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MFC -MRD ASSESSMENT MAY DRIVE POST INDUCTION CONSOLIDATION IN INTERMEDIATE RISK AML . IS IT TIME FOR MRD-DRIVEN DECISION MAKING?
Author(s): ,
Paola Minetto
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
,
Fabio Guolo
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
,
Daniela Guardo
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
,
Giordana Pastori
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
,
Nicoletta Colombo
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
,
Filippo Ballerini
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
,
Maurizio Miglino
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
,
Marino Clavio
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
,
Roberto Massimo Lemoli
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
Marco Gobbi
Affiliations:
Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCSS AOU San Martino-IST,Genoa,Italy
(Abstract release date: 05/19/16) EHA Library. Minetto P. 06/09/16; 132474; E925
Dr. Paola Minetto
Dr. Paola Minetto
Contributions
Abstract
Abstract: E925

Type: Eposter Presentation

Background
Since the induction therapy for acute myeloid leukemia (AML) has not changed in the last decades the optimization of post remissional therapeutic strategies is fundamental to improve patients outcome. Allogeneic  hematopoietic stem cell transplantation (BMT) offers the greatest chance of cure for most AML patients,  however in the heterogeneous group of  intermediate cytogenetic risk (int-risk) patients who achieve complete remission (CR) after induction courses, the role of BMT in 1st CR is not well defined. 

Aims
The aim of the present study was to evaluate the prognostic role of minimal residual disease (MRD) assessment through multiparameter flow cytometry  (MFC-MRD) after 1st and 2nd induction courses in int-risk patients undergoing or not BMT in 1st CR.

Methods
Fifty-five consecutive int-risk AML patients, according to MRC classification, achieving CR after induction therapy, with available post induction MFC-MRD evaluation were retrospectively included in this study. All patients were uniformly treated with a fludarabine-containing induction. Median age was 49 years. BMT in 1st CR was scheduled if an HLA identical sibling donor  or, for selected patients, if an haploidentical donor was  available. The remaining 34 patients proceeded to high dose cytarabine consolidation and  underwent BMT in 2nd CR from any donor if available (6 patients).  A positive MFC MRD was defined by the presence of no less than 25 clustered leukemic cells/105 total events  at four-color flow-cytometry. Twenty-three and 30 patients achieved MFC MRD negativity after one or two induction cycles, respectively.  Median follow up was 44 months. Relapse-free survival (RFS) was calculated from the time of diagnosis until last follow-up or documented leukemic relapse.

Results
Fifty-five consecutive int-risk AML patients, according to MRC classification, achieving CR after induction therapy, with available post induction MFC-MRD evaluation were retrospectively included in this study. All patients were uniformly treated with a fludarabine-containing induction. Median age was 49 years. BMT in 1st CR was scheduled if an HLA identical sibling donor  or, for selected patients, if an haploidentical donor was  available. The remaining 34 patients proceeded to high dose cytarabine consolidation and  underwent BMT in 2nd CR from any donor if available (6 patients).  A positive MFC MRD was defined by the presence of no less than 25 clustered leukemic cells/105 total events  at four-color flow-cytometry. Twenty-three and 30 patients achieved MFC MRD negativity after one or two induction cycles, respectively.  Median follow up was 44 months. Relapse-free survival (RFS) was calculated from the time of diagnosis until last follow-up or documented leukemic relapse.
  Num. (%)Relapse (%)median RFS3-year RFS (%)p (univ.)p (univ.)
ALL PATIENTS5516 (29)6971.4--
MFC MRD after 1st cycle negativeBMT 1st CR9/23 (39)1 (11)621000.7480.003
No BMT/2nd CR14 /23 (61)2 (14)NR83.6
MFC MRD after 1st cycle positiveBMT 1st CR12/32(38)1 (8)NR87.50.048
No BMT/2nd CR20/32 (62)12 (60)3645.2
MFC MRD after 2nd cycle negativeBMT 1st CR9/30 (30)2 (22)6287.50.7900.098
No BMT/2nd CR21/30 (70)6 (29)NR77.9
MFC MRD after 2nd cycle positiveBMT 1st CR8/19 (42)0 (0)NR1000.023
No BMT/2nd CR11/19 (58)7 (64)1533.3


Conclusion
MFC-MRD assessment after induction therapy is a strong predictor of relapse risk and could improve  risk stratification for intermediate patients. A deeper evaluation of MRD through MFC may overcome morphologic CR assessment becoming a powerful tool to delineate the therapeutic iter. Early BMT may improve the outcome of patients with persistence of MRD.

Session topic: E-poster

Keyword(s): Acute myeloid leukemia, Flow cytometry, Minimal residual disease (MRD)
Abstract: E925

Type: Eposter Presentation

Background
Since the induction therapy for acute myeloid leukemia (AML) has not changed in the last decades the optimization of post remissional therapeutic strategies is fundamental to improve patients outcome. Allogeneic  hematopoietic stem cell transplantation (BMT) offers the greatest chance of cure for most AML patients,  however in the heterogeneous group of  intermediate cytogenetic risk (int-risk) patients who achieve complete remission (CR) after induction courses, the role of BMT in 1st CR is not well defined. 

Aims
The aim of the present study was to evaluate the prognostic role of minimal residual disease (MRD) assessment through multiparameter flow cytometry  (MFC-MRD) after 1st and 2nd induction courses in int-risk patients undergoing or not BMT in 1st CR.

Methods
Fifty-five consecutive int-risk AML patients, according to MRC classification, achieving CR after induction therapy, with available post induction MFC-MRD evaluation were retrospectively included in this study. All patients were uniformly treated with a fludarabine-containing induction. Median age was 49 years. BMT in 1st CR was scheduled if an HLA identical sibling donor  or, for selected patients, if an haploidentical donor was  available. The remaining 34 patients proceeded to high dose cytarabine consolidation and  underwent BMT in 2nd CR from any donor if available (6 patients).  A positive MFC MRD was defined by the presence of no less than 25 clustered leukemic cells/105 total events  at four-color flow-cytometry. Twenty-three and 30 patients achieved MFC MRD negativity after one or two induction cycles, respectively.  Median follow up was 44 months. Relapse-free survival (RFS) was calculated from the time of diagnosis until last follow-up or documented leukemic relapse.

Results
Fifty-five consecutive int-risk AML patients, according to MRC classification, achieving CR after induction therapy, with available post induction MFC-MRD evaluation were retrospectively included in this study. All patients were uniformly treated with a fludarabine-containing induction. Median age was 49 years. BMT in 1st CR was scheduled if an HLA identical sibling donor  or, for selected patients, if an haploidentical donor was  available. The remaining 34 patients proceeded to high dose cytarabine consolidation and  underwent BMT in 2nd CR from any donor if available (6 patients).  A positive MFC MRD was defined by the presence of no less than 25 clustered leukemic cells/105 total events  at four-color flow-cytometry. Twenty-three and 30 patients achieved MFC MRD negativity after one or two induction cycles, respectively.  Median follow up was 44 months. Relapse-free survival (RFS) was calculated from the time of diagnosis until last follow-up or documented leukemic relapse.
  Num. (%)Relapse (%)median RFS3-year RFS (%)p (univ.)p (univ.)
ALL PATIENTS5516 (29)6971.4--
MFC MRD after 1st cycle negativeBMT 1st CR9/23 (39)1 (11)621000.7480.003
No BMT/2nd CR14 /23 (61)2 (14)NR83.6
MFC MRD after 1st cycle positiveBMT 1st CR12/32(38)1 (8)NR87.50.048
No BMT/2nd CR20/32 (62)12 (60)3645.2
MFC MRD after 2nd cycle negativeBMT 1st CR9/30 (30)2 (22)6287.50.7900.098
No BMT/2nd CR21/30 (70)6 (29)NR77.9
MFC MRD after 2nd cycle positiveBMT 1st CR8/19 (42)0 (0)NR1000.023
No BMT/2nd CR11/19 (58)7 (64)1533.3


Conclusion
MFC-MRD assessment after induction therapy is a strong predictor of relapse risk and could improve  risk stratification for intermediate patients. A deeper evaluation of MRD through MFC may overcome morphologic CR assessment becoming a powerful tool to delineate the therapeutic iter. Early BMT may improve the outcome of patients with persistence of MRD.

Session topic: E-poster

Keyword(s): Acute myeloid leukemia, Flow cytometry, Minimal residual disease (MRD)

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