1. ATRA and Anthracycline based treatment in APL Ramzi Jeddi, ESH 28-30 October 2010

2. Treatment Treatment 1998-2004 1998-2004 From 2004… From 2004… APL diagnoses APL diagnoses European APL 93 Fenaux et al Fenaux et al Spanish PETHEMA LPA99 Sanz et al Sanz et al Morphology Auer rods,hypergranular,microgranular Cytogenetic analysis t(15;17) since 1997 Molecular analysis RT-PCR PML/RARA since 2004 ATRA era since 1998 Fenaux P Blood 1999;14:1192-1200 Sanz MA Blood 2004;103:1237-1243

3. European APL 93  65yr and i WBC<5 >65yr or i WBC>5 ATRA CT ATRA + CT3 ATRA + CT1 AB C CT=Ara-C+DNR

4. Patients,n34 M15 F19 Age,median,range28(6-60) WBC,median,range3(0.6-97) Morphology Hypergranular33 Variant1 Add. cytog. abn.26,4% Sanz’s score Low32% Intermediaite High 53% 15% CR82% Early death18% Results with European APL 93 (Tunis,n=24,Sfax,n=10)

5. Age,yr13252226 Sanz’s scoreHRRI HR IFCD2 - CD56 - CD2 - CD56 - NA Median,month2446364 siteMMM+CNSM Salvage therapyAPL93LPA99APL93 OutcomeDeathAliveDeath Relapse rate =14.2% ASCT PML/RARA-

7. From 2004… Spanish PETHEMA LPA 99 Spanish Contribution to APL treatment No AraC!

12. Complete remission

13. Mortality rate

14. Failure in LPA 99=Early Death HemorrhageDS

15. Hemorrhage Breccia M Haematologica 2010;853-4

16. In our study Median time from first sign and treatment 18 days (range,3-90)

17. Differentiation syndrome

18. 11 pts with DS Moderate=4 Severe=7 Mortality=3

19. BMI> 30 Baseline WBC > 20

20. BMI> 30 Baseline WBC > 20 Normal Promyelocytes APL cells OB_Rs

21. BMI> 30 Baseline WBC > 20 Normal Promyelocytes APL cells OB_Rs Adipose tissue

22. BMI> 30 Baseline WBC > 20 Normal Promyelocytes APL cells OB_Rs Adipose tissue Leptin

23. BMI> 30 Baseline WBC > 20 Normal Promyelocytes APL cells OB_Rs Adipose tissue Leptin Release of cytokines

24. BMI> 30 Baseline WBC > 20 Normal Promyelocytes APL cells OB_Rs Adipose tisuue Leptin Release of cytokines DS

25. confirmed in larger series > 1000 pts Included in APL93 & APL2000 and will be presented as poster in ASH Annual meeting 2010

26. Relapse rate

31. Childhood APL Jeddi R.Med Oncol Aug 10

32. 65 APL pts 20 Children45 Adults APL93 6 LPA99 14 LPA99 27 APL93 18 ATRA dose=25mg/m2

33. Children vs Adults

34. GIMEMA

35. Emerging problem?

36. Cumulative dose of Anthracycline - IDA =90mg/m2 - MTZ=50mg/m2

39. APL in children

40. Our series (2010) ATRA+CT 20 12(4-19) 95 75 NA 75 48 US intergroup 0129 ATRA vs No ATRA 53 ---- 81 48 -- 69 --

41. APL in children Our series (2010) ATRA+CT 20 12(4-19) 95 75 NA 75 48 US intergroup 0129 ATRA vs No ATRA 53 ---- 81 48 -- 69 --

42. APL in children Our series (2010) ATRA+CT 20 12(4-19) 95 75 NA 75 48 US intergroup 0129 ATRA vs No ATRA 53 ---- 81 48 -- 69 --

43. APL in children Our series (2010) ATRA+CT 20 12(4-19) 95 75 NA 75 48 US intergroup 0129 ATRA vs No ATRA 53 ---- 81 48 -- 69 --

44. Conclusions - Acceptable results - Improvement is required: * reach CR of 90% in adults * reach CR of 90% in adults * Maintain OS between 75-80% * Maintain OS between 75-80% - Availability of ATO for relapses

45. Aknowledgment Balkis Meddeb Hèla Ben Abid Zaher Belhadjali Raihane Ben Lakhal Hdiji Sondes Raouf Hafsia Emna Gouider Samia Ménif Lamia Aissaoui Ramzi Ben Amor Karima Kacem Walid Boutéraa Yosr Ben Abdennebi Héla Ghédira Pierre Fenaux Miguel Sanz