Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction
Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-...
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creator | Cheng, Suk Hang Lau, Kin Mang Li, Chi Kong Chan, Natalie P H Ip, Rosalina K L Cheng, Chi Keung Lee, Vincent Shing, Matthew M K Leung, Alex W K Ha, Shau Yin Cheuk, Daniel K L Lee, Anselm C W Li, Chak Ho Luk, Chung Wing Ling, Siu Cheung Hrusak, Ondrej Mejstrikova, Ester Leung, Yonna Ng, Margaret H L |
description | Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: 10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15 |
doi_str_mv | 10.1371/journal.pone.0069467 |
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In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1-10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4) were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4). We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069467</identifier><identifier>PMID: 23936021</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute lymphoblastic leukemia ; Acute lymphocytic leukemia ; Adolescent ; Antigens ; Antineoplastic Agents - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; Biology ; Blood ; Blood plasma ; Bone marrow ; Cancer genetics ; Cancer research ; Cancer therapies ; Child ; Child, Preschool ; Childhood ; Children ; Cytometry ; Deoxyribonucleic acid ; Disease-Free Survival ; DNA ; DNA, Neoplasm - genetics ; Female ; Flow Cytometry ; Gating ; Health risks ; Hematology ; Humans ; Infant ; Invasiveness ; Leukemia ; Lymphatic leukemia ; Male ; Mathematical models ; Medical prognosis ; Medicine ; Minimal residual disease ; Monitoring ; Multivariate analysis ; Neoplasm, Residual ; Oncogene Proteins, Fusion - genetics ; Oncology ; Pathology ; Patients ; Pediatrics ; Peripheral blood ; Plasma ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Predictions ; Prognosis ; Quantitation ; Recurrence ; Risk ; Risk factors ; Risk groups ; Stem cell transplantation</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e69467-e69467</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Cheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Cheng et al 2013 Cheng et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ab026057192747e07043c8996acb38287ce3d50908db816cdf3b10709658ffca3</citedby><cites>FETCH-LOGICAL-c692t-ab026057192747e07043c8996acb38287ce3d50908db816cdf3b10709658ffca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723913/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723913/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23936021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Suk Hang</creatorcontrib><creatorcontrib>Lau, Kin Mang</creatorcontrib><creatorcontrib>Li, Chi Kong</creatorcontrib><creatorcontrib>Chan, Natalie P H</creatorcontrib><creatorcontrib>Ip, Rosalina K L</creatorcontrib><creatorcontrib>Cheng, Chi Keung</creatorcontrib><creatorcontrib>Lee, Vincent</creatorcontrib><creatorcontrib>Shing, Matthew M K</creatorcontrib><creatorcontrib>Leung, Alex W K</creatorcontrib><creatorcontrib>Ha, Shau Yin</creatorcontrib><creatorcontrib>Cheuk, Daniel K L</creatorcontrib><creatorcontrib>Lee, Anselm C W</creatorcontrib><creatorcontrib>Li, Chak Ho</creatorcontrib><creatorcontrib>Luk, Chung Wing</creatorcontrib><creatorcontrib>Ling, Siu Cheung</creatorcontrib><creatorcontrib>Hrusak, Ondrej</creatorcontrib><creatorcontrib>Mejstrikova, Ester</creatorcontrib><creatorcontrib>Leung, Yonna</creatorcontrib><creatorcontrib>Ng, Margaret H L</creatorcontrib><title>Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1-10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4) were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4). We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.</description><subject>Acute lymphoblastic leukemia</subject><subject>Acute lymphocytic leukemia</subject><subject>Adolescent</subject><subject>Antigens</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols</subject><subject>Biology</subject><subject>Blood</subject><subject>Blood plasma</subject><subject>Bone marrow</subject><subject>Cancer genetics</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Childhood</subject><subject>Children</subject><subject>Cytometry</subject><subject>Deoxyribonucleic acid</subject><subject>Disease-Free Survival</subject><subject>DNA</subject><subject>DNA, Neoplasm - genetics</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Gating</subject><subject>Health risks</subject><subject>Hematology</subject><subject>Humans</subject><subject>Infant</subject><subject>Invasiveness</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Male</subject><subject>Mathematical models</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Minimal residual disease</subject><subject>Monitoring</subject><subject>Multivariate analysis</subject><subject>Neoplasm, Residual</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Peripheral blood</subject><subject>Plasma</subject><subject>Polymerase Chain Reaction</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</subject><subject>Predictions</subject><subject>Prognosis</subject><subject>Quantitation</subject><subject>Recurrence</subject><subject>Risk</subject><subject>Risk factors</subject><subject>Risk groups</subject><subject>Stem cell 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residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction</title><author>Cheng, Suk Hang ; Lau, Kin Mang ; Li, Chi Kong ; Chan, Natalie P H ; Ip, Rosalina K L ; Cheng, Chi Keung ; Lee, Vincent ; Shing, Matthew M K ; Leung, Alex W K ; Ha, Shau Yin ; Cheuk, Daniel K L ; Lee, Anselm C W ; Li, Chak Ho ; Luk, Chung Wing ; Ling, Siu Cheung ; Hrusak, Ondrej ; Mejstrikova, Ester ; Leung, Yonna ; Ng, Margaret H L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-ab026057192747e07043c8996acb38287ce3d50908db816cdf3b10709658ffca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Acute lymphocytic leukemia</topic><topic>Adolescent</topic><topic>Antigens</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols</topic><topic>Biology</topic><topic>Blood</topic><topic>Blood plasma</topic><topic>Bone marrow</topic><topic>Cancer genetics</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Childhood</topic><topic>Children</topic><topic>Cytometry</topic><topic>Deoxyribonucleic acid</topic><topic>Disease-Free Survival</topic><topic>DNA</topic><topic>DNA, Neoplasm - genetics</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Gating</topic><topic>Health risks</topic><topic>Hematology</topic><topic>Humans</topic><topic>Infant</topic><topic>Invasiveness</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Male</topic><topic>Mathematical models</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Minimal residual disease</topic><topic>Monitoring</topic><topic>Multivariate analysis</topic><topic>Neoplasm, 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Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Suk Hang</au><au>Lau, Kin Mang</au><au>Li, Chi Kong</au><au>Chan, Natalie P H</au><au>Ip, Rosalina K L</au><au>Cheng, Chi Keung</au><au>Lee, Vincent</au><au>Shing, Matthew M K</au><au>Leung, Alex W K</au><au>Ha, Shau Yin</au><au>Cheuk, Daniel K L</au><au>Lee, Anselm C W</au><au>Li, Chak Ho</au><au>Luk, Chung Wing</au><au>Ling, Siu Cheung</au><au>Hrusak, Ondrej</au><au>Mejstrikova, Ester</au><au>Leung, Yonna</au><au>Ng, Margaret H L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-25</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e69467</spage><epage>e69467</epage><pages>e69467-e69467</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1-10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4) were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4). We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23936021</pmid><doi>10.1371/journal.pone.0069467</doi><tpages>e69467</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2013-07, Vol.8 (7), p.e69467-e69467 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1427813822 |
source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Acute lymphoblastic leukemia Acute lymphocytic leukemia Adolescent Antigens Antineoplastic Agents - administration & dosage Antineoplastic Combined Chemotherapy Protocols Biology Blood Blood plasma Bone marrow Cancer genetics Cancer research Cancer therapies Child Child, Preschool Childhood Children Cytometry Deoxyribonucleic acid Disease-Free Survival DNA DNA, Neoplasm - genetics Female Flow Cytometry Gating Health risks Hematology Humans Infant Invasiveness Leukemia Lymphatic leukemia Male Mathematical models Medical prognosis Medicine Minimal residual disease Monitoring Multivariate analysis Neoplasm, Residual Oncogene Proteins, Fusion - genetics Oncology Pathology Patients Pediatrics Peripheral blood Plasma Polymerase Chain Reaction Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality Predictions Prognosis Quantitation Recurrence Risk Risk factors Risk groups Stem cell transplantation |
title | Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction |
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