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IN ACUTE MYELOID LEUKEMIA, THE USE IN INDUCTION OF STANDARD DOSE ARA-C IS ASSOCIATED WITH A BETTER QUALITY OF RESPONSE AS COMPARED TO AN INDUCTION REGIMEN.

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Presentation on theme: "IN ACUTE MYELOID LEUKEMIA, THE USE IN INDUCTION OF STANDARD DOSE ARA-C IS ASSOCIATED WITH A BETTER QUALITY OF RESPONSE AS COMPARED TO AN INDUCTION REGIMEN."— Presentation transcript:

1 IN ACUTE MYELOID LEUKEMIA, THE USE IN INDUCTION OF STANDARD DOSE ARA-C IS ASSOCIATED WITH A BETTER QUALITY OF RESPONSE AS COMPARED TO AN INDUCTION REGIMEN CONTAINING HIGH DOSE ARA-C

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3 HIGH DOSE ARA-C (HDAC) IN INDUCTION THERAPY Parameter ALSG SWOGAMLCG Median age of patients (range), years 41 (15–60)‏ND (15–64)‏44 (16–60)‏ De novo AML/secondary AML Yes/noYes/yesYes/no No. of induction therapy courses 112 Ara-C dose (mg/m 2 per day)‏ Standard arm Experimental arm 100 x x x x x x 3 Combination partners during induction therapy Standard arm Experimental arm DNR, VP16 DNR DNR, 6-TG MTZ Uniform therapy in complete remission YESNOYES Kern and Estey, Cancer 2006 Tabella 1

4 1)No increase in the CR rate in patients less than 60 years of age 2)In ALSG and SWOG experience improvement in DFS and OS was observed in patients ≤ 50 years 3)increased toxicity: CNS, infections Kern and Estey, Cancer 2006 Buchner T et al, JCO 2009 HDAC IN INDUCTION THERAPY

5 EORTC/GIMEMA AML-12: 1)Significantly higher CR rate than SD- Ara-C 2)No improvement in DFS (median FUP 3 years)‏ 3)Similar toxicity profile Willemze, ASH 2008 [134]

6 HDAC IN INDUCTION THERAPY AGE LESS 60 YEARS Guidelines SDACHDAC SIEGrade AGrade B NCCN Category 1 Category 2B British SocietyGrade A

7 AIMS To explore the impact on the “quality of response” of an induction regimen containing standard dose (SD) ARA-C versus HDAC by measuring minimal residual disease (MRD) once CR was achieved.

8 Design of MRD studies in AML by Flow Multiple staining at diagnosis Identification of “leukemia-associated” phenotype Definition of a patient’s “immunologic fingerprint” Immunologic fingerprint used during follow-up Venditti et al, Blood 2000 Buccisano et al, Leukemia 2006 Maurillo et al, JCO 2008

9 EORTC/GIMEMA AML-10 protocol Induction Consolidation autoBMTautoPSCT R EORTC/GIMEMA AML-12 protocol Induction Consolidation R autoPSCT IL-2no IL-2 AlloSCT HLA sibling donor available Very high-risk Tabella 2

10 EORTC/GIMEMA AML-10 protocol Induction Anthracycline ® ARA-C 100 mg/m2 day 1-10 etoposide 50 mg/m2 day 1-5 Consolidation (Arm A)‏ ARA-C 500 mg/m2/q12 hrs day 1-6 daunorubicin 50 mg/m2, day 4-6 ®= A) DNR 50 mg/m 2 B) MTZ 12 mg/m 2 C) IDA 10 mg/m 2 EORTC/GIMEMA AML-12 protocol Induction DNR 50 mg/m 2 ARA-C ® etoposide 50 mg/m2 day 1-5 Consolidation ARA-C 500 mg/m2/q12 hrs day 1-6 daunorubicin 50 mg/m2, day 4-6 ®= A) ARA-C 100 mg/m2 day 1-10 B) 3000 mg/m2/q12 hrs on days 1,3,5,7 Tabella 3

11 CHARACTERISTIC ARA-C DOSE N° 110 (%) Tabella 4

12 CHARACTERISTIC ARA-C DOSE N° 110 (%) Tabella 5

13 Maurillo et al, JCO 2008 An MRD level of 3.5×10 -4 cells or higher at the end of consolidation significantly predicts relapse and survival Figura1

14 POST INDUCTION SDACHDAC p = % (46/74)‏ 38% (28/74)‏ 17% (6/36)‏ 83% (30/36)‏ Figura 2

15 POST CONSOLIDATION SDACHDAC p = % (43/74)‏ 42% (31/74)‏ 17% (6/35)‏ 83% (29/35)‏ Figura 3

16 Figura 4

17 Figura5

18 DFS AND OS ACCORDING TO ARA-C DOSE Figura 6

19 DFS ACCORDING TO ARA-C DOSE AND MRD STATUS AFTER CONSOLIDATION Figura 7

20 OS ACCORDING TO ARA-C DOSE AND MRD STATUS AFTER CONSOLIDATION Figura 8

21 CONCLUSIONS Previous studies have shown that MRD assessment impacts independently on the prognosis of AML and proves useful to modulate the intensity of post-remission therapy Achievement of MRD negative status after front-line induction-consolidation therapy is essential for AML outcome Induction regimen containing SDAC given for 10 days results in a more efficient clearance of leukemic burden and a “better” quality of response compared to a similar regimen HDAC based


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