{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:36:24Z","timestamp":1786977384041,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Valproic acid (VPA) inhibits histone deacetylase activity and, synergizing with all\u2010trans retinoic acid (ATRA), achieves differentiation induction of myeloid blast cells in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We used VPA in 58 patients with acute myeloid leukemia (AML) who were too old and\/or medically unfit to receive intensive chemotherapy (32 AML secondary to myelodysplastic syndrome [MDS], 22 de novo AML, 4 AML secondary to myeloproliferative syndrome). VPA serum concentrations were 50\u2013100 \u03bcg\/mL. Thirty\u2010one patients received VPA monotherapy. ATRA was added later in 13 patients who did not respond or who relapsed. Another 27 patients received VPA plus ATRA from the start. Median treatment duration was 93 days for VPA and 88 days for ATRA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The response rate was only 5% according to International Working Group (IWG) criteria for AML but was 16% when IWG response criteria for MDS were used, which capture hematologic improvement and stabilization of the disease. These endpoints, which are not necessarily correlated with diminishing blast counts, are relevant for the patients' quality of life. Among 23 patients with a peripheral blast count &gt; 5%, 6 (26%) showed a diminishing blast count, and 5 of these had a complete peripheral blast clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Future trials should combine VPA with chemotherapy or demethylating agents. Cancer 2006. \u00a9 2005 American Cancer Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.21552","type":"journal-article","created":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T17:25:58Z","timestamp":1133457958000},"page":"112-119","source":"Crossref","is-referenced-by-count":180,"title":["The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all\u2010trans retinoic acid in patients with acute myeloid 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