{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:39:42Z","timestamp":1789011582173,"version":"build-2803163510"},"reference-count":59,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The detection of minimal residual disease (MRD) has become part of the state-of-the-art diagnostics to guide treatment both in pediatric and adult acute lymphoblastic leukemia (ALL). This applies to the treatment of de novo and recurrent ALL. In high-risk ALL, MRD detection is considered an important tool to adjust therapy before and after hematopoietic stem cell transplantation. Precise quantification and quality control is instrumental to avoid false treatment assignment. A new methodological approach to analyzing MRD has become available and is based on next-generation sequencing. In principle, this technique will be able to detect a large number of leukemic subclones at a much higher speed than before. Carefully designed prospective studies need to demonstrate concordance or even superiority compared with those techniques in use right now: detection of aberrant expression of leukemia-specific antigens by flow cytometry of blood or bone marrow, or detection of specific rearrangements of the T-cell receptor or immunoglobulin genes by real-time quantitative polymerase chain reaction using DNA of leukemic cells. In some cases with known fusion genes, such as BCR\/ABL, reverse transcriptase-polymerase chain reaction has been used as additional method to identify leukemic cells by analyzing RNA in patient samples. MRD detection may be used to modulate treatment intensity once it has been demonstrated at well-defined informative checkpoints that certain levels of MRD can reliably predict the risk of relapse. In addition, MRD is used as end point to determine the activity of a given agent or treatment protocol. If activity translates into antileukemic efficacy, MRD may be considered a surrogate clinical end point.<\/jats:p>","DOI":"10.1182\/asheducation-2014.1.244","type":"journal-article","created":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T18:39:03Z","timestamp":1416854343000},"page":"244-249","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":45,"title":["Detection and management of minimal residual disease in acute lymphoblastic leukemia"],"prefix":"10.1182","volume":"2014","author":[{"given":"Martin","family":"Schrappe","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Christian-Albrechts-University of Kiel, University Medical Center Schleswig-Holstein, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"9","key":"2019111703180509600_B1","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1182\/blood-2007-09-112920","article-title":"Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95","volume":"111","author":"M\u00f6ricke","year":"2008","journal-title":"Blood"},{"issue":"3","key":"2019111703180509600_B2","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1182\/blood-2006-01-024729","article-title":"Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)","volume":"109","author":"Schultz","year":"2007","journal-title":"Blood"},{"issue":"15","key":"2019111703180509600_B3","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1056\/NEJMoa1110169","article-title":"Outcomes after induction failure in childhood acute lymphoblastic leukemia","volume":"366","author":"Schrappe","year":"2012","journal-title":"N Engl J Med"},{"issue":"7","key":"2019111703180509600_B4","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3324\/haematol.2011.047613","article-title":"Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the trial ALL-BFM 95: differential effects in precursor B-cell and T-cell leukemia","volume":"97","author":"Lauten","year":"2012","journal-title":"Haematologica"},{"issue":"3","key":"2019111703180509600_B5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/leu.2009.268","article-title":"Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008","volume":"24","author":"Bruggemann","year":"2010","journal-title":"Leukemia"},{"issue":"4","key":"2019111703180509600_B6","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/sj.leu.2404586","article-title":"Analysis of minimal residual disease by Ig\/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data","volume":"21","author":"van der Velden","year":"2007","journal-title":"Leukemia"},{"issue":"4","key":"2019111703180509600_B7","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/leu.2008.5","article-title":"Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia","volume":"22","author":"Flohr","year":"2008","journal-title":"Leukemia"},{"issue":"12","key":"2019111703180509600_B8","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1182\/blood-2008-01-132837","article-title":"Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study","volume":"111","author":"Borowitz","year":"2008","journal-title":"Blood"},{"issue":"31","key":"2019111703180509600_B9","doi-asserted-by":"crossref","first-page":"5168","DOI":"10.1200\/JCO.2008.20.8934","article-title":"Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow","volume":"27","author":"Basso","year":"2009","journal-title":"J Clin Oncol"},{"issue":"1","key":"2019111703180509600_B10","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1182\/blood-2006-01-0066","article-title":"A simplified flow cytometric assay identifies children with acute lymphoblastic leukemia who have a superior clinical outcome","volume":"108","author":"Coustan-Smith","year":"2006","journal-title":"Blood"},{"issue":"9","key":"2019111703180509600_B11","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1056\/NEJM199808273390904","article-title":"Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. 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