Treatment of High-Risk Relapsing or Refractory AML with M-AMSA and ID-ARAC

Abstract

The prognosis of patients with refractory or relapsing acute myeloid leukemia (AML) is poor. Easy to handle treatment regimens with high effectivity and tolerable toxicity are warranted. High-dose cytosine arabinoside (HD ara-C) is effective in relapsing or resistant AML [1–9]. However, doses of 3000 mg/m2 ara-C are associated with significant mucositis, cutaneous, liver, and CNS toxicity. Pharmacological data indicate that intermediate doses of ara-C may be as effective as high doses [10]. The therapeutic effect of HD ara-C can be enhanced substantially by combination with anthracyclines [6, 11–17] but this may involve the risk of cumulative cardiotoxicity in heavily pretreated and elderly patients. The antineoplastic, DNA-topoisomerase II-reactive DNA intercalating acridine derivative 4′(9-acridinylamino) methanesulfon-m-anisidine (m-AMSA) is active in AML [18–25]. M-AMSA may be combined with ara-C without a significant negative effect on ara-CTP accumulation, elimination, or total intracellular exposure with ara-CTP [26]. As a single agent m-AMSA is as effective as HD ara-C [3]. In combination with conventional ara-C it is at least as effective as daunorubicin [27, 28]. Against this background we have studied a condensed 5-day combination of m-AMSA and intermediate-dose ara-C (ID ara-C) in a population of patients with high-risk AML.KeywordsAcute Myeloid LeukemiaAcute LeukemiaCytosine ArabinosideHannover Medical SchoolRelapse Acute Myeloid LeukemiaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.