title: Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes.
abstract: Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.
authors.affiliation: Department of Internal Medicine, Oulu University Hospital, OYS, Finland. timo.siitonen@ppshp.fi
authors.forename: Timo
authors.initials: T
authors.lastname: Siitonen
authors.forename: Timo
authors.initials: T
authors.lastname: Timonen
authors.forename: Eeva
authors.initials: E
authors.lastname: Juvonen
authors.forename: Venla
authors.initials: V
authors.lastname: Terävä
authors.forename: Anu
authors.initials: A
authors.lastname: Kutila
authors.forename: Tuomo
authors.initials: T
authors.lastname: Honkanen
authors.forename: Maija
authors.initials: M
authors.lastname: Mikkola
authors.forename: Heikki
authors.initials: H
authors.lastname: Hallman
authors.forename: Marjut
authors.initials: M
authors.lastname: Kauppila
authors.forename: Pirkko
authors.initials: P
authors.lastname: Nyländen
authors.forename: Eira
authors.initials: E
authors.lastname: Poikonen
authors.forename: Auvo
authors.initials: A
authors.lastname: Rauhala
authors.forename: Marjatta
authors.initials: M
authors.lastname: Sinisalo
authors.forename: Merja
authors.initials: M
authors.lastname: Suominen
authors.forename: Eeva-Riitta
authors.initials: ER
authors.lastname: Savolainen
authors.forename: Pirjo
authors.initials: P
authors.lastname: Koistinen
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000368:Aged; D000369:Aged, 80 and over; D002117:Calcitriol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002613:Cheilitis / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000139:chemically induced; D006657:Histones / Q000378:metabolism; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011014:Pneumonia / Q000139:chemically induced; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D006657:Histones; D014635:Valproic Acid; D015474:Isotretinoin; D002117:Calcitriol