{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T02:14:34Z","timestamp":1787796874684,"version":"build-2784847793"},"reference-count":37,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The sensitivity of conventional techniques for reliable quantification of minimal\/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) is limited to MRD 10\u22124. Measuring MRD &amp;lt;10\u22124 could help to further distinguish between patients with CLL with durable remission and those at risk of early relapse. We herein present an academically developed immunoglobulin heavy-chain variable (IGHV) leader-based next-generation sequencing (NGS) assay for the quantification of MRD in CLL. We demonstrate, based on measurements in contrived MRD samples, that the linear range of detection and quantification of our assay reaches beyond MRD 10\u22125. If provided with sufficient DNA input, MRD can be detected down to MRD 10\u22126. There was high interassay concordance between measurements of the IGHV leader-based NGS assay and allele-specific oligonucleotide quantitative polymerase chain reaction (PCR) (r\u00a0= 0.92 [95% confidence interval {CI}, 0.86-0.96]) and droplet digital PCR (r\u00a0=\u00a00.93 [95% CI, 0.88-0.96]) on contrived MRD samples. In a cohort of 67 patients from the CLL11 trial, using MRD 10\u22125 as a cutoff, undetectable MRD was associated with superior progression-free survival (PFS) and time to next treatment. More important, deeper MRD measurement allowed for additional stratification of patients with MRD &amp;lt;10\u22124 but \u226510\u22125. PFS of patients in this MRD range was significantly shorter, compared with patients with MRD &amp;lt;10\u22125 (hazard ratio [HR], 4.0 [95% CI, 1.6-10.3]; P\u00a0= .004), but significantly longer, compared with patients with MRD \u226510\u22124 (HR, 0.44 [95% CI, 0.23-0.87]; P\u00a0= .018). These results support the clinical utility of the IGHV leader-based NGS assay.<\/jats:p>","DOI":"10.1182\/blood.2022017411","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T21:04:19Z","timestamp":1662757459000},"page":"519-528","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["Detecting measurable residual disease beyond 10\u22124 by an IGHV leader-based NGS approach improves prognostic stratification in CLL"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-138X","authenticated-orcid":false,"given":"Paul J.","family":"Hengeveld","sequence":"first","affiliation":[{"name":"1Laboratory of Medical Immunology, Department of Immunology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands"},{"name":"2Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le Y.","family":"van der Klift","sequence":"additional","affiliation":[{"name":"1Laboratory of Medical Immunology, Department of Immunology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Martijn","family":"Kolijn","sequence":"additional","affiliation":[{"name":"1Laboratory of Medical Immunology, Department of Immunology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Davi","sequence":"additional","affiliation":[{"name":"3Department of Hematology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, University of Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois G.","family":"Kavelaars","sequence":"additional","affiliation":[{"name":"4Department of Hematology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evert","family":"de Jonge","sequence":"additional","affiliation":[{"name":"5Department of Clinical Chemistry, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Robrecht","sequence":"additional","affiliation":[{"name":"6Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6947-8905","authenticated-orcid":false,"given":"Jorn L. J. C.","family":"Assmann","sequence":"additional","affiliation":[{"name":"1Laboratory of Medical Immunology, Department of Immunology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"van der Straten","sequence":"additional","affiliation":[{"name":"1Laboratory of Medical Immunology, Department of Immunology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands"},{"name":"2Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Ritgen","sequence":"additional","affiliation":[{"name":"7Department of Medicine II, University Hospital of Schleswig Holstein, Campus Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Westerweel","sequence":"additional","affiliation":[{"name":"2Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Fischer","sequence":"additional","affiliation":[{"name":"6Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Goede","sequence":"additional","affiliation":[{"name":"8Division of Oncogeriatrics, St Marien Hospital, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-063X","authenticated-orcid":false,"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[{"name":"6Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark-David","family":"Levin","sequence":"additional","affiliation":[{"name":"2Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-3220","authenticated-orcid":false,"given":"Anton W.","family":"Langerak","sequence":"additional","affiliation":[{"name":"1Laboratory of Medical Immunology, Department of Immunology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"9","key":"2023082817150130800_bib1","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1200\/JCO.2011.36.9348","article-title":"Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate 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