Hematologic improvement and response in elderly AML/RAEB patients treated with valproic acid and low-dose Ara-C
Introduction
Therapy for AML patients who cannot undergo standard induction protocols because of age, comorbidity or clinical condition has for years been limited to support and cytoreduction [1]. For these patients, a new strategy includes molecules with differentiating or proapoptotic activity [2], [3], [4]. These molecules could achieve therapeutic effect without inducing aplasia. Histone deacetylase inhibitors (HDCAi) have been shown to modulate gene expression with pro-differentiative effects [5], [6]. In this category, valproic acid (VPA) is a short-chain fatty acid with HDCAi activity. This drug has been shown to overcome the differentiation block in AML blasts [7]. VPA can be used orally and has a low toxicity profile. We aimed to assess the therapeutic activity and feasibility of use of VPA in combination with low-dose Ara-C in elderly and frail AML/RAEB patients.
Section snippets
Study group eligibility
Written informed consent was obtained before therapy. Diagnosis of AML and RAEB was defined according to the French–American–British (FAB) classification and WHO recommendation [8], [9]. IPSS scores were calculated for each RAEB patient [10]. Specific criteria for enrolment in the study were absence of indications for standard chemotherapy due to: (1) AML patients being considered unfit for aggressive chemotherapy for documented comorbidity and/or age over 65 years; (2) primary refractory or
Patients
Between November 2005 and May 2008, 31 patients with advanced AML/RAEB were enrolled. Patient's characteristics are listed in Table 1. Median age was 72 years (range of 55–84 years). Twenty-five patients had AML; in this group 14 patients had diagnosis of de novo AML, 6 patients had AML with dysplasia, 3 patients had AML progression from MDS, 2 patients had AML transformation from essential thrombocythemia and chronic myelomonocytic leukemia. Six patients had RAEB-2. In 2 of these, the disease
Discussion
The treatment outcome for elderly patients with AML/RAEB is unsatisfactory and has not substantially improved over recent years [1], [16], [17]. These patients are excluded from clinical trials because they are considered not fit enough, although there is no general consensus on determining which patients over the age of 65 are good candidates for intensive therapy. These patients may benefit from treatments with new drugs with differentiating activity more than conventional cytotoxic therapies
Conflict of interest statement
None declared.
Acknowledgements
This work was partially supported by fund from AIL (Associazione Italiana Ricerca sul Cancro).
Author's contributions: MTC, FS, AB, LDP, SG, DP, MP, VP, FZ, AT, MGA, GC served as investigators on this trial, enrolling patients and contributed to data interpretation, reviewed and provided their comments on this manuscript. AL did the initial conception and design of the study. MTC drafted the final manuscript. SP served as the trial statistician.
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