TY - JOUR
T1 - Timed sequential therapy for acute myelogenous leukemia
T2 - Results of a retrospective study of 301 patients and review of the literature
AU - Norsworthy, Kelly J.
AU - DeZern, Amy E.
AU - Tsai, Hua Ling
AU - Hand, Wesley A.
AU - Varadhan, Ravi
AU - Gore, Steven D.
AU - Gojo, Ivana
AU - Pratz, Keith
AU - Carraway, Hetty E.
AU - Showel, Margaret
AU - McDevitt, Michael A.
AU - Gladstone, Douglas
AU - Ghiaur, Gabriel
AU - Prince, Gabrielle
AU - Seung, Amy H.
AU - Benani, Dina
AU - Levis, Mark J.
AU - Karp, Judith E.
AU - Smith, B. Douglas
N1 - Funding Information:
This work was supported by the National Institutes of Health Regional Oncology Research Center grant [ P30 CA006973 ].
Publisher Copyright:
© 2017
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Acute myelogenous leukemia
KW - Acute myeloid leukemia
KW - Induction chemotherapy
KW - Timed sequential therapy
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U2 - 10.1016/j.leukres.2017.08.009
DO - 10.1016/j.leukres.2017.08.009
M3 - Article
C2 - 28869816
AN - SCOPUS:85028624419
VL - 61
SP - 25
EP - 32
JO - Leukemia Research
JF - Leukemia Research
SN - 0145-2126
ER -