Format

Send to

Choose Destination
Leukemia. 2019 May;33(5):1102-1112. doi: 10.1038/s41375-018-0326-3. Epub 2018 Dec 12.

CD34+CD38- leukemic stem cell frequency to predict outcome in acute myeloid leukemia.

Author information

1
Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
2
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
3
Clinical trial Center- HOVON data center, Erasmus University Medical Center, Rotterdam, The Netherlands.
4
Department of Hematology, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium.
5
Department of Hematology, Ziekenhuis Netwerk Antwerpen, Antwerp, Belgium.
6
Department of Hematology, Inselspital, Bern University Hospital, Bern, Switzerland.
7
Department of Hematology, University and University Hospital Zürich, Zürich, Switzerland.
8
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
9
Department of Clinical Chemistry, Medisch Spectrum Twente/Medlon, Enschede, The Netherlands.
10
Department of Laboratory Medicine - Laboratory for Hematology, Radboud University Nijmegen Medical Center, RUNMC, Nijmegen, The Netherlands.
11
Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.
12
Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands. gj.schuurhuis@vumc.nl.

Abstract

Current risk algorithms are primarily based on pre-treatment factors and imperfectly predict outcome in acute myeloid leukemia (AML). We introduce and validate a post-treatment approach of leukemic stem cell (LSC) assessment for prediction of outcome. LSC containing CD34+CD38- fractions were measured using flow cytometry in an add-on study of the HOVON102/SAKK trial. Predefined cut-off levels were prospectively evaluated to assess CD34+CD38-LSC levels at diagnosis (n = 594), and, to identify LSClow/LSChigh (n = 302) and MRDlow/MRDhigh patients (n = 305) in bone marrow in morphological complete remission (CR). In 242 CR patients combined MRD and LSC results were available. At diagnosis the CD34+CD38- LSC frequency independently predicts overall survival (OS). After achieving CR, combining LSC and MRD showed reduced survival in MRDhigh/LSChigh patients (hazard ratio [HR] 3.62 for OS and 5.89 for cumulative incidence of relapse [CIR]) compared to MRDlow/LSChigh, MRDhigh/LSClow, and especially MRDlow/LSClow patients. Moreover, in the NPM1mutant positive sub-group, prognostic value of golden standard NPM1-MRD by qPCR can be improved by addition of flow cytometric approaches. This is the first prospective study demonstrating that LSC strongly improves prognostic impact of MRD detection, identifying a patient subgroup with an almost 100% treatment failure probability, warranting consideration of LSC measurement incorporation in future AML risk schemes.

PMID:
30542144
DOI:
10.1038/s41375-018-0326-3

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center