Details

Autor(en) / Beteiligte

• Tassara, Michela
• Döhner, Konstanze
• Brossart, Peter
• Held, Gerhard
• Götze, Katharina
• Horst, Heinz-A.
• Ringhoffer, Mark
• Köhne, Claus-Henning
• Kremers, Stephan
• Raghavachar, Aruna
• Wulf, Gerald
• Kirchen, Heinz
• Nachbaur, David
• Derigs, Hans Günter
• Wattad, Mohammed
• Koller, Elisabeth
• Brugger, Wolfram
• Matzdorff, Axel
• Greil, Richard
• Heil, Gerhard
• Paschka, Peter
• Gaidzik, Verena I.
• Göttlicher, Martin
• Döhner, Hartmut
• Schlenk, Richard F.

Titel

Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients

Ist Teil von

• Blood, 2014-06, Vol.123 (26), p.4027-4036

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• The outcome of patients with acute myeloid leukemia who are older than 60 years has remained poor because of unfavorable disease characteristics and patient-related factors. The randomized German-Austrian AML Study Group 06-04 protocol was designed on the basis of in vitro synergistic effects of valproic acid (VPA) and all-trans retinoic acid with chemotherapy. Between 2004 and 2006, 186 patients were randomly assigned to receive 2 induction cycles with idarubicin, cytarabine, and all-trans retinoic acid either with VPA or without (STANDARD). In all patients, consolidation therapy was intended. Complete remission rates after induction tended to be lower in VPA compared with STANDARD (40% vs 52%; P = .14) as a result of a higher early death rate (26% vs 14%; P = .06). The main toxicities attributed to VPA were delayed hematologic recovery and grade 3/4 infections, observed predominantly during the second induction cycle. After restricting VPA to the first induction cycle and reducing the dose of idarubicin, these toxicities dropped to rates observed in STANDARD. After a median follow-up time of 84 months, event-free and overall survival were not different between the 2 groups (P = .95 and P = .57, respectively). However, relapse-free-survival was significantly superior in VPA compared with STANDARD (24.4% vs 6.4% at 5 years; P = .02). Explorative subset analyses revealed that AML with mutated Nucleophosmin 1 (NPM1) may particularly benefit from VPA. This trial was registered at www.clinicaltrials.gov as #NCT00151255. •The addition of valproic acid to intensive induction therapy in combination with all-trans retinoic acid did not result in an improvement of clinical outcome.•Valproic acid-related hematologic toxicity and higher death rates were observed when valproic acid and idarubicin were given in parallel.