LEUKEMIC STEM CELL FREQUENCY COMBINED WITH MRD IS AN IMPORTANT BIOMARKER TO PREDICT RELAPSE IN ACUTE MYELOID LEUKEMIA. RESULTS FROM A PROSPECTIVE H102 STUDY
Author(s): ,
Wendelien Zeijlemaker
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
,
Rosa Meijer
Affiliations:
Clinical Trial Center-HOVON data center,Erasmus University Medical Center,Rotterdam,Netherlands
,
Angele Kelder
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
,
Jannemieke Carbaat-Ham
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
,
yvonne oussoren-brockhoff
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
,
Sander Snel
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
,
dennis veldhuizen
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
,
Willemijn Scholten
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
,
johan maertens
Affiliations:
Hematology,University Hospitals Leuven, Campus Gasthuisberg,Leuven,Belgium
,
Dimitri Breems
Affiliations:
Hematology,Ziekenhuis Netwerk Antwerpen,Antwerp,Belgium
,
Thomas Pabst
Affiliations:
Hematology,Inselspital, Bern University Hospital,Bern,Switzerland
,
Markus Manz
Affiliations:
Hematology,University Hospital Zürich,Zurich,Switzerland
,
Vincent van der Velden
Affiliations:
Immunology,Erasmus University Medical Center,Rotterdam,Netherlands
,
Jennichjen Slomp
Affiliations:
Clinical Chemistry,Medisch Spectrum Twente/Medlon,Enschede,Netherlands
,
Peter Valk
Affiliations:
Hematology,Erasmus University Medical Center,Rotterdam,Netherlands
,
Jacqueline Cloos
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
,
Bob Lowenberg
Affiliations:
Hematology,Erasmus University Medical Center,Rotterdam,Netherlands
,
gert ossenkoppele
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
Gerrit Jan Schuurhuis
Affiliations:
Hematology,VU University Medical Center,Amsterdam,Netherlands
EHA Library. Zeijlemaker W. Jun 23, 2017; 181400; S113
W Zeijlemaker
W Zeijlemaker
Contributions
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Abstract

Abstract: S113

Type: Oral Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 12:15 - 12:30

Location: Hall C

Background
Despite up-to-date risk algorithms, outcome in acute myeloid leukemia patients is still difficult to predict. Even in good risk patients relapses occur. Further refinement of currently used risk classifications is therefore warranted.

Measurable residual disease (MRD) is a well-known risk factor and the independent prognostic impact of MRD was shown for patients independent on risk groups.  Nowadays prospective studies are designed on which therapy is adapted based on MRD-positivity or negativity. Although this is a major improvement for risk stratification, relapses occur in a substantial proportion of MRD-negative patients. Previous retrospective studies have shown that the leukemic stem cell (LSC) frequency harbors important prognostic information as well (Bradbury et al, Leukemia 2015), even within MRD-negative patients (Terwijn et al. Plos one, 2013).

Aims
In this study we used data of the HOVON/SAKK H102 trial to prospectively define, using flow cytometry, the leukemic CD34+CD38- stem cell frequencies and MRD frequencies to investigate impact on patient outcome.

Methods
In 242 patients who achieved morphologic complete remission, both LSC and MRD data after two cycles of chemotherapy treatment were available. MRD-positivity was defined as a percentage of MRD-positive cells above 0.1% (as compared to total amount of WBCs) and LSC-positivity was defined as a CD34+CD38-LSC percentage above 0.0000% (LSC cut-off 0.0000%; thus no CD34+CD38-LSC events measured).

Results
Cumulative incidence of relapse (CIR) and overall survival (OS) data were investigated for four different MRD/LSC groups: 1. MRDneg + LSCneg patients (n=136) 2. MRDpos + LSCneg patients (n=28) 3. MRDneg + LSCpos patients (n=58) and 4. MRDpos + LSCpos patients (n=20). Results showed that MRDpos + LSCpos patients have the worst prognosis.

3-year CIR for the four above-defined groups was 35% (SE 4), 43% (SE 9), 53% (SE 7), and 100% (SE 0), respectively. Similar results were found for OS: 3-year OS was 66% (SE 4), 68% (SE 9), 53% (SE 8), and 100%, respectively, with 17 patients dead and 3 censored in the latter group.  When investigating the impact of MRD/LSC status in the good, intermediate, poor and very poor risk group (according to HOVON), patient numbers were sometimes small; however, results show that MRDpos + LSCpos AML patients in all different risk categories have a very poor prognosis. Moreover, multivariate analyses, containing all well known risk factors including risk group and post remission treatment, showed that MRDpos + LSCpos patients have a significantly worse cumulative incidence of relapse (hazard ratio [HR] 5.89; 95% CI 3.32-10.47) and overall survival (HR 3.62; 95% CI 1.86-7.04) as compared to the MRDneg + LSCneg patient group.

Conclusion
Overall, we conclude that our prospective results show that CD34+CD38-LSC frequency has important additional value in MRD assessment and that it especially enables to identify very poor risk patients in all different currently used risk categories. These data urge to include both MRD and LSC in future AML risk classification to better inform post-remission treatment.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Acute Myeloid Leukemia, prognosis, Minimal residual disease (MRD), Leukemic Stem Cell

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