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Leuk Res. 2017 Oct;61:25-32. doi: 10.1016/j.leukres.2017.08.009. Epub 2017 Aug 30.

Timed sequential therapy for acute myelogenous leukemia: Results of a retrospective study of 301 patients and review of the literature.

Author information

1
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States.
2
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States; Yale Cancer Center, New Haven, CT, United States.
3
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States; Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, United States.
4
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States; Global Medicines Development, AstraZeneca, Gaithersburg, MD, United States.
5
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States; AssistRx, Orlando, FL, United States.
6
Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States. Electronic address: bdsmith@jhmi.edu.

Abstract

Timed sequential therapy (TST) aims to improve outcomes in acute myelogenous leukemia (AML) by harnessing drug-induced cell cycle kinetics of AML, where a second drug is timed to coincide with peak leukemia proliferation induced by the first drugs. We analyzed outcomes in 301 newly diagnosed AML patients treated from 2004-2013 with cytarabine, anthracycline, and etoposide TST induction. Median age was 52 (range 20-74) and complete remission rate 68%. With median follow-up 5.8 years, 5-year DFS and overall survival (OS) were 37% (95% CI 31-45%) and 32% (95% CI 27-38%), respectively. In multivariate analysis, older age, unfavorable cytogenetics, and WBC≥50×109/L resulted in worse OS. Among patients not undergoing blood and marrow transplant, a propensity score analysis, which reduces imbalance in baseline characteristics, showed consolidation with TST compared with 1 or more cycles high-dose cytarabine trended toward lower DFS and post-remission survival with hazard ratio (HR) 1.9 (95% CI 0.9-4.0), and 1.6 (95% CI 0.7-3.6), respectively. Our results demonstrate the efficacy and feasibility of TST induction for newly diagnosed patients with AML, with results comparable to that seen in clinical trials with other TST therapies and 7+3.

KEYWORDS:

Acute myelogenous leukemia; Acute myeloid leukemia; Induction chemotherapy; Timed sequential therapy

PMID:
28869816
PMCID:
PMC5813685
DOI:
10.1016/j.leukres.2017.08.009
[Indexed for MEDLINE]
Free PMC Article

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