title: Hematologic improvement and response in elderly AML/RAEB patients treated with valproic acid and low-dose Ara-C.
abstract: The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has been shown to be active on acute myeloid leukemia (AML) and refractory anemia with excess of blasts (RAEB). Thirty-one elderly AML/RAEB patients (AML n=25; RAEB n=6) with a high rate of comorbidity were entered in a phase II study with low-dose cytarabine (Ara-C) and VPA. Fitness was evaluated by means of the Comprehensive Geriatric Assessment (CGA), including the Cumulative Illness Rating Scale (CIRS) score, the self-sufficiency scores of Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL). Eight patients obtained a lasting complete remission and 3 other patients obtained hematologic improvement for a total response rate of 35%. Five of 11 responding patients were relapsed or resistant after a previous treatment with Ara-C. Seven of 11 responding patients were assessed as frail at enrollment and/or had IADL impairment. Grades 3 and 4 toxicities were mainly hematological. Low-dose Ara-C and VPA is a relatively non-toxic combination with good therapeutic activity in elderly patients with AML/RAEB. This therapeutic approach represents an alternative treatment for patients who cannot undergo standard induction therapy.
authors.affiliation: Division of Hematology, Azienda Ospedaliera SS Arrigo e Biagio e Cesare Arrigo, Alessandria, Italy. mcorsetti@ospedale.al.it
authors.forename: M T
authors.initials: MT
authors.lastname: Corsetti
authors.forename: F
authors.initials: F
authors.lastname: Salvi
authors.forename: S
authors.initials: S
authors.lastname: Perticone
authors.forename: A
authors.initials: A
authors.lastname: Baraldi
authors.forename: L
authors.initials: L
authors.lastname: De Paoli
authors.forename: S
authors.initials: S
authors.lastname: Gatto
authors.forename: D
authors.initials: D
authors.lastname: Pietrasanta
authors.forename: M
authors.initials: M
authors.lastname: Pini
authors.forename: V
authors.initials: V
authors.lastname: Primon
authors.forename: F
authors.initials: F
authors.lastname: Zallio
authors.forename: A
authors.initials: A
authors.lastname: Tonso
authors.forename: M G
authors.initials: MG
authors.lastname: Alvaro
authors.forename: G
authors.initials: G
authors.lastname: Ciravegna
authors.forename: A
authors.initials: A
authors.lastname: Levis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000927:Anticonvulsants / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D014635:Valproic Acid