{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:34:29Z","timestamp":1781224469046,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T00:00:00Z","timestamp":1640908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Minimal residual disease (MRD) measured on end\u2010of\u2010induction bone marrow (BM) is the most important biomarker for guiding therapy in pediatric acute lymphoblastic leukemia (ALL). Due to limited sensitivity of current approaches, peripheral blood (PB) is not a reliable source for identifying patients needing treatment changes. We sought to determine if high\u2010throughput sequencing (HTS) (next\u2010generation sequencing) of rearranged immunoglobulin and T\u2010cell receptor genes can overcome this and be used to measure MRD in PB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>We employed a quantitative HTS approach to accurately measure MRD from one million cell equivalents of DNA from 17 PB samples collected at day 29 after induction therapy in patients with precursor B\u2010cell ALL. We compared these results to the gold\u2010standard real\u2010time PCR result obtained from their paired BM samples, median follow\u2010up 49 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With the increased sensitivity, detecting up to one abnormal cell in a million normal cells, we were able to detect MRD in the PB by HTS in all those patients requiring treatment intensification (MRD \u2265 0.005% in BM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is proof of principle that using the increased sensitivity of HTS, PB can be used to measure MRD and stratify children with ALL. The method is cost effective, rapid, accurate, and reproducible, with inherent advantages in children. Importantly, increasing the frequency testing by PB as opposed to intermittent BM sampling may allow extension of the dynamic range of MRD, giving a more complete picture of the kinetics of disease remission while improving relapse prediction and speed of detection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29513","type":"journal-article","created":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T11:32:06Z","timestamp":1640950326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["High\u2010throughput sequencing of peripheral blood for minimal residual disease monitoring in childhood precursor B\u2010cell acute lymphoblastic leukemia: A prospective feasibility study"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1573-2506","authenticated-orcid":false,"given":"Jack","family":"Bartram","sequence":"first","affiliation":[{"name":"Depatment of Haematology, Great Ormond Street Hospital for Children  London UK"},{"name":"Cancer Section, Institute of Child Health, University College London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Wright","sequence":"additional","affiliation":[{"name":"Depatment of Haematology, Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Adams","sequence":"additional","affiliation":[{"name":"Depatment of Haematology, Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Archer","sequence":"additional","affiliation":[{"name":"Bristol Genetics Laboratory, Southmead Hospital, North Bristol NHS Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Brooks","sequence":"additional","affiliation":[{"name":"UCL Genomics, Institute of Child Health, University College London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Edwards","sequence":"additional","affiliation":[{"name":"Cancer Section, Institute of Child Health, University College London  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Hancock","sequence":"additional","affiliation":[{"name":"Bristol Genetics Laboratory, Southmead Hospital, North Bristol NHS Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Knecht","sequence":"additional","affiliation":[{"name":"Department of Hematology University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Inglott","sequence":"additional","affiliation":[{"name":"Depatment of Haematology, Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Mountjoy","sequence":"additional","affiliation":[{"name":"School of Social and Community Medicine, University of Bristol  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Roynane","sequence":"additional","affiliation":[{"name":"Depatment of Haematology, Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Wakeman","sequence":"additional","affiliation":[{"name":"Bristol Genetics Laboratory, Southmead Hospital, North Bristol NHS Trust  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Moppett","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology\/Oncology, Royal Hospital for Children  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Hubank","sequence":"additional","affiliation":[{"name":"Centre for Molecular Pathology, The Royal Marsden  Sutton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Goulden","sequence":"additional","affiliation":[{"name":"Depatment of Haematology, Great Ormond Street Hospital for Children  London UK"},{"name":"Trapehade, Monferran\u2010Plav\u00e8s  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0580"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.40.5936"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70600-9"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-248146"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2015-309617"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.00574.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)04058-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2009.07.010"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21101"},{"key":"e_1_2_10_11_1","article-title":"Minimal residual disease (MRD) diagnostics in acute lymphoblastic leukemia (ALL): need for sensitive, fast and standardized technologies","author":"Dongen JJ","year":"2015","journal-title":"Blood"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.04.018"},{"key":"e_1_2_10_13_1","article-title":"Measurable residual disease detection by high throughput sequencing improves risk stratification for pediatric B\u2010ALL","author":"Wood B","year":"2017","journal-title":"Blood"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.02.008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.3723186.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402268"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1130"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23081"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01715137"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402636"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1994.tb04812.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00377"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-444042"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003656"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3231"},{"issue":"6","key":"e_1_2_10_26_1","first-page":"695","article-title":"IMGT\/V\u2010QUEST: IMGT standardized analysis of the immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences","volume":"2011","author":"Giudicelli V","year":"2011","journal-title":"Cold Spring Harb Protoc"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404586"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70066-8"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.142"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.7.2315"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2009.080047"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-067785"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1455"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-12-615757"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29513","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.29513","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29513","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T06:21:55Z","timestamp":1693203715000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.29513"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,31]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/pbc.29513"],"URL":"https:\/\/doi.org\/10.1002\/pbc.29513","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,31]]},"assertion":[{"value":"2021-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29513"}}