Haematologica, Vol 92, Issue 8, 1119-1122 doi:10.3324/haematol.11262
Copyright © 2007 by Ferrata Storti Foundation
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Myelodysplastic Syndromes

Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes

Timo Siitonen, Timo Timonen, Eeva Juvonen, Venla Terävä, Anu Kutila, Tuomo Honkanen, Maija Mikkola, Heikki Hallman, Marjut Kauppila, Pirkko Nyländen, Eira Poikonen, Auvo Rauhala, Marjatta Sinisalo, Merja Suominen, Eeva-Riitta Savolainen, Pirjo Koistinen Finnish Leukemia Group

From the Departments of Internal Medicine Oulu University Hospital (TS, TT, PK); Helsinki University Central Hospital (EJ); Turku University Central Hospital (MK); Tampere University Hospital (MS); Keski-Pohjanmaa Central Hospital (VT); Mikkeli Central Hospital (AK, MM); Päijät-Häme Central Hospital (TH); Keski-Suomi Central Hospital (HH); Länsi-Pohja Central Hospital (PN); Peijas Hospital (EP); Vaasa Central Hospital (AR); Kanta-Häme Central Hospital (MS); Department of Clinical Chemistry, Oulu University Hospital, Finland (E-RS)

Correspondence: Timo Siitonen, M.D., Ph.D., Department of Internal Medicine, Oulu University Hospital, PL 20, OYS 90029, Finland. E-mail: timo.siitonen{at}ppshp.fi

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.

Key words: valproic acid, 13-cis retinoic acid, myelodysplastic syndromes.