Epigenetic therapy in childhood AML (pilot study)
Alexander V. Popa1, Elena S. Gorohova2, Elena V. Flejshman3, Larisa G. Fechina4, Vladimir V. Lebedev5, Karapet S. Aslanyan6, Evgenia V. Inyushkina2, Svetlana A. Mayakova1, Irina E. Gavrilova1, Olga P. Chlebnikova4, Elmira G. Boichenko7, George L. Mentkevich1
1RAMS N.N. Blokhin RCRC, Pediatric Oncology and Hematology Research Institute, Hematology/Oncology Department, Russia; 2Moscow Region Oncology Hospital, Pediatric Oncology Department, Russia; 3RAMS N.N. Blokhin RCRC, Institute of Cancer Genesis, Laboratory of Cytogenetic, Russia; 4Ekaterinburg Region Pediatric Cancer Research Center, Russia; 5Krasnodar Region Pediatric Hospital, Hematology Department, Russia; 6Rostov-na-Donu Region Pediatric Hospital, Hematology/Oncology Department, Russia;
7St. Petersburg Children’s Hospital N1, Russia
We presume that a combination of CT and epigenetic therapy (ET) might improve the results in pediatric AML.Methods: Between October 2006 and August 2008, 42 children with AML were enrolled in the study: 25 boys (59.5%) and 17 girls (40.5%); the mean age was 8.3±0.8 ys. Seven pts (16.7%) were found to be standard risk (SR), 15 (34.7%) intermediate risk (IR), and 20 (48.6%) high risk (HR). Standard cytogenetics was performed in 32 patients.
Treatment was carried out according to the NII-DOG-AML 2007 protocol. CT for SR consisted of induction (AIE), consolidation (Ara-C 75mg/m2/d 4 days N4 every week, daunomycin 30mg/m2/m N4 every week, and 6–MP 60mg/m2/d days 1–28), and two courses HAE. For pts with IR and HR, CT had 4 courses: AIE, HAM in timing as induction, and postinduction (FLAG, HAE). ET consisted of ATRA 25mg/m2/d+valproic acid (VPA) 25mg/kg/d. Children with SR got VPA during maintenance until the seventy-eighth week and ATRA for 14 days every 14 days. Pts with IR and HR got VPA during all treatment for 18 mo and ATRA during the first 45 days and for 14 days with every consecutive CT course.
Response was assessed on day 15. CR (M-1) was observed in all 7 SR pts, in 14 IR pts (93.3%), and in 14 HR pts (70%); PR (M-2) was observed in 1 IR pt (6.7%). All 4 children who did not respond on day 15 were in HR. After induction, CR was seen in 39 pts (92.9%). CR was not observed in 3 pts: 1 died from invasive aspergillosis, and 2 never got into CR. The 29 mo EFS was 57.2±8.3%, median follow up 18.8±1.8 mo, DFS 67.7±8.3%, and median follow up 21.1±1.8 mo. ET did not lead to any severe complications.
Chemotherapy combined with epigenetic treatment lead to complete remission in 39 out of 42 pts with AML without any extra toxicity. These results allow us to go on with this study.
childhood acute myeloid leukemia, chemotherapy, epigenetic therapy