{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:11:22Z","timestamp":1772118682487,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T00:00:00Z","timestamp":1565913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["MCO\u201010007"],"award-info":[{"award-number":["MCO\u201010007"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["N\u00b0 21198"],"award-info":[{"award-number":["N\u00b0 21198"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In 2009, the four laboratories of the Fondazione Italiana Linfomi (FIL) minimal residual disease (MRD) Network started a collaborative effort to harmonize and standardize their methodologies at the national level, performing quality control (QC) rounds for follicular lymphoma (FL) and mantle cell lymphoma (MCL) MRD assessment. In 16 QC rounds between 2010 and 2017, the four laboratories received 208 bone marrow (BM) samples (126 FL; 82 MCL); 187 were analyzed, according to the EuroMRD Consortium guidelines, by both nested (NEST) polymerase chain reaction (PCR) and real\u2010time quantitative (RQ) PCR for\n                    <jats:italic>BCL2\/IGH MBR<\/jats:italic>\n                    or\n                    <jats:italic>IGHV<\/jats:italic>\n                    rearrangements. Here, we aimed at analyzing the samples that challenged the interlaboratory reproducibility and data interpretation. Overall, 156\/187 BM samples (83%) were concordantly classified as NEST+\/RQ+ or NEST\u2212\/RQ\u2212 by all the four laboratories. The remaining 31 samples (17%) resulted alternatively positive and negative in the interlaboratory evaluations, independently of the method and the type of rearrangement, and were defined \u201cborderline\u201d (brd) samples: 12 proved NEST brd\/RQ brd, 7 NEST\u2212\/RQ brd, 10 NEST brd\/RQ positive not quantifiable (PNQ), and 2 NEST brd\/RQ\u2212. Results did not change even increasing the number of replicates\/sample. In 6\/31 brd samples, droplet digital PCR (ddPCR) was tested and showed no interlaboratory discordance. Despite the high interlaboratory reproducibility in the MRD analysis obtained and maintained by the QC round strategy, samples with the lowest MRD levels can still represent a challenge: 17% (31\/187) of our samples showed discordant results in interlaboratory assessments, with 6.4% (12\/187) remained brd even applying the two methods. Thus, although representing a minority, brd samples are still problematic, especially when a clinically oriented interpretation of MRD results is required. Alternative, novel methods such as ddPCR and next\u2010generation sequencing have the potential to overcome the current limitations.\n                  <\/jats:p>","DOI":"10.1002\/hon.2652","type":"journal-article","created":{"date-parts":[[2019,7,20]],"date-time":"2019-07-20T00:30:01Z","timestamp":1563582601000},"page":"368-374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Minimal residual disease (MRD) in non\u2010Hodgkin lymphomas: Interlaboratory reproducibility on marrow samples with very low levels of disease within the FIL (Fondazione Italiana Linfomi) MRD Network"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7909-8642","authenticated-orcid":false,"given":"Irene","family":"Della Starza","sequence":"first","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine \u201cSapienza\u201d University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzia","family":"Cavalli","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine \u201cSapienza\u201d University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia Anna","family":"De Novi","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine \u201cSapienza\u201d University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Genuardi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnologies and Health Sciences, Division of Hematology University of Torino  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Mantoan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnologies and Health Sciences, Division of Hematology University of Torino  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Drandi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnologies and Health Sciences, Division of Hematology University of Torino  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Barbero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnologies and Health Sciences, Division of Hematology University of Torino  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Ciabatti","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Oncology Santa Chiara Hospital  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Grassi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena  Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Gazzola","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola\u2010Malpighi Hospital University of Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Mannu","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola\u2010Malpighi Hospital University of Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Agostinelli","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola\u2010Malpighi Hospital University of Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Paolo","family":"Piccaluga","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola\u2010Malpighi Hospital University of Bologna  Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Bomben","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Onco\u2010Haematology Unit Centro di Riferimento Oncologico, I.R.C.C.S.  Aviano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Degan","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Onco\u2010Haematology Unit Centro di Riferimento Oncologico, I.R.C.C.S.  Aviano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valter","family":"Gattei","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Onco\u2010Haematology Unit Centro di Riferimento Oncologico, I.R.C.C.S.  Aviano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Guarini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine \u201cSapienza\u201d University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Fo\u00e0","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine \u201cSapienza\u201d University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Oncology Santa Chiara Hospital  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Ladetto","sequence":"additional","affiliation":[{"name":"Division of Hematology Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo  Alessandria Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnologies and Health Sciences, Division of Hematology University of Torino  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Del Giudice","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine \u201cSapienza\u201d University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Fondazione Italiana Linfomi (FIL) MRD Network","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402922"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-248146"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2708"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-230250"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.10.054"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-116749"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-507319"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0407"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw419"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-269-8_10"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404586"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-07-655159"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000563528.69483.e1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.12.3449.3449"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(00)00651-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14616"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2015.05.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14082"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403202"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1083-8791(00)70006-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.8.2651"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2095"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040620713480522"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6.10.995"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.268"},{"issue":"1","key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1182\/blood-2018-99-114442","article-title":"Comprehensive minimal residual disease (MRD) analysis of the Fondazione Italiana Linfomi (FIL) MCL0208 clinical trial for younger patients with mantle cell lymphoma: a kinetic model ensures a more refined risk stratification. 60th ASH Annual Meeting and Exposition, San Diego, December 1\u20104, 2018","volume":"132","author":"Ferrero S","year":"2018","journal-title":"Blood"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00363"},{"key":"e_1_2_9_29_1","first-page":"S1","article-title":"Minimal residual disease (MRD) detection by digital\u2010droplet\u2010pcr (ddPCR) in lymphoid malignancies. 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