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
Margarita Maurer‐Granofszky, Angela Schumich, Barbara Buldini, Giuseppe Gaipa, János Kappelmayer, Ester Mejstříková, Leonid Karawajew, Jorge G. Rossi, Adın Çınar Suzan, Evangelina Agriello, Theodora Anastasiou-Grenzelia, Virna Barcala, Gábor Barna, Drago Batinić, Jean‐Pierre Bourquin, Monika Brüggemann, Karolina Bukowska-Straková, Hasan Burnusuzov, Daniela Carelli, Günnur Deniz, Klara Dubravčić, Tamar Feuerstein, M. Gaillard, Adriana Galeano, Hugo Giordano, Alejandro González, Stefanie Groeneveld‐Krentz, Zsuzsanna Hevessy, Ondřej Hrušák, Maria Belen Iarossi, Pál Jáksó, Veronika Kloboves Prevodnik, Saskia Kohlscheen, Elena Kreminska, Oscar Maglia, Cecilia Malusardi, Neda Marinov, Bibiana Maria Martin, Claudia Möller, Sergey Nikulshin, Jorge Palazzi, Georgios Paterakis, А. М. Попов, Richard Ratei, Cecilia Rodríguez, Elisa O. Sajaroff, Simona Sala, Gordana Samardžija, Mary Sartor, Pamela Scarparo, Łukasz Sędek, Bojana Slavković, Liliana Solari, Peter Švec, Tomasz Szczepański, Άννα Ταπάρκου, Montserrat Torrebadell, Marianna Tzanoudaki, Elena Varotto, Helly Vernitsky, Andishe Attarbaschi, Martin Schrappe, Valentino Conter, Andrea Biondi, Marı́a Sara Felice, Myriam Campbell, Csongor Kiss, Giuseppe Basso, Michael Dworzak, on behalf of I-BFM-FLOW-Network
Abstract
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.