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Epigenetic Therapy for Treatment of Pediatric Acute Myeloid Leukemia

Epigenetic Therapy for Treatment of Pediatric Acute Myeloid Leukemia. Oncology Hospitals. Moscow Balashiha Krasnodar Rostov-on-Don Ekaterinburg Sankt-Petersburg Archangelsk Voronezh Protocol AML-2002: from 07/ 2002 to 09/ 2006 Protocol AML-2007: from 10/2006 to 02/2012

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Epigenetic Therapy for Treatment of Pediatric Acute Myeloid Leukemia

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  1. Epigenetic Therapy for Treatment of Pediatric Acute Myeloid Leukemia

  2. Oncology Hospitals • Moscow • Balashiha • Krasnodar • Rostov-on-Don • Ekaterinburg • Sankt-Petersburg • Archangelsk • Voronezh Protocol AML-2002: from 07/2002 to 09/2006 Protocol AML-2007: from 10/2006 to 02/2012 Results on 10/31/2013

  3. Diagnosis Marrow, blood and cerebrospinal fluid is examined 1. Cytomorphology, 2. Flow cytometry, 3. Tested for chromosomal abnormalitis by cytogenetics • AML-2002, N=51 (42,1%) • AML-2007, N=70 (57,9%)

  4. Patient Characteristics

  5. Cytogenetic Characteristics (р=0,2)

  6. Risk Groups

  7. Frequency Risk Groups Patients Enrolled onAML-2002 and AML-2007

  8. Response to Induction Therapy Response on the 15 day: • Good Response (М-1) – bone marrow < 5% blasts,peripheral blood 0% blasts • Partial Response (М-2) – bone marrow 6 - 25% blasts , peripheral blood 0% blasts • Non Response (М-3) – bone marrow > 25% blasts Response after induction therapy: • Complete remission - Bone marrow: < 5% blasts - Peripheral blood: Neutrophils > 1,0 ×109/L, Platelets > 100×109/L, Hgb> 10 g/dL - Non extra medullar tumor • No remission - Bone marrow: > 6-25% blasts - Refractory AML - Bone marrow: >25% blasts

  9. Response in 15 Day AML-2002 AML -2007 Р=0,14

  10. Frequency Response in 15 day in Terms of Risk Groups

  11. Response After Induction Therapy р=0,1 AML-2002 AML-2007

  12. Statute After Induction Therapy

  13. Disease-Free Survival

  14. Event-Free Survival

  15. Overall Survival

  16. Disease-Free Survival (Standard risk)

  17. Overall Survival (Standard risk)

  18. Disease-Free Survival (Intermediate risk)

  19. Overall Survival (Intermediate risk)

  20. Disease-Free Survival (High risk)

  21. Overall Survival (High risk)

  22. Disease-Free Survival (Unfavourable risk)

  23. Overall Survival (Unfavourable risk)

  24. Five-year DFS • Five-year OS

  25. High-dose of chemotherapy &AutologousSctAML-2002 • 2 patients of Standard risk group (after Induction therapy more 5% blasts in bone marrow) • 10 patients of Intermediate risk group (25 patients needed) • 2 patients of High risk group (13 patients needed)

  26. Disease-Free Survival (AML-2002 Protocol)

  27. Overall Survival (AML-2002 Protocol)

  28. Toxicity • All-trans-retinoic acid (ATRA) • Side effects – headachein12 children (17,1%) – «ATRA syndrome» waspresentinremissioninductionperiodinonlyonepatient Valproicacid • Side effects – Myelosuppression no different average duration ofneutropenia 21,3±3,7 daysafterAML-2002 22,1±4,2 daysafterAML-2007

  29. Conclusions 1.The number of remissions inpatients, whoweretreatedafterAML-2007protocolwashigher. The number ofcomplete remissions hasrisenaccuratelyas a resultofinductiontherapyinchildrenwith a highriskof AML, thatreceivedtreatmentafterAML-2007 includingepigenetictherapy. 2. Thankstoputtingonepigenetic drugsimprovedvaluesofDFS, EFSand OSwerereachedinchildrenwith AML. 3. DFShasbeenincreasedaccuratelyinthecombinationofepigeneticandchemotherapyinpatientswithhighorunfavorableriskof AML. 4. The survival values grew up more and accurately in children under one year old. 5. Epigeneticdrugs didnotincreasetoxicitywhilebeingaddedtothechemotherapy.

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