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


Por: Maurer-Granofszky M, Schumich A, Buldini B, Gaipa G, Kappelmayer J, Mejstrikova E, Karawajew L, Rossi J, Suzan AÇ, Agriello E, Anastasiou-Grenzelia T, Barcala V, Barna G, Batinic D, Bourquin JP, Brüggemann M, Bukowska-Strakova K, Burnusuzov H, Carelli D, Deniz G, Dubravcic K, Feuerstein T, Gaillard MI, Galeano A, Giordano H, Gonzalez A, Groeneveld-Krentz S, Hevessy Z, Hrusak O, Iarossi MB, Jáksó P, Kloboves Prevodnik V, Kohlscheen S, Kreminska E, Maglia O, Malusardi C, Marinov N, Martin BM, Möller C, Nikulshin S, Palazzi J, Paterakis G, Popov A, Ratei R, Rodríguez C, Sajaroff EO, Sala S, Samardzija G, Sartor M, Scarparo P, Sedek L, Slavkovic B, Solari L, Svec P, Szczepanski T, Taparkou A, Torrebadell-Burriel M, Tzanoudaki M, Varotto E, Vernitsky H, Attarbaschi A, Schrappe M, Conter V, Biondi A, Felice M, Campbell M, Kiss C, Basso G, Dworzak MN and On Behalf Of I-Bfm-Flow-Network

Publicada: 6 dic 2021 Ahead of Print: 6 dic 2021
Resumen:
Simple Summary Standardization of flow-cytometric assessment of minimal residual disease in acute lymphoid leukemia (ALL) is necessary to allow concordant multicentric application of the methodology. This is a prerequisite for internationally collaborative trials, such as the AIEOP-BFM-ALL and the ALL IC-BFM trial. We developed and applied a comprehensive training and quality control program involving a large number of international laboratories within the I-BFM consortium to complement standardization of the methodology with an educational component as well as with persistent quality control measures to allow large ALL treatment trials which use multi-laboratory FCM-MRD assessments for risk stratification of pediatric patients with ALL. 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-Munster (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.

Filiaciones:
Maurer-Granofszky M:
 Children's Cancer Research Institute, Medical University of Vienna, 1090 Vienna, Austria

Schumich A:
 Children's Cancer Research Institute, Medical University of Vienna, 1090 Vienna, Austria

Buldini B:
 Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, University of Padova, 35122 Padova, Italy

Gaipa G:
 M. Tettamanti Foundation Research Center, Department of Pediatrics, University of Milano-Bicocca, 20900 Monza, Italy

Kappelmayer J:
 Department of Laboratory Medicine, University of Debrecen, 4032 Debrecen, Hungary

Mejstrikova E:
 Department of Paediatric Haematology and Oncology, University Hospital Motol, 150 06 Prague, Czech Republic

Karawajew L:
 Department of Pediatric Oncology and Hematology, Charité Berlin, 10117 Berlin, Germany

Rossi J:
 Cellular Immunology Laboratory, Hospital de Pediatria "Dr. Juan P. Garrahan", Buenos Aires C1245, Argentina

Suzan AÇ:
 Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34452 Istanbul, Turkey

Agriello E:
 LEB Laboratorio, Servicio de Hematologia Hospital Penna, Bahia Blanca B8000, Argentina

Anastasiou-Grenzelia T:
 P.&A. Kyriakou Children's Hospital of Athens, 115 27 Athens, Greece

Barcala V:
 Laboratory-Flow Cytometry, Citomlab, Buenos Aires C1406AWK, Argentina

Barna G:
 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary

Batinic D:
 Division of Laboratory Immunology, Department of Laboratory Diagnostics, University Hospital Centre Zagreb & School of Medicine, 10000 Zagreb, Croatia

Bourquin JP:
 Department of Oncology and Children's Cancer Research Center, University Children's Hospital, 8032 Zurich, Switzerland

Brüggemann M:
 Department of Hematology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany

Bukowska-Strakova K:
 Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, 31-008 Krakow, Poland

Burnusuzov H:
 Center of Competence "PERIMED", Department of Pediatrics, Department of Microbiology and Clinical Immunology, Medical University Plovdiv, 4002 Plovdiv, Bulgaria

Carelli D:
 Hospital Guillermo Rawson, San Juan J5400, Argentina

Deniz G:
 Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34452 Istanbul, Turkey

Dubravcic K:
 Division of Laboratory Immunology, Department of Laboratory Diagnostics, University Hospital Centre Zagreb & School of Medicine, 10000 Zagreb, Croatia

Feuerstein T:
 The Rina Zaizov Division of Pediatric Hematology-Oncology, Schneider's Children's Medical Center, Petah Tikva 4920235, Israel

Gaillard MI:
 Bioquimica, Inmunologia, Hospital de Ninos Rocardo Gutierrez, Buenos Aires C1425EFD, Argentina

Galeano A:
 Flow Cytometry Laboratory, FUNDALEU, Buenos Aires C1114, Argentina

Giordano H:
 Fundación Pérez Scremini, Pediatric Hematology-Oncology Service, Pereira Rossell Hospital, Montevideo 11600, Uruguay

Gonzalez A:
 PAPSI Laboratorio Mendoza, Rosario S2000, Argentina

Groeneveld-Krentz S:
 Department of Pediatric Oncology and Hematology, Charité Berlin, 10117 Berlin, Germany

Hevessy Z:
 Department of Laboratory Medicine, University of Debrecen, 4032 Debrecen, Hungary

Hrusak O:
 Department of Paediatric Haematology and Oncology, University Hospital Motol, 150 06 Prague, Czech Republic

Iarossi MB:
 Flow Cytometry Laboratory, Provincial Histocompatibility Reference Centre, CUCAIBA, Buenos Aires C1114, Argentina

Jáksó P:
 Flow Cytometry Laboratory, Department of Pathology, Clinical Centre, University of Pécs, 7622 Pécs, Hungary

Kloboves Prevodnik V:
 Department of Cytopathology, Institute of Oncology, 1000 Ljubljana, Slovenia

 Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia

Kohlscheen S:
 Department of Hematology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany

Kreminska E:
 Clinical Laboratory Diagnostics and Metrology of NCSH "OHMATDYT", Ministry of Heath of Ukraine, 01601 Kiev, Ukraine

Maglia O:
 M. Tettamanti Foundation Research Center, Department of Pediatrics, University of Milano-Bicocca, 20900 Monza, Italy

Malusardi C:
 Hospital de Clinica Jose de San Martin, Buenos Aires C1120, Argentina

Marinov N:
 PINDA, Chilean National Pediatric Oncology Group, Hospital Roberto del Rio, Universidad de Chile, Santiago 8380418, Chile

Martin BM:
 Laboratorio CEBAC SRL, Posadas N3300, Argentina

Möller C:
 Department of Oncology and Children's Cancer Research Center, University Children's Hospital, 8032 Zurich, Switzerland

Nikulshin S:
 Hematopathology and Flow Cytometry Division, Children's Clinical University Hospital, LV-1004 Riga, Latvia

Palazzi J:
 IICT Labs, Rosario S2000, Argentina

Paterakis G:
 Georgios Gennimatas General Hospital of Athens, 115 27 Athens, Greece

Popov A:
 Laboratory of Leukemia Immunophenotyping, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia

Ratei R:
 Clinic for Hematology and Tumor Immunology, HELIOS Klinikum Berlin-Buch, 13125 Berlin, Germany

Rodríguez C:
 Hospital Nacional de Clínicas, Universidad Nacional de Córdoba, Cordoba X5000HUA, Argentina

Sajaroff EO:
 Cellular Immunology Laboratory, Hospital de Pediatria "Dr. Juan P. Garrahan", Buenos Aires C1245, Argentina

Sala S:
 M. Tettamanti Foundation Research Center, Department of Pediatrics, University of Milano-Bicocca, 20900 Monza, Italy

Samardzija G:
 Laboratory for Flow Cytometry and Immunology, Institute for Health and Protection of Mother and Child of Serbia, 11070 Belgrade, Serbia

Sartor M:
 The Children's Hospital at Westmead, Sydney, NSW 2145, Australia

Scarparo P:
 Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, University of Padova, 35122 Padova, Italy

Sedek L:
 Department of Microbiology and Immunology, Medical University of Silesia, 40-055 Katowice, Poland

Slavkovic B:
 Laboratory for Flow Cytometry and Immunology, Institute for Health and Protection of Mother and Child of Serbia, 11070 Belgrade, Serbia

Solari L:
 Servicio de Bioquimica, Hospital Posadas, Buenos Aires B1684, Argentina

Svec P:
 National Institute of Children's Diseases, 831 01 Bratislava, Slovakia

Szczepanski T:
 Department of Pediatric Hematology and Oncology, Zabrze, Medical University of Silesia, 40-055 Katowice, Poland

Taparkou A:
 Department of Pediatric Oncology Hippokration General Hospital, 546 42 Thessaloniki, Greece

Torrebadell-Burriel M:
 Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, 08950 Barcelona, Spain

Tzanoudaki M:
 Department of Immunology & Histocompatibility, "Agia Sophia" Children's Hospital, 115 27 Athens, Greece

Varotto E:
 Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, University of Padova, 35122 Padova, Italy

Vernitsky H:
 Hematology Lab, Sheba Medical Center, Ramat Gan 52621, Israel

Attarbaschi A:
 St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria

Schrappe M:
 Department of Pediatrics, University Medical Center SchleswigHolstein, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany

Conter V:
 Clinica Pediatrica University degli Studi di Milano Biococca, Fondazione MBBM, 20900 Monza, Italy

Biondi A:
 Clinica Pediatrica University degli Studi di Milano Biococca, Fondazione MBBM, 20900 Monza, Italy

Felice M:
 Department of Hematology and Oncology, Hospital de Pediatria "Dr. Juan P. Garrahan", Buenos Aires C1245, Argentina

Campbell M:
 PINDA, Chilean National Pediatric Oncology Group, Hospital Roberto del Rio, Universidad de Chile, Santiago 8380418, Chile

Kiss C:
 Division of Pediatric Hematology-Oncology, Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary

Basso G:
 Pediatric Hematology, Oncology and Stem Cell Transplant Division, Maternal and Child Health Department, University of Padova, 35122 Padova, Italy

Dworzak MN:
 Children's Cancer Research Institute, Medical University of Vienna, 1090 Vienna, Austria

 St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria
ISSN: 20726694
Editorial
MDPI, MDPI AG, Grosspeteranlage 5, CH-4052 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 13 Número: 23
Páginas: 6148
WOS Id: 000740524800001
ID de PubMed: 34885257
imagen Green Published, Green Accepted, gold

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