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Fredly, H. et al.

Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or 6-mercaptopurin can be safe and effective in patients with advanced acute myeloid leukaemia--a report of five cases.

Disease-stabilizing therapy with the histone deacetylase inhibitor valproic acid and all-trans retinoic acid (ATRA) has been investigated in acute myelogenous leukemia (AML) in a number of trials. Experimental studies suggest that valproic acid induces a broad chemoresistant phenotype in human AML cells; however, clinical observations combining valproic acid with conventional therapy in a disease-stabilizing setting have not been reported that would confirm this as a clinical issue. We describe five patients receiving oral treatment with low-dose oral 6-mercaptopurin and/or hydroxyurea together with ATRA+valproric acid+theophylline. Hyperleukocytosis was controlled by low doses of the cytotoxic drugs, no unexpected toxicity appeared and the increases in normal peripheral blood cell counts induced by ATRA+valproic acid+theophylline were maintained during therapy. In two patients increasing blast counts later occurred during chemotherapy; a change to the alternative cytotoxic drug was then effective in controlling hyperleukocytosis. We conclude that valproic acid+ATRA+theophylline combined with 6-mercaptopurin or hydroxyurea can be safe and effective in palliative treatment of human AML.[1]

References

Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or 6-mercaptopurin can be safe and effective in patients with advanced acute myeloid leukaemia--a report of five cases. Fredly, H., Stapnes Bjørnsen, C., Gjertsen, B.T., Bruserud, Ø. Hematology (2010) [Pubmed]

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