TY - JOUR
T1 - AML/normal progenitor balance instead of total tumor load (MRD) accounts for prognostic impact of flowcytometric residual disease in AML
AU - Hanekamp, Diana
AU - Tettero, Jesse M.
AU - Ossenkoppele, Gert J.
AU - Kelder, Angèle
AU - Cloos, Jacqueline
AU - Schuurhuis, Gerrit Jan
N1 - Funding Information: This research was funded by the Netherlands Cancer Foundation/Alpe d?HuZes, project, grant number ALPE-2013-6371. Funding Information: Funding: This research was funded by the Netherlands Cancer Foundation/Alpe d’HuZes, project, grant number ALPE-2013-6371. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Measurable residual disease (MRD) in AML, assessed by multicolor flow cytometry, is an important prognostic factor. Progenitors are key populations in defining MRD, and cases of MRD involving these progenitors are calculated as percentage of WBC and referred to as white blood cell MRD (WBC-MRD). Two main compartments of WBC-MRD can be defined: (1) the AML part of the total primitive/progenitor (CD34+, CD117+, CD133+) compartment (referred to as primitive marker MRD; PM-MRD) and (2) the total progenitor compartment (% of WBC, referred to as PM%), which is the main quantitative determinant of WBC-MRD. Both are related as follows: WBC-MRD = PM-MRD × PM%. We explored the relative contribution of each parameter to the prognostic impact. In the HOVON/SAKK study H102 (300 patients), based on two objectively assessed cut-off points (2.34% and 10%), PM-MRD was found to offer an independent prognostic parameter that was able to identify three patient groups with different prognoses with larger discriminative power than WBC-MRD. In line with this, the PM% parameter itself showed no prognostic impact, implying that the prognostic impact of WBC-MRD results from the PM-MRD parameter it contains. Moreover, the presence of the PM% parameter in WBC-MRD may cause WBC-MRD false positivity and WBC-MRD false negativity. For the latter, at present, it is clinically relevant that PM-MRD ≥ 10% identifies a patient sub-group with a poor prognosis that is currently classified as good prognosis MRDnegative using the European LeukemiaNet 0.1% consensus MRD cut-off value. These observations suggest that residual disease analysis using PM-MRD should be conducted.
AB - Measurable residual disease (MRD) in AML, assessed by multicolor flow cytometry, is an important prognostic factor. Progenitors are key populations in defining MRD, and cases of MRD involving these progenitors are calculated as percentage of WBC and referred to as white blood cell MRD (WBC-MRD). Two main compartments of WBC-MRD can be defined: (1) the AML part of the total primitive/progenitor (CD34+, CD117+, CD133+) compartment (referred to as primitive marker MRD; PM-MRD) and (2) the total progenitor compartment (% of WBC, referred to as PM%), which is the main quantitative determinant of WBC-MRD. Both are related as follows: WBC-MRD = PM-MRD × PM%. We explored the relative contribution of each parameter to the prognostic impact. In the HOVON/SAKK study H102 (300 patients), based on two objectively assessed cut-off points (2.34% and 10%), PM-MRD was found to offer an independent prognostic parameter that was able to identify three patient groups with different prognoses with larger discriminative power than WBC-MRD. In line with this, the PM% parameter itself showed no prognostic impact, implying that the prognostic impact of WBC-MRD results from the PM-MRD parameter it contains. Moreover, the presence of the PM% parameter in WBC-MRD may cause WBC-MRD false positivity and WBC-MRD false negativity. For the latter, at present, it is clinically relevant that PM-MRD ≥ 10% identifies a patient sub-group with a poor prognosis that is currently classified as good prognosis MRDnegative using the European LeukemiaNet 0.1% consensus MRD cut-off value. These observations suggest that residual disease analysis using PM-MRD should be conducted.
KW - Acute myeloid leukemia
KW - MRD false negativity
KW - MRD false positivity
KW - Minimal/measurable residual disease
KW - Multiparameter flow cytometry
KW - Primitive compartment
KW - Prognostic value
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85106401565&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34073205
UR - http://www.scopus.com/inward/record.url?scp=85106401565&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers13112597
DO - https://doi.org/10.3390/cancers13112597
M3 - Article
C2 - 34073205
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 11
M1 - 2597
ER -