Cancers (Dec 2021)
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,
- Janos Kappelmayer,
- Ester Mejstrikova,
- Leonid Karawajew,
- Jorge Rossi,
- Adın Çınar Suzan,
- Evangelina Agriello,
- Theodora Anastasiou-Grenzelia,
- Virna Barcala,
- Gábor Barna,
- Drago Batinić,
- Jean-Pierre Bourquin,
- Monika Brüggemann,
- Karolina Bukowska-Strakova,
- Hasan Burnusuzov,
- Daniela Carelli,
- Günnur Deniz,
- Klara Dubravčić,
- Tamar Feuerstein,
- Marie Isabel Gaillard,
- Adriana Galeano,
- Hugo Giordano,
- Alejandro Gonzalez,
- Stefanie Groeneveld-Krentz,
- Zsuzsanna Hevessy,
- Ondrej Hrusak,
- 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,
- Alexander Popov,
- Richard Ratei,
- Cecilia Rodríguez,
- Elisa Olga Sajaroff,
- Simona Sala,
- Gordana Samardzija,
- Mary Sartor,
- Pamela Scarparo,
- Łukasz Sędek,
- Bojana Slavkovic,
- Liliana Solari,
- Peter Svec,
- Tomasz Szczepanski,
- Anna Taparkou,
- Montserrat Torrebadell,
- Marianna Tzanoudaki,
- Elena Varotto,
- Helly Vernitsky,
- Andishe Attarbaschi,
- Martin Schrappe,
- Valentino Conter,
- Andrea Biondi,
- Marisa Felice,
- Myriam Campbell,
- Csongor Kiss,
- Giuseppe Basso,
- Michael N. Dworzak,
- on behalf of I-BFM-FLOW-Network
Affiliations
- Margarita Maurer-Granofszky
- Children’s Cancer Research Institute, Medical University of Vienna, 1090 Vienna, Austria
- Angela Schumich
- Children’s Cancer Research Institute, Medical University of Vienna, 1090 Vienna, Austria
- Barbara Buldini
- Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, University of Padova, 35122 Padova, Italy
- Giuseppe Gaipa
- M. Tettamanti Foundation Research Center, Department of Pediatrics, University of Milano-Bicocca, 20900 Monza, Italy
- Janos Kappelmayer
- Department of Laboratory Medicine, University of Debrecen, 4032 Debrecen, Hungary
- Ester Mejstrikova
- Department of Paediatric Haematology and Oncology, University Hospital Motol, 150 06 Prague, Czech Republic
- Leonid Karawajew
- Department of Pediatric Oncology and Hematology, Charité Berlin, 10117 Berlin, Germany
- Jorge Rossi
- Cellular Immunology Laboratory, Hospital de Pediatria “Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina
- Adın Çınar Suzan
- Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34452 Istanbul, Turkey
- Evangelina Agriello
- LEB Laboratorio, Servicio de Hematologia Hospital Penna, Bahia Blanca B8000, Argentina
- Theodora Anastasiou-Grenzelia
- P.&A. Kyriakou Children’s Hospital of Athens, 115 27 Athens, Greece
- Virna Barcala
- Laboratory—Flow Cytometry, Citomlab, Buenos Aires C1406AWK, Argentina
- Gábor Barna
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary
- Drago Batinić
- Division of Laboratory Immunology, Department of Laboratory Diagnostics, University Hospital Centre Zagreb & School of Medicine, 10000 Zagreb, Croatia
- Jean-Pierre Bourquin
- Department of Oncology and Children’s Cancer Research Center, University Children’s Hospital, 8032 Zurich, Switzerland
- Monika Brüggemann
- Department of Hematology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
- Karolina Bukowska-Strakova
- Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, 31-008 Krakow, Poland
- Hasan Burnusuzov
- Center of Competence “PERIMED”, Department of Pediatrics, Department of Microbiology and Clinical Immunology, Medical University Plovdiv, 4002 Plovdiv, Bulgaria
- Daniela Carelli
- Hospital Guillermo Rawson, San Juan J5400, Argentina
- Günnur Deniz
- Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34452 Istanbul, Turkey
- Klara Dubravčić
- Division of Laboratory Immunology, Department of Laboratory Diagnostics, University Hospital Centre Zagreb & School of Medicine, 10000 Zagreb, Croatia
- Tamar Feuerstein
- The Rina Zaizov Division of Pediatric Hematology-Oncology, Schneider’s Children’s Medical Center, Petah Tikva 4920235, Israel
- Marie Isabel Gaillard
- Bioquimica, Inmunologia, Hospital de Ninos Rocardo Gutierrez, Buenos Aires C1425EFD, Argentina
- Adriana Galeano
- Flow Cytometry Laboratory, FUNDALEU, Buenos Aires C1114, Argentina
- Hugo Giordano
- Fundación Pérez Scremini, Pediatric Hematology-Oncology Service, Pereira Rossell Hospital, Montevideo 11600, Uruguay
- Alejandro Gonzalez
- PAPSI Laboratorio Mendoza, Rosario S2000, Argentina
- Stefanie Groeneveld-Krentz
- Department of Pediatric Oncology and Hematology, Charité Berlin, 10117 Berlin, Germany
- Zsuzsanna Hevessy
- Department of Laboratory Medicine, University of Debrecen, 4032 Debrecen, Hungary
- Ondrej Hrusak
- Department of Paediatric Haematology and Oncology, University Hospital Motol, 150 06 Prague, Czech Republic
- Maria Belen Iarossi
- Flow Cytometry Laboratory, Provincial Histocompatibility Reference Centre, CUCAIBA, Buenos Aires C1114, Argentina
- Pál Jáksó
- Flow Cytometry Laboratory, Department of Pathology, Clinical Centre, University of Pécs, 7622 Pécs, Hungary
- Veronika Kloboves Prevodnik
- Department of Cytopathology, Institute of Oncology, 1000 Ljubljana, Slovenia
- Saskia Kohlscheen
- Department of Hematology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
- Elena Kreminska
- Clinical Laboratory Diagnostics and Metrology of NCSH “OHMATDYT”, Ministry of Heath of Ukraine, 01601 Kiev, Ukraine
- Oscar Maglia
- M. Tettamanti Foundation Research Center, Department of Pediatrics, University of Milano-Bicocca, 20900 Monza, Italy
- Cecilia Malusardi
- Hospital de Clinica Jose de San Martin, Buenos Aires C1120, Argentina
- Neda Marinov
- PINDA, Chilean National Pediatric Oncology Group, Hospital Roberto del Rio, Universidad de Chile, Santiago 8380418, Chile
- Bibiana Maria Martin
- Laboratorio CEBAC SRL, Posadas N3300, Argentina
- Claudia Möller
- Department of Oncology and Children’s Cancer Research Center, University Children’s Hospital, 8032 Zurich, Switzerland
- Sergey Nikulshin
- Hematopathology and Flow Cytometry Division, Children’s Clinical University Hospital, LV-1004 Riga, Latvia
- Jorge Palazzi
- IICT Labs, Rosario S2000, Argentina
- Georgios Paterakis
- Georgios Gennimatas General Hospital of Athens, 115 27 Athens, Greece
- Alexander Popov
- Laboratory of Leukemia Immunophenotyping, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia
- Richard Ratei
- Clinic for Hematology and Tumor Immunology, HELIOS Klinikum Berlin-Buch, 13125 Berlin, Germany
- Cecilia Rodríguez
- Hospital Nacional de Clínicas, Universidad Nacional de Córdoba, Cordoba X5000HUA, Argentina
- Elisa Olga Sajaroff
- Cellular Immunology Laboratory, Hospital de Pediatria “Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina
- Simona Sala
- M. Tettamanti Foundation Research Center, Department of Pediatrics, University of Milano-Bicocca, 20900 Monza, Italy
- Gordana Samardzija
- Laboratory for Flow Cytometry and Immunology, Institute for Health and Protection of Mother and Child of Serbia, 11070 Belgrade, Serbia
- Mary Sartor
- The Children’s Hospital at Westmead, Sydney, NSW 2145, Australia
- Pamela Scarparo
- Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, University of Padova, 35122 Padova, Italy
- Łukasz Sędek
- Department of Microbiology and Immunology, Medical University of Silesia, 40-055 Katowice, Poland
- Bojana Slavkovic
- Laboratory for Flow Cytometry and Immunology, Institute for Health and Protection of Mother and Child of Serbia, 11070 Belgrade, Serbia
- Liliana Solari
- Servicio de Bioquimica, Hospital Posadas, Buenos Aires B1684, Argentina
- Peter Svec
- National Institute of Children’s Diseases, 831 01 Bratislava, Slovakia
- Tomasz Szczepanski
- Department of Pediatric Hematology and Oncology, Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
- Anna Taparkou
- Department of Pediatric Oncology Hippokration General Hospital, 546 42 Thessaloniki, Greece
- Montserrat Torrebadell
- Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, 08950 Barcelona, Spain
- Marianna Tzanoudaki
- Department of Immunology & Histocompatibility, “Agia Sophia” Children’s Hospital, 115 27 Athens, Greece
- Elena Varotto
- Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, University of Padova, 35122 Padova, Italy
- Helly Vernitsky
- Hematology Lab, Sheba Medical Center, Ramat Gan 52621, Israel
- Andishe Attarbaschi
- St. Anna Children’s Hospital, Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria
- Martin Schrappe
- Department of Pediatrics, University Medical Center SchleswigHolstein, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany
- Valentino Conter
- Clinica Pediatrica University degli Studi di Milano Biococca, Fondazione MBBM, 20900 Monza, Italy
- Andrea Biondi
- Clinica Pediatrica University degli Studi di Milano Biococca, Fondazione MBBM, 20900 Monza, Italy
- Marisa Felice
- Department of Hematology and Oncology, Hospital de Pediatria “Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina
- Myriam Campbell
- PINDA, Chilean National Pediatric Oncology Group, Hospital Roberto del Rio, Universidad de Chile, Santiago 8380418, Chile
- Csongor Kiss
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
- Giuseppe Basso
- Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, University of Padova, 35122 Padova, Italy
- Michael N. Dworzak
- Children’s Cancer Research Institute, Medical University of Vienna, 1090 Vienna, Austria
- on behalf of I-BFM-FLOW-Network
- DOI
- https://doi.org/10.3390/cancers13236148
- Journal volume & issue
-
Vol. 13,
no. 23
p. 6148
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.
Keywords
