ELN iMDS flow working group validation of the monocyte assay for chronic myelomonocytic leukemia diagnosis by flow cytometry

Orianne Wagner-Ballon*, Peter Bettelheim, Jeroen Lauf, Frauke Bellos, Matteo Della Porta, Erica Travaglino, Dolores Subira, Irene Nuevo Lopez, Sihem Tarfi, Theresia M. Westers, Ulrika Johansson, Katherina Psarra, Serafeim Karathanos, Sergio Matarraz, Enrique Colado, European LeukemiaNet International MDS-Flow Cytometry Working Group (ELN iMDS-Flow), Monali Gupta, Robin Ireland, Wolfgang Kern, Arjan A. van de Loosdrecht

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: It was proposed that peripheral blood (PB) monocyte profiles evaluated by flow cytometry, called “monocyte assay,” could rapidly and efficiently distinguish chronic myelomonocytic leukemia (CMML) from other causes of monocytosis by highlighting an increase in the classical monocyte (cMo) fraction above 94%. However, the robustness of this assay requires a large multicenter validation and the assessment of its feasibility on bone marrow (BM) samples, as some centers may not have access to PB. Methods: PB and/or BM samples from patients displaying monocytosis were assessed with the “monocyte assay” by 10 ELN iMDS Flow working group centers with harmonized protocols. The corresponding files were reanalyzed in a blind fashion and the cMo percentages obtained by both analyses were compared. Confirmed diagnoses were collected when available. Results: The comparison between cMo percentages from 267 PB files showed a good global significant correlation (r = 0.88) with no bias. Confirmed diagnoses, available for 212 patients, achieved a 94% sensitivity and an 84% specificity. Hence, 95/101 CMML patients displayed cMo ≥94% while cMo <94% was observed in 83/99 patients with reactive monocytosis and in 10/12 patients with myeloproliferative neoplasms (MPN) with monocytosis. The established Receiver Operator Curve again provided a 94% cut-off value of cMo. The 117 BM files reanalysis led to an 87% sensitivity and an 80% specificity, with excellent correlation between the 43 paired samples to PB. Conclusions: This ELN multicenter study demonstrates the robustness of the monocyte assay with only limited variability of cMo percentages, validates the 94% cutoff value, confirms its high sensitivity and specificity in PB and finally, also confirms the possibility of its use in BM samples.

Original languageEnglish
JournalCytometry Part B - Clinical Cytometry
Early online date2021
DOIs
Publication statusE-pub ahead of print - 2021

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