Indication for unrelated allo-sct in 1st CR AML

Transcription

1 Indication for unrelated allo-sct in 1st CR AML

2 It is time to say!

3 Decision of allo-sct: factors to be considered Cytogenetic risk status Molecular genetics FLT3; NPM1, CEBPA. Response to induction Refractoriness to 1st cycle of high-dose therapy Donor Looking for a suitable donor Age and Comorbidities Feasibility of allo-sct

4 Classification Characteristics Faforable CBF leukemias Intermediate-1 CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] Intermediate-2 Others Poor 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 course for achieving CR sibling HLA-matched HLAmismatched

5 EFS of the entire cohort (459 patients). Thomas X et al. Blood 2011;118: by American Society of Hematology

6 Classification Characteristics Faforable Intermediate-1 CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] Intermediate-2 Other patients Poor 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 course for achieving CR sibling HLA-matched (10/10) HLAmismatched

7 Classification Characteristics Faforable Intermediate-1 CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] Intermediate-2 45% of pts* Poor 25% of patients* Other patients 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 course for achieving CR sibling HLA-matched (10/10) HLAmismatched

8 P=.43

9 Koreth, J. et al. JAMA 2009;301: trials

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11 Classification Characteristics Faforable Intermediate-1 CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] Intermediate-2 45% of pts* Poor 25% of patients* Other patients 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 course for achieving CR sibling HLA-matched (10/10) HLAmismatched

12 Classification Faforable Intermediate-1 30% of pts* Intermediate-2 45% of pts* Poor 25% of patients* Characteristics CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] sibling HLA-matched (10/10) HLAmismatched Other patients 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 course for achieving CR * Thomas X et al. Blood 2011;118:

13 Classification Faforable Intermediate-1 30% of pts* Intermediate-2 45% of pts* Poor Characteristics CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] sibling HLA-matched (10/10) HLAmismatched Other patients 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 cycle for achieving CR * Thomas X et al. Blood 2011;118:

14 High risk was defined by: Unfavorable cytogenetic and/or No response to induction therapy

15 P=.006

16 Donor No donor

17 Classification Faforable Intermediate-1 30% of pts* Intermediate-2 45% of pts* Poor Characteristics CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] sibling HLA-matched (10/10) HLAmismatched YES YES YES Other patients 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 course for achieving CR * Thomas X et al. Blood 2011;118:

18 Classification Faforable Intermediate-1 30% of pts* Intermediate-2 45% of pts* Poor 20% of pts* Characteristics CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] sibling HLA-matched (10/10) HLAmismatched YES YES YES Other patients 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 course for achieving CR * Thomas X et al. Blood 2011;118:

19 Classification Faforable Intermediate-1 30% of pts* Characteristics CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] Intermediate-2 Other patients Poor 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 20% of pts* 2) > 1 course for achieving CR sibling HLA-matched (10/10) HLAmismatched YES YES YES

20 Classification Faforable Intermediate-1 30% of pts* Intermediate-2 Characteristics CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] sibling HLA-matched (10/10) HLAmismatched YES YES YES Other patients 50% of pts* Poor 20% of pts* 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ 2) > 1 course for achieving CR * Thomas X et al. Blood 2011;118:

21 What about patients with intermediate-risk AML in 1st CR? HLA-sibling donor YES Koreth, J. et al. JAMA 2009;301:

22 What about patients with intermediate-risk AML in 1st CR? HLA-sibling donor YES P=.01

23 What about patients with intermediate-risk AML in 1st CR? donor!

24 Limitations: * Non-randomized study * Mixture of fav/int * 39% refractory to induction (30% received 2 cycles)

25 . JCO 2006;24: Conclusion transplantation from UD led to outcomes similar to those from HLA-identical sibling donors.

26 . JCO 2006;24: Limitations: - 10/10 - Bone Marrow - Myeloablative - No ATG - Cs-A and short MTX

27 . JCO 2006;24: No conclusions can be drawn with certainty concerning allo-sct with: - HLA-mismatch - RIC - PBSC -ATG

28 Survival of patients with early, intermediate, and advanced disease depending on degree of HLA matching (8/8, 7/8, and 6/8) for HLA-A, -B, -C, and -DRB by American Society of Hematology Lee S J et al. Blood 2007;110:

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30 Is RIC a good alternative?

31 Conclusion: RIC vs MAC LFS was similar after both conditioning regimens, regardless of age.. RIC-UD extend the use of allotransplant for elderly strategies that decrease relapse should be considered mainly in younger patients.

32 Major concerns At transplant: Heterogeneous population 63% of patients were in CR 2 or more advanced disease (blasts > 5%) Cytogenetic risk status was missing in 37% of patients.

33 No firm conclusion could be drawn regarding the indication of allo-sct from UD in patients with AML in 1st CR.

34 US DATA FROM SEATTLE AND OTHER CENTERS Non myeloablative transplants in patients with AML > 50 years Boglarka Gyurkocza, Sandmaier B et al Seattle and 16 centers, JCO 2010

35 Decision of allo-sct: factors to be considered Age and Comorbidities Feasibility of allo-sct

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39 Do not put cure ahead of QOL Cure at any cost should not be a goal anymore

40 These results indicate that, compared to conventional chemotherapy, allo-cst has a significantly worse long-term impact on QOL. This needs to be considered when treatment options are discussed.

41 Classification Characteristics sibling HLA-matched (10/10) HLAmismatched Faforable Intermediate-1 CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] Intermediate-2 Other patients Poor 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ YES YES * YES YES 2) > 1 course for achieving CR * 10/10, BM, MAC, no comorbidities

42 Classification Characteristics sibling HLA-matched (10/10) HLAmismatched Faforable Intermediate-1 CBF leukemias CN-[NPM1+ or CEBPA+ w/o FLT3-ITD] Intermediate-2 Other patients Poor 1) -5, -7, 5q-, 7q-, 11q23 or MLL+ including MLL-PTD (except 9;11), t(6;9) Complex karyotype 3q26 abs or EVI-1+ YES YES * YES YES 2) > 1 course for achieving CR * 10/10, BM, MAC, no comorbidities

43 AML in 1st CR w/o sibling donor Cytogenetic & molecular risk status Fav/int-1 Int-2 Unfavorable -Age 60 -No Comorbidities -UD 10/10 -Bone Marrow - MAC allo-sct Any donor or source of SC YES YES allo-sct

44 Stop filppin through abstracts Articles must be read in deep