients, in order to promote complete remission (CR) and overall survival [24]
Summary
Treatment outcomes for acute myeloid leukemia (AML) have been less favorable than expected despite recent advances in understanding underlying disease biology. Except for those with acute promyelocytic leukemia (APL), a disease that had its natural history rewritten after the advent of all-trans-retinoic acid [1,2], the survival rates of patients with AML are still low [3,4]. Described as a successful treatment for AML with a favorable karyotype [9,10], the high-dose cytarabine consolidation regime has proven to be a key influence on overall survival, disease-free survival, and event-free survival rates [11,12] It is still not clear which patients truly benefit from intensive cytarabine consolidation and what is the best dose and regimen [13,14,15]. We retrospectively evaluated a cohort of adults with nonpromyelocytic leukemia who were treated in a single center to identify variables that could have affected the outcomes, including the role of three distinct doses of cytarabine administered in the consolidation phase
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