Response assessment in acute myeloid leukemia by flow cytometry supersedes cytomorphology at time of aplasia, amends cases without molecular residual disease marker and serves as an independent prognostic marker at time of aplasia and post-induction

Köhnke, Thomas; Bücklein, Veit; Rechkemmer, Sandra; Schneider, Stephanie; Rothenberg‐Thurley, Maja; Metzeler, Klaus H.; Sauerland, Maria-Cristina; Hiddemann, Wolfgang; Spiekermann, Karsten; Subklewe, Marion

doi:10.3324/haematol.2018.215236

Cited by 3 publications

(3 citation statements)

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“…To validate the proposed MRD approach, the results were compared with two already published and established methods to analyze MFC data for presence of MRD: a traditional (manual) flow cytometry approach based on the conventional detection of an aberrant LAIP (convLAIP) [ 19 , 38 ] and an unsupervised computational approach (Unsup) [ 39 , 40 ]. The convLAIP approach was restricted to the samples used to calculate the IRR of the proposed approach ( n = 117, see below).…”

Section: Methodsmentioning

confidence: 99%

“…In the LAIP concept, one or more individual LAIP are identified at diagnosis and tracked during follow-up. Depending on the antibody panel, at least one LAIP with aberrant antigen expression pattern is found in 80–95% of patients at diagnosis [ 18 , 19 ]. The DfN strategy searches for aberrant immunophenotypes rarely observed in leukemia-free BM during follow up independent of pre-treatment samples [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Reproducible measurable residual disease detection by multiparametric flow cytometry in acute myeloid leukemia

et al. 2022

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Measurable residual disease (MRD) detected by multiparametric flow cytometry (MFC) is associated with unfavorable outcome in patients with AML. A simple, broadly applicable eight-color panel was implemented and analyzed utilizing a hierarchical gating strategy with fixed gates to develop a clear-cut LAIP-based DfN approach. In total, 32 subpopulations with aberrant phenotypes with/without expression of markers of immaturity were monitored in 246 AML patients after completion of induction chemotherapy. Reference values were established utilizing 90 leukemia-free controls. Overall, 73% of patients achieved a response by cytomorphology. In responders, the overall survival was shorter for MRDpos patients (HR 3.8, p = 0.006). Overall survival of MRDneg non-responders was comparable to MRDneg responders. The inter-rater-reliability for MRD detection was high with a Krippendorffs α of 0.860. The mean time requirement for MRD analyses at follow-up was very short with 04:31 minutes. The proposed one-tube MFC approach for detection of MRD allows a high level of standardization leading to a promising inter-observer-reliability with a fast turnover. MRD defined by this strategy provides relevant prognostic information and establishes aberrancies outside of cell populations with markers of immaturity as an independent risk feature. Our results imply that this strategy may provide the base for multicentric immunophenotypic MRD assessment.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reproducible measurable residual disease detection by multiparametric flow cytometry in acute myeloid leukemia

et al. 2022

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“…Currently, various techniques, including multiparameter flow cytometry and molecular assays, are used for MRD assessment. 9,10 Molecular MRD measurements based on quantitative PCR (qPCR) are potentially more sensitive than multiparameter flow cytometry but are dependent on the presence of suitable target lesions, such as core binding factor fusion transcripts or mutated NPM1. 11 Absolute quantification of MRD levels by qPCR requires the use of external reference standards.…”

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confidence: 99%