An Extensive Quality Control and Quality Assurance (QC/QA) Program Significantly Improves Inter-Laboratory Concordance Rates of Flow-Cytometric Minimal Residual Disease Assessment in Acute Lymphoblastic Leukemia: An I-BFM-FLOW-Network Report
Authors: Maurer-Granofszky Margarita , Schumich Angela , Buldini Barbara , Gaipa Giuseppe , Kappelmayer Janos , Mejstrikova Ester , Karawajew Leonid , Rossi Jorge , Suzan Adın Çınar , Agriello Evangelina , Anastasiou-Grenzelia Theodora , Barcala Virna , Barna Gábor , Batinić Drago , Bourquin Jean-Pierre , Brüggemann Monika , Bukowska-Strakova Karolina , Burnusuzov Hasan , Carelli Daniela , Deniz Günnur , Dubravčić Klara , Feuerstein Tamar , Gaillard Marie Isabel , Galeano Adriana , Giordano Hugo , Gonzalez Alejandro , Groeneveld-Krentz Stefanie , Hevessy Zsuzsanna , Hrusak Ondrej , Iarossi Maria Belen , Jáksó Pál , Kloboves Prevodnik Veronika , Kohlscheen Saskia , Kreminska Elena , Maglia Oscar , Malusardi Cecilia , Marinov Neda , Martin Bibiana Maria , Möller Claudia , Nikulshin Sergey , Palazzi Jorge , Paterakis Georgios , Popov Alexander , Ratei Richard , Rodríguez Cecilia , Sajaroff Elisa Olga , Sala Simona , Samardzija Gordana , Sartor Mary , Scarparo Pamela , Sędek Łukasz , Slavkovic Bojana , Solari Liliana , Svec Peter , Szczepanski Tomasz , Taparkou Anna , Torrebadell Montserrat , Tzanoudaki Marianna , Varotto Elena , Vernitsky Helly , Attarbaschi Andishe , Schrappe Martin , Conter Valentino , Biondi Andrea , Felice Marisa , Campbell Myriam , Kiss Csongor , Basso Giuseppe , Dworzak Michael N. ,   on behalf of I-BFM-FLOW-Network
Published: December 2021

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.