Inhibitors of histon deacetylase (HDAC) and DNA methyltransferase in treatment children with acute myeloid leukemia, effectiveness and place

The results of treatment children with acute myeloid leukemia (AML) are not satisfied yet. The standard chemotherapy allows achieve complete remission in 92–96 % of patients, but disease free survival (DFS) and event free survival (EFS) are not good yet.
In a new study – NII DOG AML 2012 – the specific aim was to explore effectiveness demethylating drug (Decitabine) and inhibitors of histon deacetylase (HDAC) to find the place in standard chemotherapy.
From 01.2013 to 09.2016 26 patients were enrolled into NII DOG AML 2012 study. The average was 6.5 ± 1.24 years (6 mo – 16 years): 15 males and 11 females, standard (SR) – 2 (7.7 %), intermediate (IR) – 7 (26.9 %) and high (HR) – 17 (65.4 %) risk groups.
Chemotherapy consisted on 5 courses for HR and IR (AIE, HAM, AI, hAM, HAE) and 4 courses for SR (AIE, HAM, hAM, HAE). Epigenetic therapy consisted of Valproic acid (VA) weeks 1–78, All Trans Retinoic Acid (ATRA) 1–43 days and from the day one to day 14 of the every course chemotherapy and Decitabine in “window” regime before induction (5 pts) and on day 16 after beginning of induction.
Decitabine was given as a demethylating drug 20 mg/m2 for 5 days in “window” regime before induction (AIE). There were no any toxicity and we did not check decrease of blasts in BM and peripheral blood after Decitobine, one of them developed relapse and one died from severe infection, 3 pts are alive, but two of them underwent haploidentical HSCT. Decitobine was moved on the day 16. Now, 21 pts got this therapy, all of them achieved CR after AIE with VA, ATRA and Decitobine, two pts did not respond to induction and achieved CR just after Decitobine. Three years DFS and EFS were the same – 67.9 ± 12 % with median follow up 28.1 ± 3.1 mo, OS – 81.6 ± 9.6 % with median follow up 31.0 ± 2.6 mo. None of the patients underwent HSCT.
Thus, epigenetic therapy increases rate of CR, DFS and EFS in children with AML. Demethylating drug has to be used during aplasia and HDAC inhibitors – during the whole chemotherapy program.

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